Search

Your search keyword '"Verhamme P."' showing total 44 results
Start Over Author "Verhamme P." Topic hemorrhage
44 results on '"Verhamme P."'

1. Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients.

Author

Milling TJ Jr, King B, Yue P, Middeldorp S, Beyer-Westendorf J, Eikelboom JW, Crowther M, Xu L, Verhamme P, Siegal DM, and Connolly SJ

Subjects
Aged, Aged, 80 and over, Anticoagulant Reversal Agents adverse effects, Drug Administration Schedule, Europe, Factor Xa adverse effects, Factor Xa Inhibitors adverse effects, Female, Hemorrhage chemically induced, Humans, Male, North America, Prospective Studies, Recombinant Proteins adverse effects, Recurrence, Risk Assessment, Risk Factors, Thrombosis diagnosis, Thrombosis mortality, Time Factors, Treatment Outcome, Anticoagulant Reversal Agents therapeutic use, Anticoagulation Reversal adverse effects, Anticoagulation Reversal mortality, Factor Xa administration & dosage, Factor Xa Inhibitors administration & dosage, Hemorrhage drug therapy, Recombinant Proteins administration & dosage, Thrombosis prevention & control
Abstract

Background: Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior., Objectives: To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death., Methods: This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three., Results: Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001-0.944; p  = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13-62.29; p  = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161-0.915; p  = 0.031)., Conclusion: This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate., Competing Interests: T.J.M.: CSL Behring: consulting; Portola: grant support, steering committee; Octapharma: steering committee. B.K.: none. P.Y.: Portola: employee. S.M.: Daiichi Sankyo, Bayer, Aspen Pharma: grant support; Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Portola: advisory board; Portola: lecture fees; AbbVie: adjudication committee. J.B.-W.: Bayer, Daiichi Sankyo: grant support, lecture fees, advisory board fees; Pfizer: grant support; Portola: lecture fees, advisory board fees. J.W.E.: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Sanofi-Aventis: grant support, honoraria. M.C.: Bristol Myers Squibb Canada, Asahi Kasei, Servier Canada, Precision Biologics, Hemostasis Reference Laboratory, CSL Behring: advisory board; Alexion, Pfizer, CSL Behring, Diagnostica Stago: educational funding; Bayer, Leo Pharma: grant support; Daiichi Sankyo, Bayer, Octapharma: data safety monitoring board. L.X.: None. P.V.: Bayer Healthcare, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Bristol Myers Squibb, Leo Pharma: grant support, consulting, lecture fees; Boehringer Ingelheim: adjudication committee; Anthos, Janssen, Portola: consulting. D.M.S.: Bayer, Bristol Myers Squibb/Pfizer, Servier Canada, Novartis, Leo Pharma, Aspen Pharma, Portola: consulting. S.J.C.: Portola, Bristol Myers Squibb, Bayer, Daiichi Sankyo: grant support, consulting; Javelin: consulting., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Published
2021
Full Text
View/download PDF

2. Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial.

Author

Ockerman A, Miclotte I, Vanhaverbeke M, Vanassche T, Belmans A, Vanhove J, Meyns J, Nadjmi N, Van Hemelen G, Winderickx P, Jacobs R, Politis C, and Verhamme P

Subjects
Administration, Oral, Aged, Aged, 80 and over, Belgium, Double-Blind Method, Female, Humans, Male, Middle Aged, Postoperative Hemorrhage etiology, Prospective Studies, Anticoagulants administration & dosage, Antifibrinolytic Agents therapeutic use, Hemorrhage prevention & control, Postoperative Hemorrhage drug therapy, Tooth Extraction adverse effects, Tranexamic Acid therapeutic use
Abstract

Background: Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs., Methods and Findings: The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash once prior to dental extraction, and thereafter for 3 times a day for 3 days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients' compliance that was based on self-reported information during follow-up., Conclusions: In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted., Trial Registration: ClinicalTrials.gov NCT03413891 EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PV received grants and personal fees from Bayer Healthcare, Boehringer Ingelheim, Pfizer, BMS, Daiichi-Sankyo, Leo Pharma, and Portola and Medtronic outside the submitted work. Other authors have declared that no competing interests exist.

Published
2021
Full Text
View/download PDF

3. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors.

Author

Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, and Milling TJ Jr

Subjects
Acute Disease, Aged, Aged, 80 and over, Atrial Fibrillation drug therapy, Factor Xa Inhibitors metabolism, Factor Xa Inhibitors therapeutic use, Female, Gastrointestinal Hemorrhage chemically induced, Gastrointestinal Hemorrhage drug therapy, Hemorrhage chemically induced, Humans, Intracranial Hemorrhages chemically induced, Intracranial Hemorrhages drug therapy, Male, ROC Curve, Coagulants therapeutic use, Factor Xa therapeutic use, Factor Xa Inhibitors adverse effects, Hemorrhage drug therapy, Recombinant Proteins therapeutic use
Abstract

Background: Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors., Methods: We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin)., Results: Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage., Conclusions: In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.)., (Copyright © 2019 Massachusetts Medical Society.)

Published
2019
Full Text
View/download PDF

4. Management of major bleeding and outcomes in patients treated with direct oral anticoagulants: results from the START-Event registry.

Author

Testa S, Ageno W, Antonucci E, Morandini R, Beyer-Westendorf J, Paciaroni M, Righini M, Sivera P, Verhamme P, Pengo V, Poli D, and Palareti G

Subjects
Administration, Oral, Aged, Aged, 80 and over, Anticoagulants therapeutic use, Atrial Fibrillation drug therapy, Blood Coagulation Factors analysis, Dabigatran pharmacokinetics, Dabigatran therapeutic use, Female, Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Male, Prospective Studies, Pyrazoles pharmacokinetics, Pyrazoles therapeutic use, Pyridones pharmacokinetics, Pyridones therapeutic use, Registries statistics & numerical data, Rivaroxaban pharmacokinetics, Rivaroxaban therapeutic use, Treatment Outcome, Ventricular Fibrillation drug therapy, Anticoagulants pharmacokinetics, Hemorrhage mortality
Abstract

The management of major bleeding in patients treated with direct oral anticoagulants (DOACs) is still not well established. START-Events, a branch of the START registry (Survey on anTicoagulated pAtients RegisTer) (NCT02219984), aims to describe the actual management of bleeding or recurrent thrombotic events in routine clinical practice. We here present the results of the management of bleeding patients. The START-Event registry is a prospective, observational, multicenter, international study. Baseline characteristics (demographic, clinical, risk factors) of patients, laboratory data at admission and during follow-up, site of bleeding, therapeutic strategies, and outcomes at the time of hospital discharge and after 6 months were recorded on a web-based case report form. Between January 2015 and December 2016, 117 patients with major bleeding events were enrolled. Non-valvular atrial fibrillation (NVAF) was the indication for treatment in 84% (62% males); 53 patients had intracranial bleeding (13 fatal), 42 had gastrointestinal bleeding (1 fatal), and 22 had bleeding in other sites. Therapeutic interventions for the management of bleeding were performed in 71% of patients. Therapeutic strategies with/without surgery or invasive procedures included: fluid replacement or red blood cells transfusion, prothrombin complex concentrates (3 or 4 factors), antifibrinolytic drugs, and the administration of idarucizumab. Creatinine, blood cell count, and PT/aPTT were the most frequent tests requested, while specific DOAC measurements were performed in 23% of patients. Mortality during hospitalization was 11.9%, at 6-month follow-up 15.5%. Our data confirm a high heterogeneity in the management of bleeding complications in patients treated with DOACs.

Published
2018
Full Text
View/download PDF

5. Clinical Impact of Bleeding in Cancer-Associated Venous Thromboembolism: Results from the Hokusai VTE Cancer Study.

Author

Kraaijpoel N, Di Nisio M, Mulder FI, van Es N, Beyer-Westendorf J, Carrier M, Garcia D, Grosso M, Kakkar AK, Mercuri MF, Middeldorp S, Hernandez CR, Santamaria A, Schwocho L, Segers A, Verhamme P, Wang TF, Weitz JI, Zhang G, Zwicker JI, Büller HR, and Raskob GE

Subjects
Aged, Anticoagulants administration & dosage, Clinical Decision-Making, Dalteparin administration & dosage, Factor Xa Inhibitors administration & dosage, Female, Hemorrhage diagnosis, Humans, Male, Middle Aged, Neoplasms diagnosis, Patient Selection, Pyridines administration & dosage, Recurrence, Risk Assessment, Risk Factors, Severity of Illness Index, Thiazoles administration & dosage, Time Factors, Treatment Outcome, Venous Thromboembolism diagnosis, Venous Thromboembolism etiology, Anticoagulants adverse effects, Dalteparin adverse effects, Factor Xa Inhibitors adverse effects, Hemorrhage chemically induced, Neoplasms complications, Pyridines adverse effects, Thiazoles adverse effects, Venous Thromboembolism drug therapy
Abstract

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting., Competing Interests: N. Kraaijpoel has nothing to disclose. M. Di Nisio reports personal fees from Daiichi Sankyo. F.I. Mulder has nothing to disclose. N. van Es reports personal fees from Daiichi Sankyo and Pfizer. J. Beyer-Westendorf reports grants and personal fees from Bayer AG, Boehringer-Ingelheim, Daiichi Sankyo, Pfizer and Portola. M. Carrier reports grants from BMS and Leo Pharma, and personal fees from Pfizer, Bayer, Sanofi and Leo Pharma. D. Garcia reports grants and personal fees from Daiichi Sankyo, Janssen and Incyte, and personal fees from BMS and Boehringer-Ingelheim. M. Grosso, M.F. Mercuri, G. Zhang and L. Schwocho are employees of Daiichi Sankyo Inc. A.K. Kakkar reports grants and personal fees from Bayer AG, and personal fees from Boehringer-Ingelheim, Janssen Pharma, Sanofi SA and Verseon. S. Middeldorp reports grants and personal fees from GSK, BMS/Pfizer, Aspen and Daiichi Sankyo, and personal fees from Bayer, Boehringer-Ingelheim, and grants from Sanquin. C. Rojas Hernandez reports personal fees from Daiichi Sankyo. A. Santamaria reports personal fees from Bayer AG, Boehringer-Ingelheim, Pfizer, Bristol-Myers Squibb, Daiichi Sankyo, LeoPharma, Sanofi-Aventis, Rovia and SOBI. A. Segers reports grants from Daiichi Sankyo, IONIS Pharmaceuticals and Janssen Pharmaceuticals. P. Verhamme reports grants and personal fees from Bayer Healthcare, LeoPharma, Daiichi Sankyo and Boehringer-Ingelheim, and personal fees from BMS, Portola, Medscape, Medtronic and Pfizer. T.F. Wang has nothing to disclose. J.I. Weitz reports personal fees from Daiichi-Sankyo, Bayer Healthcare, BMS, Boehringer-Ingelheim, Ionis Pharmaceuticals, Janssen, Johnson and Johnson, Pfizer, Portola, Medscape and Novartis. J.I. Zwicker reports grants from Quercegen and Incyte, and personal fees from Daichii Sankyo and Parexel. H.R. Büller reports personal fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer-Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis and Ionis. G.E. Raskob reports personal fees from Daiichi Sankyo, Itreas, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Isis Pharmaceuticals, Janssen, Pfizer and Portola., (Georg Thieme Verlag KG Stuttgart · New York.)

Published
2018
Full Text
View/download PDF

6. Outpatient Management in Patients with Venous Thromboembolism with Edoxaban: A Post Hoc Analysis of the Hokusai-VTE Study.

Author

Medina A, Raskob G, Ageno W, Cohen AT, Brekelmans MPA, Chen CZ, Grosso MA, Mercuri MF, Segers A, Verhamme P, Vanassche T, Wells PS, Lin M, Winters SM, Weitz JI, and Büller HR

Subjects
Adult, Aged, Ambulatory Care, Anticoagulants adverse effects, Double-Blind Method, Factor Xa Inhibitors adverse effects, Female, Hemorrhage etiology, Humans, Male, Middle Aged, Pyridines adverse effects, Thiazoles adverse effects, United States epidemiology, Venous Thromboembolism epidemiology, Warfarin adverse effects, Anticoagulants therapeutic use, Factor Xa Inhibitors therapeutic use, Hemorrhage epidemiology, Pyridines therapeutic use, Thiazoles therapeutic use, Venous Thromboembolism drug therapy, Warfarin therapeutic use
Abstract

Direct oral anticoagulants (DOACs) facilitate the outpatient treatment of venous thromboembolism (VTE). However, the pivotal trials of DOACs have not reported outcomes separately for patients managed either as outpatients or in the hospital. We performed a subgroup analysis of the Hokusai-VTE study comparing efficacy and safety of edoxaban with warfarin in 8,292 patients with acute VTE. Patients received initial therapy with open-label enoxaparin or unfractionated heparin for ≥5 days in the hospital or as an outpatient at the discretion of the treating physician. Edoxaban or warfarin was then given for 3 to 12 months. The primary efficacy outcome was the cumulative incidence of symptomatic recurrent VTE at 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Of the 5,223 consecutively enrolled patients with recorded hospital status and length of stay, 1,414 patients (27.1%) were managed as outpatients and 3,809 were managed in hospital. Among the outpatients, initial presentation was symptomatic deep-vein thrombosis (DVT) in 1,183 patients (83.7%) and pulmonary embolism (PE) in 231 patients (16.3%). Among the outpatients with DVT, recurrent VTE occurred in 18 (3.0%) given edoxaban and in 21 (3.6%) given warfarin (risk difference: −0.61, 95% confidence interval [CI]: −2.6 to 1.4). The principal safety outcome in outpatients occurred in 46 edoxaban patients (7.7%) and in 48 warfarin patients (8.3%; risk difference: −0.59, 95% CI: −3.7 to 2.5). Most outpatients had symptomatic DVT at presentation. In these patients, initial heparin followed by edoxaban had similar efficacy and safety to standard therapy with heparin and warfarin., Competing Interests: Declaration of Interests: Dr. Raskob reports personal fees from Daiichi Sankyo and Itreas during the conduct of the study and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Isis Pharmaceuticals, Janssen, Pfizer and Portola outside the submitted work. Dr. Ageno reports grants, personal fees and non-financial support from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Stago, and personal fees from Bristol-Myers Squibb, Pfizer and Ono, outside the submitted work. Dr. Cohen reports grants from Daiichi Sankyo Pharma Development during the conduct of the study; grants and personal fees from Bayer, Bristol-Myers Squibb and Pfizer; and personal fees from Boehringer Ingelheim, Janssen, Johnson & Johnson, Portola, Sanofi, and XO1 outside the submitted work. Dr. Chen is an employee of Daiichi Sankyo, Inc. Dr. Grosso and Dr. Lin are employees of Daiichi Sankyo Pharma Development. Dr. Mercuri is an employee of Daiichi Sankyo Pharma Development and has a patent application pending for properties of edoxaban. Dr. Segers reports grants from Daiichi Sankyo Pharma Development during the conduct of the study and grants from Isis Pharmaceuticals outside the submitted work. Dr. Verhamme reports grants and personal fees from Daiichi-Sankyo Pharma Development during the conduct of the study and grants from Leo Pharma; grants and personal fees from Boehringer Ingelheim, Sanofi and ThromboGenics; and personal fees from Bayer outside the submitted work. Dr. Wells reports personal fees from Bayer and Daiichi Sankyo and grants from Bristol-Myers Squibb and Pfizer outside the submitted work. Ms. Winters was an employee of Daiichi Sankyo, Inc. Dr. Weitz reports personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Isis Pharmaceuticals, Janssen, Pfizer and Portola outside the submitted work. Dr. Büller reports grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Isis Pharmaceuticals, Pfizer, Roche, Sanofi and Thrombogenics outside the submitted work. Dr. Medina, Dr., Brekelmans and Dr. Vanassche have nothing to disclose.

Published
2017
Full Text
View/download PDF

7. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

Author

Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, and Weitz JI

Subjects
Adult, Aged, Aged, 80 and over, Antibodies blood, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized immunology, Anticoagulants adverse effects, Blood Coagulation drug effects, Dabigatran adverse effects, Dabigatran blood, Drug Hypersensitivity, Female, Hemorrhage chemically induced, Humans, Infusions, Intravenous, Male, Middle Aged, Prospective Studies, Thrombin Time, Thrombosis chemically induced, Time Factors, Antibodies, Monoclonal, Humanized therapeutic use, Dabigatran antagonists & inhibitors, Hemorrhage drug therapy
Abstract

Background: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran., Methods: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures., Results: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals., Conclusions: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .).

Published
2017
Full Text
View/download PDF

8. Venous thromboembolism in centenarians: Findings from the RIETE registry.

Author

Lacruz B, Tiberio G, Núñez MJ, López-Jiménez L, Riera-Mestre A, Tiraferri E, Verhamme P, Mazzolai L, González J, and Monreal M

Subjects
Aged, 80 and over, Anemia epidemiology, Comorbidity, Female, Heart Failure epidemiology, Heparin, Low-Molecular-Weight therapeutic use, Humans, Male, Pulmonary Embolism epidemiology, Recurrence, Renal Insufficiency epidemiology, Spain epidemiology, Treatment Outcome, Venous Thromboembolism epidemiology, Venous Thrombosis epidemiology, Warfarin therapeutic use, Anticoagulants therapeutic use, Hemorrhage chemically induced, Pulmonary Embolism drug therapy, Registries, Venous Thromboembolism drug therapy, Venous Thrombosis drug therapy
Abstract

Background: The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain., Methods: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years., Results: Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported., Conclusions: Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Published
2016
Full Text
View/download PDF

9. Managing reversal of direct oral anticoagulants in emergency situations. Anticoagulation Education Task Force White Paper.

Author

Ageno W, Büller HR, Falanga A, Hacke W, Hendriks J, Lobban T, Merino J, Milojevic IS, Moya F, van der Worp HB, Randall G, Tsioufis K, Verhamme P, and Camm AJ

Subjects
Administration, Oral, Advisory Committees, Dabigatran, Factor Xa Inhibitors, Humans, Rivaroxaban, Antibodies, Monoclonal, Humanized therapeutic use, Anticoagulants adverse effects, Hemorrhage drug therapy
Abstract

Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

Published
2016
Full Text
View/download PDF

10. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

Author

Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, and Crowther M

Subjects
Acute Disease, Aged, Aged, 80 and over, Cardiovascular Diseases complications, Enoxaparin adverse effects, Factor Xa adverse effects, Factor Xa Inhibitors metabolism, Factor Xa Inhibitors therapeutic use, Female, Gastrointestinal Hemorrhage chemically induced, Gastrointestinal Hemorrhage drug therapy, Hemorrhage chemically induced, Humans, Infusions, Intravenous, Intracranial Hemorrhages chemically induced, Intracranial Hemorrhages diagnosis, Intracranial Hemorrhages drug therapy, Male, Prospective Studies, Pyrazoles adverse effects, Pyridones adverse effects, Recombinant Proteins adverse effects, Rivaroxaban adverse effects, Thrombosis etiology, Factor Xa therapeutic use, Factor Xa Inhibitors adverse effects, Hemorrhage drug therapy, Recombinant Proteins therapeutic use
Abstract

Background: Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers., Methods: In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication., Results: The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up., Conclusions: On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Published
2016
Full Text
View/download PDF

11. Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE study.

Author

Raskob G, Ageno W, Cohen AT, Brekelmans MP, Grosso MA, Segers A, Meyer G, Verhamme P, Wells PS, Lin M, Winters SM, Weitz JI, and Büller HR

Subjects
Adult, Aged, Anticoagulants, Comparative Effectiveness Research, Double-Blind Method, Female, Follow-Up Studies, Hemorrhage mortality, Heparin therapeutic use, Humans, Male, Middle Aged, Pulmonary Embolism epidemiology, Recurrence, Risk Assessment, Venous Thromboembolism complications, Venous Thromboembolism drug therapy, Venous Thromboembolism epidemiology, Ventricular Dysfunction, Right complications, Hemorrhage chemically induced, Pulmonary Embolism prevention & control, Pyridines adverse effects, Pyridines therapeutic use, Secondary Prevention methods, Thiazoles adverse effects, Thiazoles therapeutic use, Venous Thromboembolism prevention & control, Warfarin adverse effects, Warfarin therapeutic use
Abstract

Background: There are few data on the relative efficacy and safety of direct oral anticoagulants, such as edoxaban, compared with vitamin K antagonists during extended therapy for venous thromboembolism. This analysis evaluates the risk-benefit of extended treatment for up to 12 months with edoxaban compared with warfarin among patients enrolled in the Hokusai-VTE study who continued therapy beyond 3 months., Methods: The Hokusai-VTE trial (NCT00986154) was a randomised, double-blind, event driven non-inferiority trial in 8292 patients comparing edoxaban with warfarin in the treatment of patients with acute venous thromboembolism. All patients were treated for at least 3 months and treatment was continued for up to 12 months. The outcomes at 12 months were documented in all patients irrespective of treatment duration. 3633 patients treated with edoxaban and 3594 treated with warfarin who completed 3 months of treatment were eligible for this analysis. The primary efficacy outcome was the incidence of adjudicated symptomatic recurrent venous thromboembolism evaluated for each of the time intervals of 3 months, greater than 3 months to 6 months, greater than 6 months to less than 12 months, and at 12 months, as well as the cumulative incidence occurring between 3 and 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Both on-treatment and intention-to-treat analyses were done., Findings: In the on-treatment analysis, the incidence of recurrent venous thromboembolism at 3 months was 1·1% (0·8-1·4; 44 of 4118 patients) in the edoxaban-treated group versus 1·2% (0·9-1·6; 51 of 4122) in the warfarin-treated group; between greater than 3 months and 6 months, 0·7% (0·3-1·5; eight of 1076) versus 0·5% (0·2-1·1; five of 1084); between greater than 6 months and less than 12 months, 0·2% (0·0-0·8; two of 896) versus 0·8% (0·03-1·7; seven of 851); and at 12 months, <0·1% (0·0-0·3; one of 1661) versus 0·1% (0·0-0·4; two of 1659). In the on-treatment analysis, the cumulative incidence of recurrent venous thromboembolism between 3 and 12 months was 0·3% (95% CI 0·2-1·5; 11 of 3633 patients) in the edoxaban-treated group and 0·4% (0·2-1·7; 14 of 3594) in the warfarin-treated group (HR 0·78, 95% CI 0·36-1·72). The cumulative incidence of clinically relevant bleeding (major or non-major) between 3 and 12 months was 3·9% (95% CI 3·3-4·6; 143 of 3633 patients) in the edoxaban-treated group and 4·1% (3·5-4·8; 147 of 3594 patients) in the warfarin-treated group (HR 0·97, 95% CI 0·77-1·22); cumulative incidence of major bleeding was 0·3% (95% CI 0·2-0·5; 11 of 3633 patients) in the edoxaban-treated group and 0·7% (0·4-1·0; 24 of 3594 patients) in the warfarin-treated group (HR 0·45, 95% CI 0·22-0·92). Similar results were obtained in the intention-to-treat analysis., Interpretation: Extended treatment with edoxaban is effective and associated with less major bleeding than warfarin. Edoxaban once daily provides an attractive alternative to warfarin for patients with venous thromboembolism who require extended treatment for prevention of recurrent venous thromboembolism., Funding: Daiichi Sankyo., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
Full Text
View/download PDF

12. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH.

Author

Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, and Weitz JI

Subjects
Administration, Oral, Antibodies, Monoclonal, Humanized therapeutic use, Anticoagulants administration & dosage, Antidotes adverse effects, Antidotes pharmacokinetics, Arginine analogs & derivatives, Arginine therapeutic use, Coagulants adverse effects, Coagulants pharmacokinetics, Factor Xa therapeutic use, Hemorrhage chemically induced, Humans, Piperazines therapeutic use, Recombinant Proteins therapeutic use, Anticoagulants adverse effects, Antidotes therapeutic use, Blood Coagulation drug effects, Coagulants therapeutic use, Hemorrhage drug therapy
Published
2016
Full Text
View/download PDF

13. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.

Author

Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, and Kirchhof P

Subjects
Administration, Oral, Anticoagulants adverse effects, Coronary Artery Disease complications, Electric Countershock adverse effects, Europe, Humans, Language, Renal Insufficiency, Chronic complications, Societies, Medical, Anticoagulants administration & dosage, Anticoagulants classification, Atrial Fibrillation drug therapy, Hemorrhage chemically induced, Stroke prevention & control
Abstract

The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Published
2015
Full Text
View/download PDF

14. Long-term Clinical Outcomes of Splanchnic Vein Thrombosis: Results of an International Registry.

Author

Ageno W, Riva N, Schulman S, Beyer-Westendorf J, Bang SM, Senzolo M, Grandone E, Pasca S, Di Minno MN, Duce R, Malato A, Santoro R, Poli D, Verhamme P, Martinelli I, Kamphuisen P, Oh D, D'Amico E, Becattini C, De Stefano V, Vidili G, Vaccarino A, Nardo B, Di Nisio M, and Dentali F

Subjects
Adult, Female, Follow-Up Studies, Humans, Liver Cirrhosis complications, Male, Middle Aged, Prospective Studies, Recurrence, Venous Thrombosis complications, Venous Thrombosis mortality, Anticoagulants adverse effects, Hemorrhage chemically induced, Registries, Splanchnic Circulation, Venous Thrombosis therapy
Abstract

Importance: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT)., Objective: To assess the incidence rates of bleeding, thrombotic events, and mortality in a large international cohort of patients with SVT., Design, Setting, and Participants: A prospective cohort study was conducted beginning May 2, 2008, and completed January 30, 2014, at hospital-based centers specialized in the management of thromboembolic disorders; a 2-year follow-up period was completed January 30, 2014, and data analysis was conducted from July 1, 2014, to February 28, 2015. Participants included 604 consecutive patients with objectively diagnosed SVT; there were no exclusion critieria. Information was gathered on baseline characteristics, risk factors, and antithrombotic treatment. Clinical outcomes during the follow-up period were documented and reviewed by a central adjudication committee., Main Outcomes and Measures: Major bleeding, defined according to the International Society on Thrombosis and Hemostasis; bleeding requiring hospitalization; thrombotic events, including venous and arterial thrombosis; and all-cause mortality., Results: Of the 604 patients (median age, 54 years; 62.6% males), 21 (3.5%) did not complete follow-up. The most common risk factors for SVT were liver cirrhosis (167 of 600 patients [27.8%]) and solid cancer (136 of 600 [22.7%]); the most common sites of thrombosis were the portal vein (465 of 604 [77.0%]) and the mesenteric veins (266 of 604 [44.0%]). Anticoagulation was administered to 465 patients in the entire cohort (77.0%) with a mean duration of 13.9 months; 175 of the anticoagulant group (37.6%) received parenteral treatment only, and 290 patients (62.4%) were receiving vitamin K antagonists. The incidence rates (reported with 95% CIs) were 3.8 per 100 patient-years (2.7-5.2) for major bleeding, 7.3 per 100 patient-years (5.8-9.3) for thrombotic events, and 10.3 per 100 patient-years (8.5-12.5) for all-cause mortality. During anticoagulant treatment, these rates were 3.9 per 100 patient-years (2.6-6.0) for major bleeding and 5.6 per 100 patient-years (3.9-8.0) for thrombotic events. After treatment discontinuation, rates were 1.0 per 100 patient-years (0.3-4.2) and 10.5 per 100 patient-years (6.8-16.3), respectively. The highest rates of major bleeding and thrombotic events during the whole study period were observed in patients with cirrhosis (10.0 per 100 patient-years [6.6-15.1] and 11.3 per 100 patient-years [7.7-16.8], respectively); the lowest rates were in patients with SVT secondary to transient risk factors (0.5 per 100 patient-years [0.1-3.7] and 3.2 per 100 patient-years [1.4-7.0], respectively)., Conclusions and Relevance: Most patients with SVT have a substantial long-term risk of thrombotic events. In patients with cirrhosis, this risk must be balanced against a similarly high risk of major bleeding. Anticoagulant treatment appears to be safe and effective in most patients with SVT.

Published
2015
Full Text
View/download PDF

15. Idarucizumab for Dabigatran Reversal.

Author

Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, and Weitz JI

Subjects
Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized blood, Benzimidazoles adverse effects, Benzimidazoles blood, Blood Coagulation drug effects, Dabigatran, Female, Hemorrhage chemically induced, Humans, Infusions, Intravenous, Male, Middle Aged, Prospective Studies, Thrombosis chemically induced, Thrombosis epidemiology, beta-Alanine adverse effects, beta-Alanine antagonists & inhibitors, beta-Alanine blood, Antibodies, Monoclonal, Humanized administration & dosage, Anticoagulants adverse effects, Anticoagulants blood, Benzimidazoles antagonists & inhibitors, Hemorrhage drug therapy, beta-Alanine analogs & derivatives
Abstract

Background: Specific reversal agents for non-vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran., Methods: We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. A key secondary end point was the restoration of hemostasis., Results: This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated., Conclusions: Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.).

Published
2015
Full Text
View/download PDF

16. A RIETE registry analysis of recurrent thromboembolism and hemorrhage in patients with catheter-related thrombosis.

Author

Baumann Kreuziger L, Cote L, Verhamme P, Greenberg S, Caprini J, Muñoz FJ, Valle R, and Monreal Bosch M

Subjects
Catheters adverse effects, Humans, Recurrence, Registries, Thrombosis therapy, Hemorrhage etiology, Pulmonary Embolism etiology, Venous Thrombosis etiology
Abstract

Background: Few studies have investigated the treatment and the outcomes of patients with catheter-related thrombosis (CRT)., Methods: The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of consecutive patients with objectively confirmed venous thromboembolism (VTE). We analyzed the characteristics, treatment, and outcomes of patients with CRT., Results: Of 558 patients with CRT, 45 (8%) presented with a pulmonary embolism (PE) concomitantly. More patients had central line-associated thrombosis compared with port systems, but catheter type did not influence the risk of presenting with a PE. Patients with only CRT were more often prescribed low-molecular-weight heparin for the duration of their anticoagulant treatment compared with patients presenting with concomitant PE. VTE recurrences and major bleeding events occurred frequently during treatment with anticoagulation (7 per 100 patient-years and 8.9 per 100 patient years, respectively). The rates of fatal PE recurrences (1.85 per 100 patient-years) and fatal bleeding (2.32 per 100 patient-years) were similar. Patients with an additional transient risk factor for VTE had the lowest risk for VTE recurrences (odds ratio [OR], 0.07; 90% confidence interval [CI], 0.01-0.45) compared with patients with CRT and no additional transient risk factors. PE at presentation increased the risk of recurrent thrombosis by 2.4 times. Renal insufficiency was also an independent predictor of recurrent thrombosis (OR, 3.93; 90% CI, 2.0-7.7). The odds of recurrent thrombosis was decreased by 77% in patients who received anticoagulation therapy for >90 days compared with patients with a shorter treatment (OR, 0.23; 90% CI, 0.1-0.56)., Conclusions: Concomitant PE occurs less frequently in CRT than lower extremity deep venous thrombosis, but it is associated with a worse outcome. CRT occurs in high-risk patients, and duration of anticoagulation must be predicated on balancing these risks., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Published
2015
Full Text
View/download PDF

17. Gender differences in cancer patients with acute venous thromboembolism.

Author

Martín-Martos F, Trujillo-Santos J, Barrón M, Vela J, Javier Marchena P, Braester A, Hij A, Hernández-Blasco L, Verhamme P, and Manuel M

Subjects
Acute Disease, Aged, Comorbidity, Female, Humans, Incidence, Male, Risk Factors, Sex Characteristics, Sex Distribution, Spain epidemiology, Survival Rate, Treatment Outcome, Anticoagulants therapeutic use, Hemorrhage mortality, Neoplasms mortality, Venous Thromboembolism drug therapy, Venous Thromboembolism mortality
Abstract

Background: The outcome of cancer patients with acute venous thromboembolism (VTE) may differ according to gender., Methods: We used the RIETE database to compare the rate of VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) recurrences), major bleeding and mortality during the course of anticoagulation, according to gender., Results: As of August 2014, 11,055 patients with active cancer were enrolled in RIETE, of whom 5,104 (46%) were women. During the course of anticoagulation (mean: 142 days), 505 patients developed recurrent VTE, 429 bled and 2730 died. Compared with men, women had a significantly lower rate of fatal bleeding (risk ratio [RR]: 0.69; 95% CI: 0.47-0.99) and death (RR: 0.90; 95% CI: 0.83-0.97), and a non-significantly lower rate of PE recurrences (RR 0.83; 95% CI: 0.65-1.06) and major bleeding (RR: 0.89; 95% CI: 0.74-1.08)., Conclusions: During the course of anticoagulation, cancer women with VTE had a better outcome than men., (© 2015 Elsevier Ltd. All rights reserved.)

Published
2015
Full Text
View/download PDF

18. Monitoring and reversal strategies for new oral anticoagulants.

Author

Vanden Daelen S, Peetermans M, Vanassche T, Verhamme P, and Vandermeulen E

Subjects
Animals, Anticoagulants adverse effects, Hemorrhage chemically induced, Humans, Administration, Oral, Anticoagulants therapeutic use, Atrial Fibrillation drug therapy, Blood Coagulation drug effects, Hemorrhage drug therapy, Venous Thromboembolism drug therapy
Abstract

Thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban, apixaban and edoxaban form a new class of non-vitamin K antagonist oral anticoagulants and have been extensively studied in patients with venous thromboembolism and atrial fibrillation. They offer anticoagulation that is as effective and at least as safe compared to warfarin without the need for routine laboratory monitoring; however, no reversal strategies are currently validated in case of a non-vitamin K antagonist oral anticoagulant-associated bleed. In emergency situations, laboratory drug measurement and well-defined management for non-vitamin K antagonist oral anticoagulant-induced hemorrhage may improve clinical outcome. In this review, the merits and limitations of the routine coagulation tests and some of the more specific laboratory assays are compared. Furthermore, prohemostatic measures are reviewed and the recommended strategies in case of bleeding are summarized. Specific reversal agents are currently under development (idarucizumab for dabigatran, andexanet alfa for Xa inhibitors, and PER977 for both Xa- and thrombin inhibitors), which will facilitate clinical management of severe bleeding and emergency surgery.

Published
2015
Full Text
View/download PDF

19. Direct oral anticoagulants for acute venous thromboembolism: closing the circle?

Author

Verhamme P and Bounameaux H

Subjects
Dabigatran, Female, Humans, Male, beta-Alanine administration & dosage, Anticoagulants administration & dosage, Antithrombins administration & dosage, Benzimidazoles administration & dosage, Hemorrhage chemically induced, Venous Thromboembolism drug therapy, Warfarin administration & dosage, beta-Alanine analogs & derivatives
Published
2014
Full Text
View/download PDF

20. Obesity in haemophilia patients: effect on bleeding frequency, clotting factor concentrate usage, and haemostatic and fibrinolytic parameters.

Author

Tuinenburg A, Biere-Rafi S, Peters M, Verhamme P, Peerlinck K, Kruip MJ, Laros-Van Gorkom BA, Roest M, Meijers JC, Kamphuisen PW, and Schutgens RE

Subjects
Case-Control Studies, Cross-Sectional Studies, Fibrinolysis, Hemophilia A complications, Hemorrhage complications, Hemostasis, Humans, Male, Middle Aged, Obesity complications, Blood Coagulation Factors administration & dosage, Hemophilia A blood, Hemorrhage blood, Obesity blood
Abstract

The prevalence of obesity in patients with haemophilia (PWH) is increasing. We investigated the effect of obesity on bleeding frequency and clotting factor concentrate (CFC) usage in PWH and assessed whether prothrombotic changes observed in obesity differ between controls and PWH. Number of bleeds and CFC usage were compared between obese (N = 51) and non-obese (N = 46) haemophilia A patients. Markers of haemostasis and fibrinolysis were compared between PWH, and gender-, age- and body mass index (BMI)-matched non-haemophilic controls (N = 91). Median number of bleeds/patient-month was comparable between obese and non-obese patients with severe haemophilia (P = 0.791). Obese patients with severe haemophilia used 1.4 times more CFC/patient-month than non-obese patients (P = 0.036). When adjusting for weight this difference disappeared (P = 0.451). von Willebrand factor plasma concentration (VWF:Ag), factor VIII activity and endogenous thrombin potential were higher in obese than in non-obese controls. Obesity did not influence these markers in PWH. Plasminogen activator inhibitor type 1 levels were higher in obese vs. non-obese PWH (P < 0.001), whereas levels were comparable between PWH and controls (P = 0.912). Plasmin-α2-antiplasmin complex (PAP) levels appeared to be lower in obese vs. non-obese subjects, both within controls (P = 0.011) and PWH (P = 0.008). However, in PWH, PAP levels were higher than in controls (P < 0.001). Obesity is associated with an increase in net CFC usage in PWH, but has no effect on bleeding frequency. In addition, obesity attenuates hyperfibrinolysis in PWH. Future research investigating whether obese PWH need CFC treatment dosed on weight or whether a lower dosage would suffice to prevent and treat bleedings is needed., (© 2013 John Wiley & Sons Ltd.)

Published
2013
Full Text
View/download PDF

21. Soft tissue bleeding associated with antithrombotic treatment: technical and clinical outcomes after transcatheter embolization.

Author

Maleux G, Van Sonhoven F, Hofkens PJ, Laenen A, Cappelle S, Vaninbroukx J, Heye S, and Verhamme P

Subjects
Adult, Aged, Aged, 80 and over, Connective Tissue Diseases diagnostic imaging, Female, Fibrinolytic Agents therapeutic use, Hemorrhage diagnostic imaging, Humans, Male, Middle Aged, Radiography, Retrospective Studies, Treatment Outcome, Young Adult, Catheterization, Peripheral methods, Connective Tissue Diseases chemically induced, Connective Tissue Diseases drug therapy, Embolization, Therapeutic methods, Fibrinolytic Agents adverse effects, Hemorrhage chemically induced, Hemorrhage drug therapy
Abstract

Purpose: To assess retrospectively technical and clinical outcomes after transcatheter embolization in patients presenting with soft tissue bleeding associated with antithrombotic therapy and to determine factors potentially affecting the clinical outcomes after embolization., Materials and Methods: There were 42 patients who underwent embolization for soft tissue bleeding associated with antithrombotic therapy. Principal clinical symptoms were hemodynamic shock (n = 21), abdominal pain (n = 9), back pain (n = 7), and buttock or thigh pain (n = 5). Ultrasound or computed tomography (CT) or both were performed in 40 patients (95%); 2 patients (5%) were immediately referred for angiography. Several laboratory and radiographic factors were analyzed to determine if any influenced the clinical outcome., Results: A hematoma was identified in the anterior abdominal wall (n = 18 [43%]), in the retroperitoneum (n = 18 [43%]), or in the thigh or gluteal region (n = 6 [14%]). Embolization was successful in all patients; early recurrent bleeding with a fatal outcome was recorded in one patient (2%). In nine patients (22%), secondary surgical drainage of the hematoma was performed to manage a compartment syndrome. During follow-up (mean, 37.9 months; range, 0.03-85.28 months), 11 patients (26%) died; death was related to the bleeding in 6 patients (14%). Both activated partial thromboplastin time (aPTT) and prothrombin time (PT) were correlated with hematoma size. Prolonged aPTT before embolization was associated with a higher risk of bleeding-related mortality (P = .04)., Conclusions: Transcatheter embolization was very effective in stopping soft tissue bleeding associated with antithrombotic therapy. However, there was still considerable morbidity and mortality after successful embolization. aPTT prolongation emerged as a risk factor for bleeding-related deaths., (Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.)

Published
2012
Full Text
View/download PDF

22. Heparin-coated polyacrylonitrile membrane versus regional citrate anticoagulation: a prospective randomized study of 2 anticoagulation strategies in patients at risk of bleeding.

Author

Evenepoel P, Dejagere T, Verhamme P, Claes K, Kuypers D, Bammens B, and Vanrenterghem Y

Subjects
Adult, Aged, Female, Hemorrhage epidemiology, Humans, Male, Middle Aged, Prospective Studies, Renal Dialysis adverse effects, Risk Factors, Acrylic Resins administration & dosage, Anticoagulants administration & dosage, Citric Acid administration & dosage, Hemorrhage prevention & control, Heparin administration & dosage, Membranes, Artificial
Abstract

Background: Hemodialysis requires anticoagulation to prevent clotting of the extracorporeal circuit. Systemic anticoagulation with heparin is contraindicated in patients at high risk of bleeding. In these patients, regional citrate anticoagulation (RCA), with either calcium-free (RCA-Ca0) or calcium-containing dialysate (RCA-Ca3.0), and heparin-coated membranes (1.3 m(2); AN69ST; Nephral 300ST, Gambro-Hospal, Meyzieu, France) may represent valid alternatives., Methods: To compare the efficacy and safety of these regional anticoagulation modalities, we performed a prospective randomized trial including 33 hemodialysis patients at high risk of bleeding. Regional anticoagulation was achieved by means of either AN69ST (11 patients, 31 sessions), RCA-Ca0 (11 patients, 32 sessions), or RCA-Ca3.0 (11 patients, 30 sessions). Patients assigned to RCA were dialyzed using a polysulfone membrane (1.3 m(2); F60; Fresenius Medical Care, Bad Homburg, Germany). Scheduled dialysis time was 4 hours. At the end of each dialysis session, the dialyzer was inspected for visible signs of thrombus formation and scored semiquantitatively (0, no clotting, to 4, severe clotting). Solute clearances were monitored at the second and fourth treatment hour as a parameter of subclinical clotting of the dialyzer., Results: Clotting phenomena necessitating premature termination of the dialysis session were encountered in 39%, 13%, and 0% using AN69ST, RCA-Ca3.0, and RCA-Ca0, respectively (P < 0.005). All clotting with AN69ST occurred after the second treatment hour. Mean dialyzer clotting scores were 2.7, 1.5, and 1.1, respectively (P < 0.0001). Significantly greater instantaneous urea nitrogen clearances were achieved at 2 hours during RCA compared with AN69ST. Except for clotting phenomena, no adverse events were observed., Conclusion: Citrate provides superior regional anticoagulation compared with AN69ST membranes.

Published
2007
Full Text
View/download PDF

23. Edoxaban for the Long‐Term Therapy of Venous Thromboembolism: Should the Criteria for Dose Reduction be Revised?

Author

Camporese, G., Simioni, P., Di Micco, P., Fernandez-Capitan, C., Rivas, A., Font, C., Sahuquillo, J. C., Villares, P., Prandoni, P., Monreal, M., Adarraga, M. D., Agud, M., Aibar, J., Aibar, M. A., Alfonso, J., Amado, C., Arcelus, J. I., Baeza, C., Ballaz, A., Barba, R., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Camon, A. M., Castro, J., Caudevilla, M. A., Cerda, P., Chasco, L., Criado, J., de Ancos, C., de Miguel, J., del Toro, J., Demelo-Rodriguez, P., Diaz-Peromingo, J. A., Diez-Sierra, J., Dominguez, I. M., Encabo, M., Escribano, J. C., Falga, C., Farfan, A. I., Fernandez de Roitegui, K., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia-Mullor, M. M., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Jou, I., Lacruz, B., Lalueza, A., Lecumberri, R., Lima, J., Lobo, J. L., Lopez-Brull, H., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Baquerizo, C., Mella, C., Mellado, M., Mercado, M. I., Moises, J., Morales, M. V., Munoz-Blanco, A., Munoz-Guglielmetti, D., Munoz-Rivas, N., Nart, E., Nieto, J. A., Nunez, M. J., Olivares, M. C., Ortega-Recio, M. D., Osorio, J., Otalora, S., Otero, R., Paredes, D., Parra, P., Parra, V., Pedrajas, J. M., Pellejero, G., Peris, M. L., Pesantez, D., Porras, J. A., Portillo, J., Ramos, E., Reig, L., Riera-Mestre, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rogado, J., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Gimenez, N., Ruiz-Ruiz, J., Ruiz-Sada, P., Salgueiro, G., Samperiz, A., Sanchez-Munoz-Torrero, J. F., Sancho, T., Siguenza, P., Sirisi, M., Soler, S., Suarez, S. Surinach J. M., Tiberio, G., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J. R., Vidal, G., Vilar, C., Zamora, C., Gutierrez, P., Vazquez, F. J., Vanassche, T., Vandenbriele, C., Verhamme, P., Hirmerova, J., Maly, R., Salgado, E., Benzidia, I., Bertoletti, L., Bura-Riviere, A., Crichi, B., Debourdeau, P., Espitia, O., Farge-Bancel, D., Helfer, H., Mahe, I., Moustafa, F., Poenou, G., Schellong, S., Braester, A., Brenner, B., Tzoran, I., Amitrano, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., Colaizzo, D., Dentali, F., Giammarino, E., Grandone, E., Mangiacapra, S., Mastroiacovo, D., Maida, R., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Make, K., Meilanden, K., Skride, A., Ferreira, M., Fonseca, S., Martins, F., Meireles, J., Bosevski, M., Zdraveska, M., Bounameaux, H., Mazzolai, L., Caprini, J. A., Tafur, A. J., Weinberg, I., Wilkins, H., Bui, H. M., and UAM. Departamento de Medicina

Subjects
Male, medicine.medical_specialty, Time Factors, Dose, Medicina, Pyridines, Hemorrhage, General Biochemistry, Genetics and Molecular Biology, Article, chemistry.chemical_compound, Edoxaban, Recurrence, Internal medicine, medicine, Humans, Prospective Studies, Registries, General Pharmacology, Toxicology and Pharmaceutics, Long term therapy, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Drug Tapering, business.industry, lcsh:Public aspects of medicine, General Neuroscience, Mortality rate, Research, lcsh:RM1-950, Hazard ratio, Anticoagulants, lcsh:RA1-1270, General Medicine, Articles, Venous Thromboembolism, Middle Aged, Confidence interval, Thiazoles, lcsh:Therapeutics. Pharmacology, chemistry, Practice Guidelines as Topic, Dose reduction, Female, business, Venous thromboembolism, Follow-Up Studies
Abstract

Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated., No funding was received for this work

Published
2020

24. Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism

Author

Martinez-Urbistondo D., de la Garza R. G., Villares-Fernandez P., Font C., Schellong S., Lopez-Nunez J. J., Gil-Diaz A., del Carmen Diaz-Pedroche M., Hirmerova J., Monreal M., Adarraga M., Aibar J., Alonso J., Amado C., Arcelus J., Asuero A., Ballaz A., Barba R., Barbagelata C., Barron M., Barron-Andres B., Blanco-Molina A., Beddar Chaib F., Botella E., Castro J., Chasco L., Criado J., de Ancos C., del Toro J., Demelo-Rodriguez P., Diaz-Brasero A., Diaz-Pedroche M., Diaz-Peromingo J., Di Campli M., Dubois-Silva A., Escribano J., Esposito F., Farfan-Sedano A., Fernandez-Capitan C., Fernandez-Reyes J., Fidalgo M., Flores K., Font L., Francisco I., Gabara C., Galeano-Valle F., Garcia M., Garcia-Bragado F., Garcia de Herreros M., de la Garza R., Garcia-Diaz C., Gomez-Cuervo C., Grau E., Guirado L., Gutierrez J., Hernandez-Blasco L., Jara-Palomares L., Jaras M., Jimenez D., Jimenez R., Jimenez-Alfaro C., Joya M., Lainez-Justo S., Lalueza A., Latorre A., Lima J., Lobo J., Lopez-Jimenez L., Lopez-Miguel P., Lopez-Nunez J., Lopez-Reyes R., Lopez-Saez J., Lorenzo A., Madridano O., Maestre A., Marchena P., Martin del Pozo M., Martin-Martos F., Mella C., Mercado M., Moises J., Munoz-Blanco A., Nieto J., Nofuentes-Perez E., Nunez-Fernandez M., Olid-Velilla M., Olivares M., Osorio J., Otalora S., Otero R., Paredes D., Pedrajas J., Porras J., Portillo J., Redondo I., Rodriguez-Matute C., Rosa V., Ruiz-Artacho P., Ruiz-Ruiz J., Salgueiro G., Sanchez-Martinez R., Sanchez-Munoz-Torrero J., Sancho T., Soler S., Suarez-Rodriguez B., Surinach J., Torres M., Torres-Sanchez A., Tolosa C., Trujillo-Santos J., Uresandi F., Valero B., Valle R., Varona J., Vela L., Vela J., Vidal G., Villalobos A., Villares P., Zamora C., Ay C., Nopp S., Pabinger I., Engelen M., Vanassche T., Verhamme P., Maly R., Accassat S., Ait Abdallah N., Bertoletti L., Bura-Riviere A., Catella J., Couturaud F., Crichi B., Debourdeau P., Espitia O., Farge-Bancel D., Grange C., Helfer H., Lacut K., Le Mao R., Mahe I., Morange P., Moustafa F., Poenou G., Sarlon-Bartoli G., Suchon P., Quere I., Braester A., Brenner B., Kenet G., Tzoran I., Basaglia M., Bilora F., Bortoluzzi C., Brandolin B., Ciammaichella M., De Angelis A., Di Micco P., Imbalzano E., Merla S., Pesavento R., Prandoni P., Siniscalchi C., Tufano A., Visona A., Vo Hong N., Zalunardo B., Nishimoto Y., Sato Y., Make K., Skride A., Strautmane S., Fonseca S., Martins F., Meireles J., Bosevski M., Bounameaux H., Mazzolai L., Caprini J., Bui H., Martinez-Urbistondo, D., de la Garza, R. G., Villares-Fernandez, P., Font, C., Schellong, S., Lopez-Nunez, J. J., Gil-Diaz, A., del Carmen Diaz-Pedroche, M., Hirmerova, J., Monreal, M., Adarraga, M., Aibar, J., Alonso, J., Amado, C., Arcelus, J., Asuero, A., Ballaz, A., Barba, R., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Beddar Chaib, F., Botella, E., Castro, J., Chasco, L., Criado, J., de Ancos, C., del Toro, J., Demelo-Rodriguez, P., Diaz-Brasero, A., Diaz-Pedroche, M., Diaz-Peromingo, J., Di Campli, M., Dubois-Silva, A., Escribano, J., Esposito, F., Farfan-Sedano, A., Fernandez-Capitan, C., Fernandez-Reyes, J., Fidalgo, M., Flores, K., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M., Garcia-Bragado, F., Garcia de Herreros, M., de la Garza, R., Garcia-Diaz, C., Gomez-Cuervo, C., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M., Jimenez, D., Jimenez, R., Jimenez-Alfaro, C., Joya, M., Lainez-Justo, S., Lalueza, A., Latorre, A., Lima, J., Lobo, J., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J., Lopez-Reyes, R., Lopez-Saez, J., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P., Martin del Pozo, M., Martin-Martos, F., Mella, C., Mercado, M., Moises, J., Munoz-Blanco, A., Nieto, J., Nofuentes-Perez, E., Nunez-Fernandez, M., Olid-Velilla, M., Olivares, M., Osorio, J., Otalora, S., Otero, R., Paredes, D., Pedrajas, J., Porras, J., Portillo, J., Redondo, I., Rodriguez-Matute, C., Rosa, V., Ruiz-Artacho, P., Ruiz-Ruiz, J., Salgueiro, G., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J., Sancho, T., Soler, S., Suarez-Rodriguez, B., Surinach, J., Torres, M., Torres-Sanchez, A., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valero, B., Valle, R., Varona, J., Vela, L., Vela, J., Vidal, G., Villalobos, A., Villares, P., Zamora, C., Ay, C., Nopp, S., Pabinger, I., Engelen, M., Vanassche, T., Verhamme, P., Maly, R., Accassat, S., Ait Abdallah, N., Bertoletti, L., Bura-Riviere, A., Catella, J., Couturaud, F., Crichi, B., Debourdeau, P., Espitia, O., Farge-Bancel, D., Grange, C., Helfer, H., Lacut, K., Le Mao, R., Mahe, I., Morange, P., Moustafa, F., Poenou, G., Sarlon-Bartoli, G., Suchon, P., Quere, I., Braester, A., Brenner, B., Kenet, G., Tzoran, I., Basaglia, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., De Angelis, A., Di Micco, P., Imbalzano, E., Merla, S., Pesavento, R., Prandoni, P., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Nishimoto, Y., Sato, Y., Make, K., Skride, A., Strautmane, S., Fonseca, S., Martins, F., Meireles, J., Bosevski, M., Bounameaux, H., Mazzolai, L., Caprini, J., and Bui, H.

Subjects
medicine.medical_specialty, VTE risk assessment, Healthy individual, Elevated liver enzymes, Hemorrhage, Gastroenterology, Liver disease, Recurrence, Fibrosis, Internal medicine, Internal Medicine, medicine, Anticoagulation adverse event, Humans, In patient, Registries, Clinical VTE, business.industry, Liver Diseases, Anticoagulants, Venous Thromboembolism, medicine.disease, Im - Original, Non-invasive liver assessment, Healthy individuals, Increased risk, Anticoagulant therapy, Emergency Medicine, Anticoagulation adverse events, business, Venous thromboembolism, Major bleeding
Abstract

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10–2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04–2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02858-x.

Published
2021

25. Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry

Author

Riera-Mestre, A, Mora-Lujan, JM, Trujillo-Santos, J, Del Toro, J, Nieto, JA, Pedrajas, JM, Lopez-Reyes, R, Soler, S, Ballaz, A, Cerda, P, Monreal, M, Prandoni, P, Brenner, B, Farge-Bancel, D, Barba, R, Di Micco, P, Bertoletti, L, Schellong, S, Tzoran, I, Reis, A, Bosevski, M, Bounameaux, H, Maly, R, Verhamme, P, Caprini, JA, Bui, HM, Adarraga, MD, Agud, M, Aibar, MA, Alcalde-Manero, M, Alfonso, J, Amado, C, Arcelus, JI, Barbagelata, C, Barron, M, Barron-Andres, B, Blanco-Molina, A, Camon, AM, Canas, I, Castro, J, de Miguel, J, del Toro, J, Demelo, P, Diaz-Pedroche, C, Diaz-Peromingo, JA, Dominguez, I, Escribano, JC, Falga, C, Fernandez-Capitan, C, Fernandez-Criado, MC, Fidalgo, MA, Flores, K, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Raso, A, Gavin-Bianco, O, Gavin-Sebastian, O, Gil-Diaz, A, Godoy-Diaz, D, Gomez, V, Gomez-Cuelvo, C, Gonzalez-Martinez, J, Grau, E, Guirado, L, Gutierrez, J, Hernandez-Blasco, LM, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Joya, MD, Jou, I, Lalueza, A, Lecumberri, R, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Meseguer, M, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Saez, JB, Lorente, MA, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, Martin-Martos, F, Martinez-Baquerizo, C, Martinez-Garcia, MA, Mellado, M, Moises, J, Morales, MV, Munoz-Bianco, A, Nunez, MJ, Olivares, MC, Olivera, PE, Ortega, C, Osorio, J, Otalora, S, Otero, R, Panadero-Macia, M, Parra, V, Pellejero, G, Perez-Ductor, C, Perez-Rus, G, Penis, ML, Pesantez, D, Porras, JA, Rivas, A, Rodriguez-Cobo, A, Rodriguez-Matute, C, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Ruiz-Sada, P, Sahuquillo, JC, Sala-Sainz, MC, Salgueiro, G, Samperiz, A, Sanchez-Martinez, R, Sanchez-Munoz-Torrero, JF, Segui, E, Suarez, S, Surinach, JM, Tolosa, C, Torres, MI, Uresandi, F, Valero, B, Valle, R, Vidal, G, Aar, C, Villares, P, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Hirmerova, J, Salgado, E, Benzidia, I, Bura-Riviere, A, Debourdeau, P, Courtois, MC, Helfer, H, Hij, A, Mahe, I, Moustafa, F, Braester, A, Bilora, F, Bortoluzzi, C, Ciammaichella, M, Dentali, F, Fermi, P, Imbaizano, E, Lodigiani, C, Maida, R, Mastroiacovo, D, Mumoli, N, Pace, F, Pesavento, R, Pomero, F, Quintavalla, R, Rocci, A, Rota, L, Siniscalchi, C, Tiraferri, E, Tufano, A, Visona, A, Hong, NV, Zalunardo, B, Kalejs, RV, Kigitovica, D, Skride, A, Zdraveska, M, Mazzola, L, Capnini, JA, Tafur, AJ, Vanassche, T, Verhamme, P, Riera-Mestre, A., Mora-Lujan, J. M., Trujillo-Santos, J., Del Toro, J., Nieto, J. A., Pedrajas, J. M., Lopez-Reyes, R., Soler, S., Ballaz, A., Cerda, P., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Verhamme, P., Caprini, J. A., Bui, H. M., Adarraga, M. D., Agud, M., Aibar, M. A., Alcalde-Manero, M., Alfonso, J., Amado, C., Arcelus, J. I., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Camon, A. M., Canas, I., Castro, J., De Miguel, J., Demelo, P., Diaz-Pedroche, C., Diaz-Peromingo, J. A., Dominguez, I. M., Escribano, J. C., Falga, C., Fernandez-Capitan, C., Fernandez-Criado, M. C., Fidalgo, M. A., Flores, K., Font, C., Font, L., Furest, I., Garcia, M. A., Garcia-Bragado, F., Garcia-Raso, A., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Godoy-Diaz, D., Gomez, V., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L. M., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Jou, I., Lalueza, A., Lecumberri, R., Lima, J., Llamas, P., Lobo, J. L., Lopez-Jimenez, L., Lopez-Meseguer, M., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Saez, J. B., Lorente, M. A., Loring, M., Lumbierres, M., Madridano, O., Maestre, A., Marchena, P. J., Martin-Martos, F., Martinez-Baquerizo, C., Martinez-Garcia, M. A., Mellado, M., Moises, J., Morales, M. V., Munoz-Blanco, A., Nunez, M. J., Olivares, M. C., Olivera, P. E., Ortega, C., Osorio, J., Otalora, S., Otero, R., Panadero-Macia, M., Parra, V., Pellejero, G., Perez-Ductor, C., Perez-Rus, G., Peris, M. L., Pesantez, D., Porras, J. A., Rivas, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Sada, P., Sahuquillo, J. C., Sala-Sainz, M. C., Salgueiro, G., Samperiz, A., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J. F., Segui, E., Suarez, S., Surinach, J. M., Tolosa, C., Torres, M. I., Uresandi, F., Valero, B., Valle, R., Vidal, G., Vilar, C., Villares, P., Gutierrez, P., Vazquez, F. J., Vilaseca, A., Vanassche, T., Vandenbriele, C., Hirmerova, J., Salgado, E., Benzidia, I., Bura-Riviere, A., Debourdeau, P., Courtois, M. C., Helfer, H., Hij, A., Mahe, I., Moustafa, F., Braester, A., Bilora, F., Bortoluzzi, C., Ciammaichella, M., Dentali, F., Ferrazzi, P., Imbalzano, E., Lodigiani, C., Maida, R., Mastroiacovo, D., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Rota, L., Siniscalchi, C., Tiraferri, E., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Kalejs, R. V., Kigitovica, D., Skride, A., Zdraveska, M., Mazzolai, L., and Tafur, A. J.

Subjects
0301 basic medicine, Registrie, lcsh:Medicine, 030105 genetics & heredity, Research & Experimental Medicine, THERAPY, 0302 clinical medicine, Pharmacology (medical), Registries, Telangiectasia, EPISTAXIS, Genetics (clinical), Venous Thrombosis, Embòlia pulmonar, Genetics & Heredity, OUTCOMES, FACTOR-VIII, General Medicine, Heparin, Hemorrhagic hereditary telangiectasia, Middle Aged, Pulmonary embolism, Rare diseases, Natural history, Venous thrombosis, Medicine, Research & Experimental, Deep venous thrombosis, Telangiectasia, Hereditary Hemorrhagic, medicine.symptom, Malalties rares, Life Sciences & Biomedicine, medicine.drug, Human, Venous thromboembolism, Adult, medicine.medical_specialty, Hemorrhage, Therapeutics, HHT, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, Risk factor, Deep venous thrombosi, Aged, Tromboflebitis, Bleeding episodes, Science & Technology, business.industry, Research, lcsh:R, Thrombophlebitis, medicine.disease, Terapèutica, equipment and supplies, business, Rare disease, 030217 neurology & neurosurgery, RENDU-OSLER-WEBER
Abstract

BACKGROUND: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). METHODS: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). RESULTS: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. CONCLUSIONS: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis. ispartof: ORPHANET JOURNAL OF RARE DISEASES vol:14 issue:1 ispartof: location:England status: published

Published
2019

26. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE

Author

Weitz, J.I., Haas, S., Ageno, W., Goldhaber, S.Z., Turpie, A.G.G., Goto, S., Angchaisuksiri, P., Nielsen, J.D., Kayani, G., Farjat, A.E., Schellong, S., Bounameaux, H., Mantovani, L.G., Prandoni, P., Kakkar, A.K., Loualidi, A., Colak, A., Bezuidenhout, A., Abdool-Carrim, A., Azeddine, A., Beyers, A., Dees, A., Mohamed, A., Aksoy, A., Abiko, A., Watanabe, A., Krichell, A., Fernandez, A.A., Tosetto, A., Khotuntsov, A., Oropallo, A., Slocombe, A., Kelly, A., Clark, A., Gad, A., Arouni, A., Schmidt, A., Berni, A., Kleiban, A.J., Machowski, A., Kazakov, A., Galvez, A., Lockman, A., Falanga, A., Chauhan, A., Riera-Mestre, A., Mazzone, A., D'Angelo, A., Herdy, A., Kato, A., Salem, A.A.E.E.M., Husin, A., Erdelyi, B., Jacobson, B., Amann-Vesti, B., Battaloglu, B., Wilson, B., Cosmi, B., Francois, B.J., Toufek, B., Hunt, B., Natha, B., Mustafa, B., Kho, B.C.S., Carine, B., Zidel, B., Dominique, B., Christophe, B., Trimarco, B., Luo, C., Cuneo, C.A., Diaz, C.J.S., Schwencke, C., Cader, C., Yavuz, C., Zaidman, C.J., Lunn, C., C. -C., W., Toh, C.H., Chiang, C.-., Elisa, C., Hsia, C.-., Huang, C.-., Kwok, C.-.K., Ward, C., Opitz, C., Jeanneret-Gris, C., C. Y., H., Bidi, C.L., Smith, C., Brauer, C., Lodigiani, C., Francis, C., Wu, C., Staub, D., Theodoro, D., Poli, D., Acevedo, D.-., Adler, D., Jimenez, D., Keeling, D., Scott, D., Imberti, D., Creagh, D., Helene, D.-., Hagemann, D., Le Roux, D., Skowasch, D., Belenky, D., Dorokhov, D., Petrov, D., Zateyshchikov, D., Prisco, D., Moller, D., Kucera, D., Esheiba, E.M., Panchenko, E., Dominique, E., Dogan, E., Kubat, E., Diaz, E.D., Tse, E.W.C., Yeo, E., Hashas, E., Grochenig, E., Tiraferri, E., Blessing, E., Michele, E.O., Usandizaga, E., Porreca, E., Ferroni, F., Nicolas, F., Ayala-Paredes, F., Koura, F., Henry, F., Cosmi, F., Erdkamp, F., Kamalov, G., Dalmau, G.-., Damien, G., Klein, G., Shah, G., Hollanders, G., Merli, G., Plassmann, G., Platt, G., Poirier, G., Sokurenko, G., Haddad, G., Ali, G., Agnelli, G., Gan, G.G., Kaye-Eddie, G., Le Gal, G., Allen, G., Esperon, G.A.L., Jean-Paul, G., Gerofke, H., Elali, H., Burianova, H., Ohler, H.-., Wang, H., Darius, H., Gogia, H.S., Striekwold, H., Gibbs, H., Hasanoglu, H., Turker, H., Franow, H., De Raedt, H., Schroe, H., Eldin, H.S., Zidan, H., Nakamura, H., Kim, H.Y., Lawall, H., Zhu, H., Tian, H., Yhim, H.-., Cate, H., Hwang, H.G., Shim, H., Kim, I., Libov, I., Sonkin, I., Suchkov, I., Song, I.-., Kiris, I., Staroverov, I., Looi, I., De La Azuela Tenorio, I.M., Savas, I., Gordeev, I., Podpera, I., Lee, J.H., Sathar, J., Welker, J., Beyer-Westendorf, J., Kvasnicka, J., Vanwelden, J., Kim, J.Y., Svobodova, J., Gujral, J., Marino, J., Galvar, J.T., Kassis, J., Kuo, J.-., Shih, J.-., Kwon, J.H., Joh, J.H., Park, J.H., Kim, J.S., Yang, J., Krupicka, J., Lastuvka, J., Pumprla, J., Vesely, J., Souto, J.C., Correa, J.A., Duchateau, J., Fletcher, J.P., del Toro, J., Paez, J.G.C., Nielsen, J., Filho, J.D.A., Saraiva, J., Peromingo, J.A.D., Lara, J.G., Fedele, J.L., Surinach, J.M., Chacko, J., Muntaner, J.A., Benitez, J.C.A., Abril, J.M.H., Humphrey, J., Bono, J., Kanda, J., Boondumrongsagoon, J., Yiu, K.H., Chansung, K., Boomars, K., Burbury, K., Kondo, K., Karaarslan, K., Takeuchi, K., Kroeger, K., Zrazhevskiy, K., Svatopluk, K., Shyu, K.-., Vandenbosch, K., Chang, K.-., Chiu, K.-., Jean-Manuel, K., Wern, K.J., Ueng, K.-., Norasetthada, L., Binet, L., Chew, L.P., Zhang, L., Cristina, L.M., Tick, L., Schiavi, L.B., Wong, L.L.L., Borges, L., Botha, L., Capiau, L., Timmermans, L., Lopez, L.E., Ria, L., Blasco, L.M., Guzman, L.A., Cervera, L.F., Isabelle, M., Bosch, M.M., de los Rios Ibarra, M., Fernandez, M.N., Carrier, M., Barrionuevo, M.R., Gamba, M.A.A., Cattaneo, M., Moia, M., Bowers, M., Chetanachan, M., Berli, M.A., Fixley, M., Faghih, M., Stuecker, M., Schul, M., Banyai, M., Koretzky, M., Myriam, M., Gaffney, M.E., Hirano, M., Kanemoto, M., Nakamura, M., Tahar, M., Emmanuel, M., Kovacs, M., Leahy, M., Levy, M., Munch, M., Olsen, M., De Pauw, M., Gustin, M., Van Betsbrugge, M., Boyarkin, M., Homza, M., Koto, M., Abdool-Gaffar, M., Nagib, M.A.F., Dessoki, M.E., Khan, M., Mohamed, M., Kim, M.H., Lee, M.-., Soliman, M., Ahmed, M.S., Bary, M.S.A., Moustafa, M.A., Hameed, M., Kanko, M., Majumder, M., Zubareva, N., Mumoli, N., Abdullah, N.A.N., Makruasi, N., Paruk, N., Kanitsap, N., Duda, N., Nordin, N., Nyvad, O., Barbarash, O., Gurbuz, O., Vilamajo, O.G., Flores, O.N., Gur, O., Oto, O., Marchena, P.J., Carroll, P., Lang, P., Maccallum, P., von Bilderling, P.B., Blombery, P., Verhamme, P., Jansky, P., Bernadette, P., De Vleeschauwer, P., Hainaut, P., Ferrini, P.M., Iamsai, P., Christian, P., Viboonjuntra, P., Rojnuckarin, P., Ho, P., Mutirangura, P., Wells, R., Martinez, R., Miranda, R.T., Kroening, R., Ratsela, R., Reyes, R.L., de Leon, R.F.D., Wong, R.S.M., Alikhan, R., Jerwan-Keim, R., Otero, R., Murena-Schmidt, R., Canevascini, R., Ferkl, R., White, R., Van Herreweghe, R., Santoro, R., Klamroth, R., Mendes, R., Prosecky, R., Cappelli, R., Spacek, R., Singh, R., Griffin, S., S. H., N., Chunilal, S., Middeldorp, S., Nakazawa, S., Toh, S.G., Christophe, S., Isbir, S., Raymundo, S., Ting, S.K., Motte, S., Aktogu, S.O., Donders, S., Cha, S.I., Nam, S.-., Marie-Antoinette, S.-., Maasdorp, S., Sun, S., Wang, S., Essameldin, S.M., Sholkamy, S.M., Kuki, S., Yoshida, S., Matsuoka, S., Mcrae, S., Watt, S., Patanasing, S., Jean-Leopold, S.-., Wongkhantee, S., Bang, S.-., Testa, S., Zemek, S., Behrens, S., Dominique, S., Mellor, S., Singh, S.S.G., Datta, S., Chayangsu, S., Solymoss, S., Everington, T., Abdel-Azim, T.A.A., Suwanban, T., Adademir, T., Hart, T., Beatrice, T., Luvhengo, T., Horacek, T., Zeller, T., Boussy, T., Reynolds, T., Biss, T., Chao, T.-., Casabella, T.S., Onodera, T., Numbenjapon, T., Gerdes, V., Cech, V., Krasavin, V., Tolstikhin, V., Bax, W.A., Malek, W.F.A., W. K., H., Pharr, W., Jiang, W., Lin, W.-., Zhang, W., Tseng, W.-., Lai, W.-., De Backer, W., Haverkamp, W., Yoshida, W., Korte, W., Choi, W., Kim, Y.-., Tanabe, Y., Ohnuma, Y., Mun, Y.-., Balthazar, Y., Park, Y., Shibata, Y., Burov, Y., Subbotin, Y., Coufal, Z., Yang, Z., Jing, Z., Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, Weitz, J, Haas, S, Ageno, W, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Nielsen, J, Kayani, G, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, Kakkar, A, GARFIELD-VTE, I, Falanga, A, MUMC+: HVC Trombosezorg (8), RS: Carim - B04 Clinical thrombosis and Haemostasis, MUMC+: HVC Pieken Trombose (9), MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, and Biochemie

Subjects
Male, Time Factors, Settore MED/09 - Medicina Interna, 030204 cardiovascular system & hematology, PROPHYLAXIS, 0302 clinical medicine, Recurrence, Risk Factors, Cause of Death, Neoplasms, Prospective Studies, Registries, 030212 general & internal medicine, DEEP-VEIN THROMBOSIS, Cancer, Aged, 80 and over, Venous Thrombosis, Hematology, Incidence (epidemiology), Anticoagulant, Hazard ratio, Middle Aged, Treatment Outcome, Female, CLINICAL-PRACTICE GUIDELINES, Cardiology and Cardiovascular Medicine, Venous thromboembolism, Adult, medicine.medical_specialty, Registry, medicine.drug_class, Hemorrhage, Malignancy, Anticoagulation, Risk Assessment, 03 medical and health sciences, Fibrinolytic Agents, SDG 3 - Good Health and Well-being, Internal medicine, medicine, MANAGEMENT, Humans, cardiovascular diseases, Aged, business.industry, Anticoagulants, medicine.disease, Confidence interval, RISK-FACTORS, Observational study, Pulmonary Embolism, business
Abstract

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%), colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.

Published
2020

27. Edoxaban for the treatment of cancer-associated venous thromboembolism

Author

Raskob, GE, van Es, N, Verhamme, P, Carrier, M, Di Nisio, M, Garcia, D, Grosso, MA, Kakkar, AK, Kovacs, MJ, Mercuri, MF, Meyer, G, Segers, A, Shi, M, Wang, TF, Yeo, E, Zhang, G, Zwicker, JI, Weitz, JI, Büller, HR, Beyer-Westendorf, J, Boda, Z, Chlumsky, Y, Gibbs, H, Kamphuizen, PW, Monreal, M, Ockleford, P, Pabinger-Fasching, I, Sinnaeve, P, Beenen, L, Gerdes, V, Laleman, W, Larrey, D, van Mechelen, R, Roos, Y, Scheerder, M, Slagboom, T, Thijs, V, Eikelboom, JW, Crowther, M, Roberts, RS, Vanassche, T, Vandenbriele, C, Debaveye, B, Dani, V, Schwocho, L, Duggal, A, Baker, R, Carroll, P, Chan, N, Coughlin, P, Crispin, P, Gallus, A, Hugman, A, Tran, H, Brodmann, M, Mathies, R, Rossmann, D, Deeren, D, Hainaut, P, Jochmans, K, Vercauter, P, Wautrecht, JC, Champion, P, Gross, P, Lee, A, Shivakumar, S, Tagalakis, V, Zed, E, Kovarova, K, Lastuvka, J, Matoska, P, Prosecky, R, Achkar, A, Aquilanti, S, Chatellain, P, Cony-Makhoul, P, Del Piano, F, Elias, A, Falvo, N, Ferrari, E, Mahé, I, Merle, P, Mismetti, P, Muron, T, Pernod, G, Quere, I, Schmidt, J, Stephan, D, Espinola-Klein, C, Horacek, T, Kröning, R, Oettler, W, Schellong, S, Schön, N, Zwemmrich, C, Farkas, K, Gurzo, M, Nyirati, G, Pecsvarady, Z, Riba, M, Becattini, C, Cattaneo, M, Falanga, A, Ghirarduzzi, A, Imberti, D, Lodigiani, C, Parisi, R, Porreca, E, Squizzato, A, Tassoni, MI, Villalta, S, Visonà, A, Beeker, A, Boersma, W, Brouwer, R, Dees, A, Huisman, M, Kuijer, P, Mairuhu, R, Meijer, K, Middeldorp, S, Otten, HM, van Marwijk-Kooy, M, van Wissen, S, Westerweel, P, Harper, P, Merriman, E, Ockelford, P, Royle, G, Smith, M, Cereto Castro, F, de Oña Navarrete, R, Font Puig, C, Gallardo Díaz, E, Garcia-Bragado Dalmau, F, Ruiz Artacho, P, Santamaria, A, Baumann Kreuziger, L, De Sancho, M, Gaddh, M, Metjian, A, Rojas Hernandez, CM, Shah, V, Smith, W, Wun, T, Xiang, Z, Raskob, G, van Es, N, Verhamme, P, Carrier, M, Di Nisio, M, Garcia, D, Grosso, M, Kakkar, A, Kovacs, M, Mercuri, M, Meyer, G, Segers, A, Shi, M, Wang, T, Yeo, E, Zhang, G, Zwicker, J, Weitz, J, Büller, H, Beyer-Westendorf, J, Boda, Z, Chlumsky, Y, Gibbs, H, Kamphuizen, P, Monreal, M, Ockleford, P, Pabinger-Fasching, I, Sinnaeve, P, Beenen, L, Gerdes, V, Laleman, W, Larrey, D, van Mechelen, R, Roos, Y, Scheerder, M, Slagboom, T, Thijs, V, Eikelboom, J, Crowther, M, Roberts, R, Vanassche, T, Vandenbriele, C, Debaveye, B, Dani, V, Schwocho, L, Duggal, A, Baker, R, Carroll, P, Chan, N, Coughlin, P, Crispin, P, Gallus, A, Hugman, A, Tran, H, Brodmann, M, Mathies, R, Rossmann, D, Deeren, D, Hainaut, P, Jochmans, K, Vercauter, P, Wautrecht, J, Champion, P, Gross, P, Lee, A, Shivakumar, S, Tagalakis, V, Zed, E, Kovarova, K, Lastuvka, J, Matoska, P, Prosecky, R, Achkar, A, Aquilanti, S, Chatellain, P, Cony-Makhoul, P, Del Piano, F, Elias, A, Falvo, N, Ferrari, E, Mahé, I, Merle, P, Mismetti, P, Muron, T, Pernod, G, Quere, I, Schmidt, J, Stephan, D, Espinola-Klein, C, Horacek, T, Kröning, R, Oettler, W, Schellong, S, Schön, N, Zwemmrich, C, Farkas, K, Gurzo, M, Nyirati, G, Pecsvarady, Z, Riba, M, Becattini, C, Cattaneo, M, Falanga, A, Ghirarduzzi, A, Imberti, D, Lodigiani, C, Parisi, R, Porreca, E, Squizzato, A, Tassoni, M, Villalta, S, Visonà, A, Beeker, A, Boersma, W, Brouwer, R, Dees, A, Huisman, M, Kuijer, P, Mairuhu, R, Meijer, K, Middeldorp, S, Otten, H, van Marwijk-Kooy, M, van Wissen, S, Westerweel, P, Harper, P, Merriman, E, Ockelford, P, Royle, G, Smith, M, Cereto Castro, F, de Oña Navarrete, R, Font Puig, C, Gallardo Díaz, E, Garcia-Bragado Dalmau, F, Ruiz Artacho, P, Santamaria, A, Baumann Kreuziger, L, De Sancho, M, Gaddh, M, Metjian, A, Rojas Hernandez, C, Shah, V, Smith, W, Wun, T, Xiang, Z, Graduate School, CCA - Cancer Treatment and Quality of Life, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, Other Research, Other departments, Neurology, APH - Societal Participation & Health, APH - Quality of Care, Coronel Institute of Occupational Health, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
Adult, Dalteparin, Male, Randomization, Pyridines, Hemorrhage, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Recurrence, law, Edoxaban, Neoplasms, medicine, Humans, Aged, Intention-to-treat analysis, Heparin, business.industry, Standard treatment, Low-Molecular-Weight, Anticoagulants, Cancer, Follow-Up Studies, Heparin, Low-Molecular-Weight, Intention to Treat Analysis, Middle Aged, Thiazoles, Venous Thromboembolism, General Medicine, medicine.disease, Thrombosis, chemistry, 030220 oncology & carcinogenesis, Anesthesia, Venous Thromboembolism, cancer, thrombosis, business, medicine.drug
Abstract

BACKGROUND Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. METHODS In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. RESULTS Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P = 0.006 for noninferiority; P = 0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6). CONCLUSIONS Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials. gov number, NCT02073682.)

Published
2018

28. Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

Author

Tzoran I., Brenner B., Sakharov G., Trujillo-Santos J., Lorenzo A., Madridano O., Lopez-Saez J. B., Monreal M., Andujar V., Arcelus J. I., Auguet T., Barba R., Barron M., Barron-Andres B., Bascunana J., Blanco-Molina A., Bueso T., Casado I., Casillas C., Conget F., Del Molino F., Del Toro J., Falga C., Fernandez-Capitan C., Font L., Gallego P., Garcia-Bragado F., Gomez V., Gonzalez J., Gonzalez-Bachs E., Guijarro R., Guil M., Gutierrez J., Hernandez L., Hernandez-Huerta S., Jara-Palomares L., Jaras M. J., Jimenez D., Jimenez R., Lobo J. L., Lopez-Jimenez L., Lopez-Montes L., Lopez-Reyes R., Lorente M. A., Luque J. M., Llutart J., Marchena P. J., Martin M., Martin-Antoran J. M., Mellado M., Nauffal D., Nieto J. A., Ogea J. L., Otero R., Pagan B., Pedrajas J. M., Peris M. L., Porras J. A., Pons I., Riera-Mestre A., Rivas A., Rodriguez-Davila M. A., Roman P., Roncero A., Rosa V., Ruiz-Gimenez N., Ruiz J., Sabio P., Sahuquillo J. C., Samperiz A., Sanchez R., Sanchez Munoz-Torrero J. F., Soler S., Surinach J. M., Tiberio G., Tirado R., Tolosa C., Valero B., Valle R., Vela J., Vidal G., Villalobos A., Vilella V., Malfante P., Villagra M., Vivero F., Verhamme P., Peerlinck K., Maly R., Hirmerova J., Kaletova M., Bertoletti L., Bura-Riviere A., Farge-Bancel D., Grange C., Hij A., Mahe I., Merah A., Quere I., Schellong S., Babalis D., Papadakis M., Tzinieris I., Braester A., Zeltser D., Apollonio A., Barillari G., Ciammaichella M., Di Micco P., Duce R., Guida A., Maida R., Mattei L., Pace F., Piovella C., Pesavento R., Poggio R., Prandoni P., Rota L., Schenone A., Tonello D., Tufano A., Visona A., Zalunardo B., Santos M., Bosevski M., Kovacevic D., Alatri A., Bounameaux H., Calanca L., Mazzolai L., Serrano J. C., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Tzoran, I., Brenner, B., Sakharov, G., Trujillo-Santos, J., Lorenzo, A., Madridano, O., Lopez-Saez, J. B., Monreal, M., Andujar, V., Arcelus, J. I., Auguet, T., Barba, R., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Bueso, T., Casado, I., Casillas, C., Conget, F., Del Molino, F., Del Toro, J., Falga, C., Fernandez-Capitan, C., Font, L., Gallego, P., Garcia-Bragado, F., Gomez, V., Gonzalez, J., Gonzalez-Bachs, E., Guijarro, R., Guil, M., Gutierrez, J., Hernandez, L., Hernandez-Huerta, S., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Jimenez, R., Lobo, J. L., Lopez-Jimenez, L., Lopez-Montes, L., Lopez-Reyes, R., Lorente, M. A., Luque, J. M., Llutart, J., Marchena, P. J., Martin, M., Martin-Antoran, J. M., Mellado, M., Nauffal, D., Nieto, J. A., Ogea, J. L., Otero, R., Pagan, B., Pedrajas, J. M., Peris, M. L., Porras, J. A., Pons, I., Riera-Mestre, A., Rivas, A., Rodriguez-Davila, M. A., Roman, P., Roncero, A., Rosa, V., Ruiz-Gimenez, N., Ruiz, J., Sabio, P., Sahuquillo, J. C., Samperiz, A., Sanchez, R., Sanchez Munoz-Torrero, J. F., Soler, S., Surinach, J. M., Tiberio, G., Tirado, R., Tolosa, C., Valero, B., Valle, R., Vela, J., Vidal, G., Villalobos, A., Vilella, V., Malfante, P., Villagra, M., Vivero, F., Verhamme, P., Peerlinck, K., Maly, R., Hirmerova, J., Kaletova, M., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Grange, C., Hij, A., Mahe, I., Merah, A., Quere, I., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Zeltser, D., Apollonio, A., Barillari, G., Ciammaichella, M., Di Micco, P., Duce, R., Guida, A., Maida, R., Mattei, L., Pace, F., Piovella, C., Pesavento, R., Poggio, R., Prandoni, P., Rota, L., Schenone, A., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Santos, M., Bosevski, M., Kovacevic, D., Alatri, A., Bounameaux, H., Calanca, L., Mazzolai, L., and Serrano, J. C.

Subjects
Male, medicine.medical_specialty, Arterial disease, medicine.drug_class, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Antiplatelet, Humans, In patient, cardiovascular diseases, 030212 general & internal medicine, Aged, business.industry, Anticoagulant, Anticoagulants, Venous Thromboembolism, 3. Good health, Surgery, Treatment Outcome, Increased risk, Anticoagulant therapy, Concomitant, Drug Therapy, Combination, Female, business, Venous thromboembolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Platelet Aggregation Inhibitors, Major bleeding
Abstract

International audience; INTRODUCTION:Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis.METHODS:Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course.RESULTS:1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p

Published
2014
Full Text
View/download PDF

29. Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism

Author

Mellado, M, Trujillo-Santos, J, Bikdeli, B, Jimenez, D, Nunez, MJ, Ellis, M, Marchena, PJ, Vela, JR, Clara, A, Moustafa, F, Monreal, M, Adarraga, MD, Aibar, MA, Alfonso, M, Arcelus, JI, Ballaz, A, Banos, P, Barba, R, Barron, M, Bascunana, J, Blanco-Molina, A, Camon, AM, Carrasco, C, Chasco, L, Cruz, AJ, Del, PR, Del, TJ, Diaz-Pedroche, MC, Diaz-Peromingo, JA, Encabo, M, Falga, C, Fernandez-Aracil, C, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Garcia-Sanchez, I, Gavin, O, Gomez, C, Gomez, V, Gonzalez, J, Grau, E, Guijarro, R, Guirado, L, Gutierrez, J, Hernandez-Blasco, L, Hernando, E, Isern, V, Jara-Palomares, L, Jaras, MJ, Joya, MD, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Martin, M, Martin-Martos, F, Morales, MV, Nieto, JA, Olivares, MC, Otalora, S, Otero, R, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Peris, ML, Pons, I, Porras, JA, Riera-Mestre, A, Rivas, A, Rodriguez-Davila, MA, Rodriguez-Galan, I, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Sahuquillo, JC, Sala-Sainz, MC, Samperiz, A, Sanchez-Artola, B, Sanchez-Martinez, R, Sancho, T, Soler, S, Soto, MJ, Surinach, JM, Tolosa, C, Torres, MI, Uresandi, F, Usandizaga, E, Valero, B, Valle, R, Vela, J, Vidal, G, Villalobos, A, Xifre, B, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Yoo, HHB, Wells, P, Hirmerova, J, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Falvo, N, Farge-Bancel, D, Hij, A, Merah, A, Mahe, I, Quere, I, Braester, A, Brenner, B, Tzoran, I, Antonucci, G, Bilora, F, Bucherini, E, Cattabiani, C, Ciammaichella, M, Dentali, F, Di Micco, P, Doddi, M, Duce, R, Giorgi-Pierfranceschi, M, Grandone, E, Imbalzano, E, Lessiani, G, Maggi, F, Maida, R, Mastroiacovo, D, Pace, F, Pesavento, R, Poggio, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tiraferri, E, Tonello, D, Visona, A, Zalunardo, B, Gibietis, V, Skride, A, Vitola, B, Zdraveska, M, Bounameaux, H, Calanca, L, Fresa, M, and Mazzolai, L

Subjects
Male, medicine.medical_specialty, Vena Cava Filters, Inferior vena cava filter, Hemorrhage, 030204 cardiovascular system & hematology, Lower risk, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Thromboembolism, Anticoagulants, Bleeding, Mortality, Vena cava filter, Venous thromboembolism, Internal Medicine, medicine, Humans, Registries, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Heparin, Middle Aged, Surgery, Clinical trial, Treatment Outcome, Propensity score matching, Emergency Medicine, Female, business, Major bleeding, medicine.drug
Abstract

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95 +/- 52 IU/kg/day vs. 104 +/- 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates. Clinical Trial Registration NCT02832245.

Published
2019

30. Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants

Author

Moustafa, F., Pesavento, R., di Micco, P., Gonzalez-Martinez, J., Quintavalla, R., Peris, M. -L., Porras, J. A., Falvo, N., Banos, P., Monreal, M., Adarraga, M. D., Aibar, M. A., Alfonso, M., Arcelus, J. I., Ballaz, A., Barba, R., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Camon, A. M., Chasco, L., del Pozo, R., de Miguel, J., del Toro, J., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Falga, C., Fernandez-Aracil, C., Fernandez-Capitan, C., Fidalgo, M. A., Font, C., Font, L., Gallego, P., Garcia, M. A., Garcia-Bragado, M. F., Garcia-Morillo, M., Garcia-Raso, A., Gavin, O., Gil, F., Gomez, C., Gomez, V., Gonzalez, J., Grau, E., Grimon, A., Guijarro, R., Gutierrez, J., Hernandez-Comes, H., Hernandez-Blasco, G., Hernando, E., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Llamas, P., Lobo, J. L., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Lumbierres, M., Madridano, O., Maestre, A., Marchena, P. J., Martin-Asenjo, M., Martin-Martos, F., Martin-Romero, M., Miralles, M., Morales, M. V., Moya, E. M., Munoz, C., Nieto, J. A., Nieto, S., Nunez, A., Nunez, M. J., Odriozola, M., Otalora, S., Otero, R., Pedrajas, J. M., Pellejero, G., Perez-Ductor, C., Peris, M. L., Pons, I., Ramirez, L., Riera-Mestre, A., Riesco, D., Rivas, A., Rodriguez, M., Rodriguez-Davila, M. A., Rosa, V., Rosillo-Hernandez, E. M., Ruiz-Artacho, P., Sahuquillo, J. C., Sala-Sainz, M. C., Samperiz, A., Sanchez-Martinez, R., Soler, S., Surinach, J. M., Tolosa, C., Torres, M. I., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valero, B., Valle, R., Vela, J., Vela, L., Vidal, G., Villalobos, A., Vanassche, T., Verhamme, P., Yoo, H. H. B., Wells, P., Hirmerova, J., Maly, R., Salgado, E., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Quere, I., Braester, A., Brenner, B., Ellis, M., Tzoran, I., Andriulli, M., Antonucci, G., Barillari, G., Bortoluzzi, C., Brandolin, B., Bucherini, E., Cattabiani, C., Ciammaichella, M., Dentali, F., Di Micco, P., Duce, R., Giorgipierfranceschi, M., Grandone, E., Imbalzano, E., Lessiani, G., Maida, R., Mastroiacovo, D., Pace, F., Pinelli, M., Poggio, R., Prandoni, P., Rocci, A., Siniscalchi, C., Tiraferri, E., Visona, A., Zalunardo, B., Gibietis, V., Skride, A., Vitola, B., Zdraveska, M., Bounameaux, H., and Mazzolai, L.

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Long Term Adverse Effects, Hemorrhage, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Rivaroxaban, law, Recurrence, Internal medicine, medicine, Humans, Pharmacology (medical), In patient, 030212 general & internal medicine, Aged, Randomized Controlled Trials as Topic, Pharmacology, business.industry, Heparin, Patient Selection, Anticoagulant, Hazard ratio, Anticoagulants, Venous Thromboembolism, Heparin, Low-Molecular-Weight, Middle Aged, Confidence interval, Treatment Outcome, Female, business, Venous thromboembolism, medicine.drug, Factor Xa Inhibitors
Abstract

We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy.

Published
2018

31. Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis

Author

Tufano, Antonella, Ageno, Walter, Di Micco, P., Niglio, A., Rosa, V., Ballaz, A., Braester, A., Rubio, C. M., Isern, V., Imbalzano, E., Monreal, M., Adarraga, M. D., Aibar, M. A., Alfonso, M., Aranda, C., Arcelus, J. I., Barba, R., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Braun, B., Camon, A. M., Carrasco, C., Chasco, L., Cruz, A. J., Cuevas, G., de Miguel, J., del Pozo, R., del Toro, J., Díaz-Pedroche, M. C., Díaz-Peromingo, J. A., Falgá, C., Fernández-Aracil, C., Fernández-Capitán, C., Fernández-Muixi, J., Fidalgo, M. A., Font, C., Font, L., Furest, I., García, M. A., García-Bragado, F., García-Morillo, M., García-Raso, A., García-Rodenas, M., Gavín, O., Gómez, C., Gómez, V., González, J., Grau, E., Guijarro, R., Guirado, L., Gutiérrez, J., Hernández-Blasco, L., Hernando, E., Jara-Palomares, L., Jaras, M. J., Jiménez, D., Jiménez, R., Joya, M. D., Lima, J., Llamas, P., Lobo, J. L., López-Jiménez, L., López-Miguel, P., López-Reyes, R., López-Sáez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Lumbierres, M., Madridano, O., Maestre, A., Marchena, P. J., Martín, M., Martín-Martos, F., Morales, M. V., Nieto, J. A., Núñez, M. J., Olivares, M. C., Otalora, S., Otero, R., Pedrajas, J. M., Pellejero, G., Pérez-Ductor, C., Peris, M. L., Pons, I., Porras, J. A., Riera-Mestre, A., Rivas, A., Rodríguez-Dávila, M. A., Ruiz-Artacho, P., Sahuquillo, J. C., Sala-Sainz, M. C., Sampériz, A., Sánchez-Martínez, R., Sancho, T., Soler, S., Soto, M. J., Suriñach, J. M., Tolosa, C., Torres, M. I., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J., Villalobos, A., Vázquez, F. J., Vilaseca, A., Vanassche, T., Vandenbriele, C., Verhamme, P., Wells, P., Hirmerova, J., Malý, R., Salgado, E., Sánchez, G. T., Benzidia, I., Bertoletti, L., Bura-Riviere, A., Falvo, N., Farge-Bancel, D., Hij, A., Merah, A., Mahé, I., Moustafa, F., Quere, I., Brenner, B., Ellis, M., Tzoran, I., Antonucci, G., Bilora, F., Brandolin, B., Bucherini, E., Cattabiani, C., Ciammaichella, M., Dentali, F., Duce, R., Giorgi-Pierfranceschi, M., Grandone, E., Lessiani, G., Maggi, F., Maida, R., Mastroiacovo, D., Pace, F., Pesavento, R., Pinelli, M., Poggio, R., Prandoni, P., Quintavalla, R., Rocci, A., Siniscalchi, C., Tiraferri, E., Visonà, A., Zalunardo, B., Skride, A., Bosevski, M., Zdraveska, M., Bounameaux, H., Erdmann, A., Fresa, M., Mazzolai, L., and Caprini, J.

Subjects
Male, medicine.medical_specialty, Anticoagulant therapy, Bleeding, Recurrences, Splanchnic vein thrombosis, Anticoagulants, Female, Hemorrhage, Humans, Middle Aged, Recurrence, Splanchnic Circulation, Treatment Outcome, Venous Thrombosis, Hematology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, In patient, Prothrombin time, medicine.diagnostic_test, business.industry, Hazard ratio, Cancer, medicine.disease, Surgery, 030220 oncology & carcinogenesis, business, Venous thromboembolism, Major bleeding
Abstract

Introduction Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. Methods We used the RIETE (Registro Informatizado Enfermedad Trombo Embolica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. Results In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71–5.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47–2.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14–8.17) and anaemia (HR: 4.11; 95%CI: 1.45–11.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68–10.1) were associated with at increased risk for major bleeding. Conclusions The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy.

Published
2017

32. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

Author

Mahe, I., Sterpu, R., Bertoletti, L., Lopez-Jimenez, L., Joan, M. M., Trujillo-Santos, J., Ballaz, A., Hernandez Blasco, L. M., Marchena, P. J., Monreal, M., Ameneiro, E., Arcelus, J. I., Barba, R., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Bueso, T., Casado, I., Conget, F., Del Molino, F., Del Toro, J., Falga, C., Fernandez-Capitan, C., Font, L., Fuentes, M. I., Gallego, P., Garcia-Bragado, F., Garcia-Lorenzo, M. D., Gomez, V., Gonzalez, J., Gonzalez-Bachs, E., Guil, M., Gutierrez, J., Hernandez, L., Hernandez-Huerta, S., Jaras, M. J., Jimenez, D., Lecumberri, R., Lobo, J. L., Lopez-Montes, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Luque, J. M., Madridano, O., Martin, M., Mellado, M., Mora, J. M., Nauffal, D., Nieto, J. A., Nunez, M. J., Ogea, J. L., Paul, H., Pedrajas, J. M., Peris, M. L., Porras, J. A., Riera-Mestre, A., Rivas, A., Rodriguez-Davila, M. A., Roman, P., Rosa, V., Ruiz-Gimenez, N., Ruiz, J., Sahuquillo, J. C., Samperiz, A., Sanchez, R., Sanchez Munoz-Torrero, J. F., Soler, S., Surinach, J. M., Tiberio, G., Tilvan, R. M., Tolosa, C., Uresandi, F., Valdes, M., Valero, B., Valle, R., Vela, J., Vidal, G., Vilella, V., Villalta, J., Verhamme, P., Peerlinck, K., Wells, P., Maly, R., Hirmerova, J., Kaletova, M., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Merah, A., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Zeltser, D., Amitrano, M., Apollonio, A., Barillari, G., Ciammaichella, M., Dalla Valle, F., Di Micco, P., Duce, R., Guida, A., Maida, R., Pasca, S., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Brinquinho, M., Miranda, D., Sousa, M. S., Bosevski, M., Kovacevic, D., Alatri, A., Bounameaux, H., Calanca, L., Mazzolai, L., RIETE Investigators, Ameneiro, E., Arcelus, JI., Ballaz, A., Barba, R., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Bueso, T., Casado, I., Conget, F., del Molino, F., del Toro, J., Falgá, C., Fernández-Capitán, C., Font, L., Fuentes, MI., Gallego, P., García-Bragado, F., García-Lorenzo, MD., Gómez, V., González, J., González-Bachs, E., Guil, M., Gutiérrez, J., Hernández, L., Hernández-Huerta, S., Jaras, MJ., Jiménez, D., Lecumberri, R., Lobo, JL., López-Jiménez, L., López-Montes, L., López-Reyes, R., López-Sáez, JB., Lorente, MA., Lorenzo, A., Luque, JM., Madridano, O., Marchena, PJ., Martín, M., Mellado, M., Monreal, M., Mora, JM., Nauffal, D., Nieto, JA., Núñez, MJ., Ogea, JL., Paul, H., Pedrajas, JM., Peris, ML., Porras, JA., Riera-Mestre, A., Rivas, A., Rodríguez-Dávila, MA., Román, P., Rosa, V., Ruiz-Giménez, N., Ruiz, J., Sahuquillo, JC., Samperiz, A., Sánchez, R., Sánchez Muñoz-Torrero JF., Soler, S., Suriñach, JM., Tiberio, G., Tilván, RM., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valdés, M., Valero, B., Valle, R., Vela, J., Vidal, G., Vilella, V., Villalta, J., Verhamme, P., Peerlinck, K., Wells, P., Malý, R., Hirmerova, J., Kaletova, M., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Zeltser, D., Amitrano, M., Apollonio, A., Barillari, G., Ciammaichella, M., Dalla Valle, F., Di Micco, P., Duce, R., Guida, A., Maida, R., Pasca, S., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visonà, A., Zalunardo, B., Brinquinho, M., Miranda, D., Bosevski, M., Kovacevic, D., Alatri, A., Bounameaux, H., Calanca, L., Sterpu, R., Lopez-Jimenez, L., Joan, M. M., Hernandez Blasco, L. M., Marchena, P. J., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Del Molino, F., Del Toro, J., Falga, C., Fernandez-Capitan, C., Fuentes, M. I., Garcia-Bragado, F., Garcia-Lorenzo, M. D., Gomez, V., Gonzalez, J., Gonzalez-Bachs, E., Gutierrez, J., Hernandez, L., Hernandez-Huerta, S., Jaras, M. J., Jimenez, D., Lobo, J. L., Lopez-Montes, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Luque, J. M., Martin, M., Mora, J. M., Nieto, J. A., Nunez, M. J., Ogea, J. L., Pedrajas, J. M., Peris, M. L., Porras, J. A., Rodriguez-Davila, M. A., Roman, P., Ruiz-Gimenez, N., Sahuquillo, J. C., Sanchez, R., Sanchez Munoz-Torrero, J. F., Surinach, J. M., Tilvan, R. M., Valdes, M., Maly, R., Visona, A., Sousa, M. S., and Mazzolai, L.

Subjects
Male, Time Factors, Vitamin K, lcsh:Medicine, Càncer de ronyó, Deep vein thrombosis, Neoplasms, Antithrombotic, 80 and over, lcsh:Science, Aged, 80 and over, Multidisciplinary, Anticoagulant, Low-Molecular-Weight, Anemia, Venous Thromboembolism, Heparin, Aged, Anticoagulants, Drug Prescriptions, Female, Fibrinolytic Agents, Follow-Up Studies, Guideline Adherence, Heparin, Low-Molecular-Weight, Humans, Middle Aged, 3. Good health, Renal cancer, Cancer treatment, Venous thromboembolism, Research Article, medicine.drug, medicine.medical_specialty, medicine.drug_class, Hemorrhage, Thromboembolism, Internal medicine, medicine, Anticoagulant therapy, Tromboembolisme, Trombosi -- Tractament, business.industry, lcsh:R, Cancer, Odds ratio, medicine.disease, Surgery, Anticoagulants (Medicina), lcsh:Q, Anticoagulants (Medicine), business, Fibrinolytic agent
Abstract

Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26-3.23), age >70 years (OR 1.15, 95% CI 1.06-1.24), immobility (OR 2.06, 95% CI 1.93-2.19), renal insufficiency (OR 2.42, 95% CI 2.15-2.71) and anemia (OR 1.75, 95% CI 1.65-1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64-2.06), immobility (OR 1.51, 95% CI 1.30-1.76) and metastases (OR 3.22, 95% CI 2.87-3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. This Registry is supported by unrestricted educational grants from Sanofi Spain and Bayer Pharma AG. The funding source had no role in the design, protocol development, or conduct of the study; data collection, management, or analysis; interpretation, preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The RIETE Registry was supported with an unrestricted educational grant from Sanofi Spain and Bayer Pharma AG. Bayer Pharma AG’s support was limited to the part of RIETE outside Spain, which accounts for a 20.05% of the total patients included in the RIETE Registry. The authors have nothing to disclose. The authors have declared that no competing interests exist.

Published
2015

33. Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism

Author

Monreal, M, Decousus, H, Prandoni, Paolo, Brenner, B, Barba, R, Di Micco, P, Bertoletti, L, Schellong, S, Papadakis, M, Tzoran, I, Reis, A, Bosevski, M, Bounameaux, H, Malý, R, Adarraga, Md, Arcelus, Ji, Ballaz, A, Barrón, M, Barrón Andrés, B, Bascuñana, J, Blanco Molina, A, Bueso, T, Casado, I, Castejón, N, Conget, F, del Molino, F, del Toro, J, Falgá, C, Fernández Capitán, C, Font, L, Fuentes, Mi, Gallego, P, García Bragado, F, García Lorenzo MD, Gómez, V, González, J, González Bachs, E, Grau, E, Guil, M, Gutiérrez, J, Hernández, L, Hernández Huerta, S, Jaras, Mj, Jiménez, D, Lecumberri, R, Lobo, Jl, López Jiménez, L, López Montes, L, López Reyes, R, López Sáez JB, Lorente, Ma, Lorenzo, A, Luque, Jm, Madridano, O, Marchena, Pj, Martín, M, Nauffal, D, Nieto, Ja, Núñez, Mj, Ogea, Jl, Pedrajas, Jm, Peris, Ml, Porras, Ja, Riera Mestre, A, Rivas, A, Rodríguez Dávila MA, Román, P, Roncero, A, Rosa, V, Ruiz Giménez, N, Ruiz, J, Sahuquillo, Jc, Samperiz, A, Sánchez Muñoz Torrero JF, Soler, S, Suriñach, Jm, Tiberio, G, Tolosa, C, Trujillo Santos, J, Uresandi, F, Valdés, M, Valero, B, Valle, R, Vela, J, Vidal, G, Villalta, J, Verhamme, P, Peerlinck, K, Gadelha, T, Ribeiro, R, Vassalo, J, Wells, P, Hirmerova, J, Kaletova, M, Tomko, T, Bura Riviere, A, Farge Bancel, D, Hij, A, Mahe, I, Merah, A, Babalis, D, Tzinieris, I, Braester, A, Zeltser, D, Amitrano, M, Barillari, G, Ciammaichella, M, Duce, R, Giorgi Pierfranceschi, M, Maida, R, Prandoni, P, Quintavalla, R, Rocci, A, Rota, L, Tiraferri, E, Tonello, D, Tufano, A, Visonà, A, Zalunardo, B, Sá Bastos, M, Sousa, Ms, Rei, R, Kovacevic, D, and Mazzolai, L.

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Hemorrhage, Immobilization, Neoplasms, medicine, Humans, In patient, Registries, Aged, Aged, 80 and over, business.industry, Mortality rate, Anticoagulants, Cancer, Venous Thromboembolism, Hematology, Odds ratio, Middle Aged, medicine.disease, Pulmonary embolism, Surgery, Increased risk, Multivariate Analysis, Female, Pulmonary Embolism, business, Venous thromboembolism
Abstract

Background: The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. Methods: We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. Results: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). Conclusions: One in every three cancer patients dying of PE had recent immobilization for ≥4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis.

Published
2014

34. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

Author

Agnelli, G, Berkowitz, S, Bounameaux, H, Büller, Hr, Cohen, A, Gallus, A, Lensing, Aw, Misselwitz, F, Haskell, L, Prins, Mh, Raskob, G, Schellong, S, Bauersachs, R, van Bellen, B, Boda, Z, Borris, L, Brenner, B, Brighton, T, Chlumsky, J, Davidson, B, Decousus, H, Eriksson, H, Jacobson, B, Kakkar, A, Kwong, Yl, Lee, Lh, Meijer, K, van der Meer, J, Minar, E, Monreal, M, Piovella, F, Sandset, Pm, Smith, M, Tomkowski, W, Verhamme, P, Wang, Y, Wells, P, Brandjes, D, Mac Gillavry, M, Otten, Hm, Carlsson, A, Laporte, S, Schulman, S, Gent, M, Turpie, A, Martinelli, I, Segers, A, Muhlhofer, E, Tewes, M, Trajanovic, M, Muller, K, Kim, C, Gebel, M, Benson, A, Pap, Af, Godrie, J, Horvat Broecker, A, Spadari, G, Peters Wulf, C, Roig, J, Baker, R, Bianchi, A, Blombery, P, Campbell, P, Carroll, P, Geraghty, R, Chong, B, Ramanathan, S, Archis, C, Coughlin, P, Salem, H, Crispin, P, Dean, M, Soni, R, Denaro, C, Kubler, P, Coghlan, D, Gan, Te, Tran, H, Coleman, C, Jackson, D, Khalafallah, A, Leahy, M, Leyden, M, Leyden, D, Sturtz, C, Mccann, A, Gibbs, H, Mcrae, S, Richards, B, Ward, C, Curnow, J, Baghestanian, M, Erdogmus, B, Samaha, E, Nikoupayan Mofrad, M, Hirschl, M, Sturm, W, Kirchmair, R, Marschang, P, Drexel, H, Mathies, R, Pilger, E, Brodmann, M, Weltermann, A, Buche, M, Demelenne, J, Gustin, M, Hainaut, P, Pothen, L, de Leersnyder, J, Motte, S, Schroë, H, Sprynger, M, Peerlinck, K, Delcroix, M, Vermassen, F, Verstraeten, P, Smet, V, Vossaert, R, Panico, M, Costa, C, Blondal, J, Kovacs, M, Rodger, M, Carrier, M, Wong, T, Bi, J, Chen, Z, Chen, R, Jing, Zc, He, J, Liu, C, Liu, S, Long, S, Ma, Y, Shao, Y, Wang, C, Yang, Yh, Xie, C, Xu, J, Ying, K, Zhihong, L, Hola, D, Jirat, S, Vitovec, M, Kovářová, K, Gilík, J, Dosál, J, Mandakova, E, Matoška, P, Podpera, I, Podperova, M, Spacek, R, Urbanova, R, Tuxen, C, Sukles, K, Pietila, K, Vesanen, M, Achkar, A, Agraou, B, Aquilanti, S, Rifaï, A, Berremili, T, Brisot, D, Brousse, C, Tarodo, P, Bura, A, Amid Lacombe, C, Malloizel, J, Boulon, C, Alavoine, L, Crestani, B, Mismetti, P, Buchmuller, A, Accassat, S, Elias, A, Elias, M, Emmerich, J, Ferrari, E, Guérin, T, Beaka, P, Lacroix, P, Szwebel, Ta, Benhamou, Y, de Maistre, E, Falvo, N, Mahe, I, Meneveau, N, Schiele, F, Meyer, G, Sanchez, O, Planquette, B, Mottier, D, Le Moigne, E, Couturaud, F, Parent, F, Pernod, G, Imbert, B, Elkouri, D, Dary, M, Queguiner, A, Quere, I, Galanaud, Jp, Roy, Pm, de Boisjolly Bonnefoi JM, Schmidt, J, Breuil, N, Heuser, S, Sevestre, Ma, Simoneau, G, Bergmann, Jf, Stephan, D, Trinh Duc, A, Gaillardou, A, Grange, C, Fassier, T, Wahl, D, Baron Von Bilderling, P, Kuhlencordt, P, Beyer Westendorf, J, Halbritter, K, Werth, S, Diehm, C, Lawall, H, Eifrig, B, Espinola Klein, C, Weisser, G, Giannitsis, E, Haering, Hu, Hasslacher, C, Herrmann, T, Hoffmann, U, Czihal, M, Horacek, T, Ibe, M, Bauer, A, Kieback, A, Landgraf, H, Lindhoff Last, E, Malyar, N, Petermann, W, Potratz, J, Ranft, J, Röcken, M, Pomper, L, Frommhold, R, Schwaiblmair, M, Berghaus, T, Taute, B, Lau, Yk, Tse, E, Olah, Z, Farkas, K, Kolossváry, E, Gurzó, M, Kis, E, Kovács, A, Landi, A, Lupkovics, G, Pecsvarady, Z, Riba, M, Sipos, G, Parakh, R, Sembiring, R, Barton, J, Goldstein, L, Gavish, D, Hoffman, R, Hussein, O, Inbal, A, Lishner, M, Elis, A, Lugassy, G, Varon, D, Zeltser, D, Rogowski, O, Steinvil, A, Zisman, D, Ageno, W, Ambrosio, G, Cattaneo, M, D'Angelo, A, Ghirarduzzi, A, Lotti, M, Pierfranceschi, Mg, Lodigiani, C, Palareti, G, Barone, M, Beltrametti, C, Porreca, E, Prandoni, Paolo, Spiezia, L, Quintavalla, R, Cho, Wh, Ha, Jw, Kim, Hs, Park, K, Sime, I, Miliauskas, S, Petrauskiene, R, Sathar, J, Beeker, A, Ten Cate, H, De Groot, M, Kamphuisen, P, Douma, R, Kooy, Mv, Coenen, J, Mäkelburg, A, Knol, M, Tichelaar, V, Harper, P, Knottenbelt, E, Ockelford, P, Young, L, Royle, G, Simpson, D, Chunilal, S, Ghanima, W, Foyn, S, Tveit, A, Abola, Mt, Adamiec, R, Gorski, P, Kloczko, J, Lewczuk, J, Nowak, M, Musial, J, Wronski, J, Ng, Hj, Adler, D, Becker, Jh, Ellis, G, Isaacs, R, Bloy, B, Allie, R, Eckstein, F, van Rensburg JH, Schmidt, S, Siebert, H, Zyl, L, Carrera, M, Del Campo, F, Diego, I, Garcia Bragado, F, Jiménez, D, Sánchez Álvarez, J, Redondo, M, Roman Sanchez, P, Villalta, J, Villegas Scivetti, M, Jonson, T, Tygesen, H, Lapidus, L, Ottosson, E, Själander, A, Asmis, L, Banyai, M, Heidemann, M, Baumgartner, I, Righini, M, Frank, U, Hayoz, D, Periard, D, Chang, Wt, Chiu, K, Wang, Ky, Weng, Zc, Angchaisuksiri, P, Pothirat, C, Rojnuckarin, P, Solis, J, Hunt, B, Luckit, J, Albrecht, C, Banish, D, Feinbloom, D, Botnick, W, Chen, D, Dexter, J, Ettinger, N, Gleeson, J, Jaffer, A, Joseph, S, Kennedy, M, Krell, K, Lavender, R, Lyons, R, Moll, S, Nadar, V, Darrow, K, Hardman, V, Rathbun, S, Rehm, J, Rodriguez Cintron, W, Stevens, K, Wright, P, Ramaswamy, M., ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Epidemiologie, MUMC+: KIO Kemta (9), RS: CAPHRI School for Public Health and Primary Care, Department of Vascular Medicine (DVM - AMC), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Epidemiology (MHP), Maastricht University [Maastricht], Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Pulmonary Embolism, Male, Vitamin K, Administration, Oral, Pulmonary Embolism/drug therapy/mortality, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Rivaroxaban, Edoxaban, Recurrence, Hemorrhage/chemically induced, 030212 general & internal medicine, Vitamin K/antagonists & inhibitors, Enoxaparin/adverse effects/therapeutic use, MESH: Treatment Outcome, MESH: Aged, ddc:616, MESH: Middle Aged, Hazard ratio, General Medicine, MESH: Follow-Up Studies, Vitamin K antagonist, MESH: Thiophenes, Middle Aged, Thrombosis, Morpholines/adverse effects/therapeutic use, 3. Good health, Pulmonary embolism, MESH: International Normalized Ratio, Treatment Outcome, Anesthesia, MESH: Administration, Oral, Administration, Combination, Apixaban, Drug Therapy, Combination, Female, MESH: Hemorrhage, medicine.drug, Oral, MESH: Enoxaparin, medicine.drug_class, Morpholines, Anticoagulants/adverse effects/therapeutic use, MESH: Morpholines, Hemorrhage, Thiophenes, MESH: Anticoagulants, 03 medical and health sciences, Drug Therapy, medicine, Humans, International Normalized Ratio, Enoxaparin, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, business.industry, MESH: Vitamin K, Anticoagulants, medicine.disease, MESH: Male, MESH: Recurrence, Regimen, MESH: Drug Therapy, Combination, chemistry, Thiophenes/adverse effects/therapeutic use, business, Pulmonary Embolism, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

Published
2012
Full Text
View/download PDF

35. Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients

Author

Goldhaber, Sz, Leizorovicz, A, Kakkar, A, Haas, Sk, Merli, G, Weitz, Ji, Ceresetto, Jm, Kyrle, P, Gallus, A, Cools, F, Saraiva, J, Faucher, Jp, Chlumsky, J, Husted, S, Emmerich, J, Bauersachs, R, Zeltser, D, Prandoni, Paolo, Ghiraduzzi, A, Leiva, J, Sparby, Ja, Torbiki, A, Kobalava, Z, Jacobson, B, Suarez, C, Fu, M, Savas, I, Parkhomenko, A, Ansell, J, Landis, Jr, Elliott, Cg, Borris, Lc, Samama, Mm, Pinede, L, Becker, F, Coppere, B, Nony, P, Merah, A, Alves, M, Boulet, H, Loppinet, A, Nicol, C, Ohanessian, L, Roncato, C, Knabb, Rm, Liaw, D, Smith, K, Hess, T, Rossi, L, Chen, D, Doan, C, Doran, J, Matheis, E, Ballard, M, Tsarova, O, Levenstein, S, Tvedegaard, M, Akkal, Z, Jure, H, Mercado, Da, Zangroniz, P, Constantino, M, Bello, F, Giumelli, C, de Sagastizabal, D, Risso Patron, F, Ceresetto, J, Dran, R, Vita, N, Baratta, S, Ahuad Guerrero, R, Penchasky, D, Rubinfeld, A, Layden, M, Karrasch, J, Coughlin, P, Peters, M, Gibbs, H, Ward, Ch, Hahn, U, Pilger, E, Minar, E, El Allaf, D, Marechal, P, Motte, S, Verhamme, P, Wollaert, B, Duck, L, Freire, A, Piegas, L, Jorge, Jm, Guimaraes, H, Oliveira, M, Blacher, C, Leães, P, Toniolo, J, Okoshi, M, Rosa, Dd, Cunha, C, Lobo, S, Leader, R, Dhar, A, Tarabain, O, Miron, M, Brossoit, R, Kahn, S, Kassis, J, Douketis, J, Spencer, F, Faucher, J, Alarcon, Ma, Gutierrez Valenzuela, F, Bisbal Malig, C, Vejar, M, Jaramillo, N, Saaibi, D, Londono, D, Kolman, P, Reiterer, P, Ballek, L, Spacek, R, Soucek, M, Patek, F, Vitovec, M, Kovarova, K, Ceska, R, Podpera, I, Faber, J, Oestergaard, L, Vejby Christensen, H, Frost, L, Rasmussen, Sl, Tuxen, C, Ingerslev, J, Knudsen, T, Torp Pedersen, C, Pedersen, C, Nielsen, H, Mottier, D, Simoneau, G, Leduc, J, Lorcerie, B, Paleiron, N, Proust, A, Conri, C, Pernod, G, Mismetti, P, Achkar, A, Maignan, M, Harenberg, J, Beyer, J, Horacek, T, Lawall, H, Hecker, U, Hammerstingl, C, Weil, J, Fischer, D, Brachmann, J, Klepzig, H, Cheng, G, Soltesz, P, Schnabel, R, Futo, L, Jobbagy, L, Singh, P, Talwar, D, Bhadade, R, Bharani, A, Krishnamurthy, S, Goyal, A, Mehta, P, Samiuddin, M, D'Souza, G, Sinha, S, Sathe, P, Sethuraman, S, Jaganmani, S, Sundaram, P, Saxena, A, Mehta, M, Omar, A, Rajkumar, J, Jog, S, Kumar, S, Hayek, T, Hussein, O, Lahav, M, Efrati, S, Elias, M, Grossman, E, Lugassy, G, Porath, A, Porreca, E, Prandoni, P, Tosetto, A, Imberti, D, Pierfranceschi, G, Ghirarduzzi, A, Scannapieco, G, Testa, S, Ling, P, Yusoff, K, Yusof, Z, Lopez Rosas, E, Hernandez, I, Nanez Terreros, H, Flota, L, Campos, E, Alcocer, M, Viergever, P, Sparby, J, Cotrina, R, Salas, M, Pamo, O, Fajardo, L, Horna, M, Ulloa, V, Toce, L, Moncada, Z, Salazar, O, Habaluyas, R, Collado, F, Edmilao, M, Abola, T, Sevilla, R, Torbicki, A, Tracz, W, Kasprzak, J, Jastrzebski, D, Psuja, P, Hiczkiewicz, J, Piepiorka, M, Pulkowski, G, Tyszkiewicz, I, Kuc, K, Gordeev, I, Boyarkin, M, Privalov, D, Abrosimov, V, Reshetko, O, Goloshchekin, B, Vishnevsky, A, Boldueva, S, Kostenko, V, Mkrtchian, V, Chernichka, I, Belenkov, Y, Rodoman, G, Andreev, D, Shvarts, Y, Aleksandrov, O, Zadionchenko, V, Klochkov, O, Tay, J, Jagadesan, R, Basson, M, Siebert, R, Viljoen, J, Gray, T, Abdool Gaffar, M, Suh, G, In, K, Choi, D, Kim, S, Baek, S, Chung, H, Shin, J, Alvarez Sala, L, Cepeda, J, Ferrer, M, Mallibovsky, L, Garcia Morillo, J, Villalta, J, Gomez Cerezo, J, Capitán, F, Gonzalez Garrido, F, Guijarro, C, Jimenez, D, Richart, C, Elf, J, Ueng, K, Huang, T, Karan, A, Erten, N, Abrahamovych, O, Chopey, I, Gavrysiuk, V, Kraiz, I, Karpenko, A, Volkov, V, Denesyuk, V, Kharchenko, N, Tseluyko, V, Batushkin, V, Sushko, V, Yagensky, A, Ignatenko, G, Dziublyk, O, Cohen, A, Bareford, D, Kesteven, P, Mccollum, P, Das, S, Conrad, S, Botnick, W, Nathanson, A, Hamad, A, Fraiz, J, Goytia Leos, D, Fulmer, J, Mclaren, G, Streiff, M, Hahn, B, Ardolic, B, Klausner, H, Welch, M, Pullman, J, Phillips, D, Felt, J, Mitchell, G, Margolis, B, Pendleton, R, Mahesh, A, Barney, J, Shadan, F, Schuller, D, Joslin, S, Feldman, J, Pearl, R, Welker, J, Hazelrigg, M, Stevens, S, Siegel, M, Meade, A, Bates, J, Tahirkheli, N, Rosenberg, D, Dishman, K, Ikerd, T, Feldman, G, O'Connell, C, Vaince, U, Dabbagh, O, Eyster, E, Weinstein, G, Ginsberg, R, Fine, J, Tillinghast, A, Alabi, F, Nathan, R, Haught, H, Oliver, M., Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Thrombosis Research Institute (AKK), University College of London [London] (UCL), Institute for Experimental Oncology and Therapy Research (IEOTR), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Jefferson Medical College (JMC), Thomas Jefferson University Hospitals, Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Pulmonary Embolism, Placebo-controlled study, MESH: Hospitalization, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, MESH: Venous Thromboembolism, chemistry.chemical_compound, 0302 clinical medicine, MESH: Aged, 80 and over, Randomized controlled trial, law, Risk Factors, MESH: Risk Factors, Medicine, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, General Medicine, Orvostudományok, Venous Thromboembolism, Middle Aged, 3. Good health, Pulmonary embolism, Hospitalization, Treatment Outcome, Acute Disease, MESH: Acute Disease, Apixaban, Female, Respiratory Insufficiency, MESH: Hemorrhage, medicine.drug, Adult, medicine.medical_specialty, Randomization, MESH: Enoxaparin, Pyridones, Medicina, Hemorrhage, MESH: Anticoagulants, MESH: Drug Administration Schedule, Klinikai orvostudományok, Drug Administration Schedule, 03 medical and health sciences, Double-Blind Method, Internal medicine, MESH: Pyridones, Humans, Risk factor, Enoxaparin, MESH: Kaplan-Meier Estimate, Aged, Heart Failure, MESH: Humans, business.industry, Anticoagulants, MESH: Adult, medicine.disease, MESH: Male, Surgery, chemistry, Relative risk, Betrixaban, MESH: Heart Failure, Pyrazoles, business, Pulmonary Embolism, MESH: Female, MESH: Pyrazoles, MESH: Respiratory Insufficiency, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome - 2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P = 0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P = 0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin, Supported by Bristol-Myers Squibb and Pfizer

Published
2011
Full Text
View/download PDF

36. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism.

Author

Weitz, J. I., Lensing, A. W. A., Prins, M. H., Bauersachs, R., Beyer-Westendorf, J., Bounameaux, H., Brighton, T. A., Cohen, A. T., Davidson, B. L., Decousus, H., Freitas, M. C. S., Holberg, G., Kakkar, A. K., Haskell, L., van Bellen, B., Pap, A. F., Berkowitz, S. D., Verhamme, P., Wells, P. S., and Prandoni, P.

Subjects
*RIVAROXABAN, *ASPIRIN, *THROMBOEMBOLISM, *ANTICOAGULANTS, *HEMORRHAGE, *COMPARATIVE studies, *DRUG administration, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *STATISTICAL sampling, *VEINS, *EVALUATION research, *RANDOMIZED controlled trials, *BLIND experiment, *PLATELET aggregation inhibitors, *KAPLAN-Meier estimator, THROMBOEMBOLISM prevention, DISEASE relapse prevention
Abstract

Background: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.Methods: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.Results: A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.Conclusions: Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439 .). [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

37. Comparative clinical prognosis of massive and non-massive pulmonary embolism: A registry-based cohort study

Author

Marc Blondon, David Jimenez, Helia Robert‐Ebadi, Jorge Del Toro, Luciano Lopez‐Jimenez, Conxita Falga, Andris Skride, Llorenç Font, Fernando Javier Vazquez, Henri Bounameaux, Manuel Monreal, Paolo Prandoni, Benjamin Brenner, Dominique Farge‐Bancel, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Sebastian Schellong, Inna Tzoran, Abilio Reis, Marijan Bosevski, Radovan Malý, Peter Verhamme, Joseph A Caprini, Hanh My Bui, MD Adarraga, M Agud, J Aibar, MA Aibar, J Alfonso, C Amado, JI Arcelus, C Baeza, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón‐Andrés, A Blanco‐Molina, E Botella, AM Camon, J Castro, MA Caudevilla, P Cerdà, L Chasco, J Criado, C de Ancos, J de Miguel, P Demelo‐Rodríguez, JA Díaz‐Peromingo, J Díez‐Sierra, R Díaz‐Simón, IM Domínguez, M Encabo, JC Escribano, C Falgá, AI Farfán, C Fernández‐Capitán, JL Fernández‐Reyes, MA Fidalgo, K Flores, C Font, I Francisco, C Gabara, F Galeano‐Valle, MA García, F García‐Bragado, MM García‐Mullor, O Gavín‐Blanco, O Gavín‐Sebastián, A Gil‐Díaz, C Gómez‐Cuervo, J González‐Martínez, E Grau, L Guirado, J Gutiérrez, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, MD Joya, I Jou, B Lacruz, R Lecumberri, J Lima, JL Lobo, H López‐Brull, L López‐Jiménez, P López‐Miguel, JJ López‐Núñez, R López‐Reyes, JB López‐Sáez, MA Lorente, A Lorenzo, M Loring, O Madridano, A Maestre, PJ Marchena, M Martín del Pozo, F Martín‐Martos, C Martínez‐Baquerizo, C Mella, M Mellado, MI Mercado, J Moisés, MV Morales, A Muñoz‐Blanco, D Muñoz‐Guglielmetti, N Muñoz‐Rivas, E Nart, JA Nieto, MJ Núñez, MC Olivares, C Ortega‐Michel, MD Ortega‐Recio, J Osorio, S Otalora, R Otero, P Parra, V Parra, JM Pedrajas, G Pellejero, A Pérez‐Jacoiste, ML Peris, D Pesántez, JA Porras, J Portillo, L Reig, A Riera‐Mestre, A Rivas, A Rodríguez‐Cobo, C Rodríguez‐Matute, J Rogado, V Rosa, CM Rubio, P Ruiz‐Artacho, N Ruiz‐Giménez, J Ruiz‐Ruiz, P Ruiz‐Sada, JC Sahuquillo, G Salgueiro, A Sampériz, JF Sánchez‐Muñoz‐Torrero, T Sancho, P Sigüenza, M Sirisi, S Soler, S Suárez, JM Suriñach, G Tiberio, MI Torres, C Tolosa, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, JR Vela, G Vidal, C Vilar, P Villares, C Zamora, P Gutiérrez, FJ Vázquez, T Vanassche, C Vandenbriele, P Verhamme, J Hirmerova, R Malý, E Salgado, I Benzidia, L Bertoletti, A Bura‐Riviere, B Crichi, P Debourdeau, O Espitia, D Farge‐Bancel, H Helfer, I Mahé, F Moustafa, G Poenou, S Schellong, A Braester, B Brenner, I Tzoran, M Amitrano, F Bilora, C Bortoluzzi, B Brandolin, M Ciammaichella, D Colaizzo, F Dentali, P Di Micco, E Giammarino, E Grandone, S Mangiacapra, D Mastroiacovo, R Maida, N Mumoli, F Pace, R Pesavento, F Pomero, P Prandoni, R Quintavalla, A Rocci, C Siniscalchi, A Tufano, A Visonà, N Vo Hong, B Zalunardo, RV Kalejs, K Maķe, M Ferreira, S Fonseca, F Martins, J Meireles, M Bosevski, M Zdraveska, L Mazzolai, JA Caprini, AJ Tafur, I Weinberg, H Wilkins, HM Bui, Blondon, M., Jimenez, D., Robert-Ebadi, H., Del Toro, J., Lopez-Jimenez, L., Falga, C., Skride, A., Font, L., Vazquez, F. J., Bounameaux, H., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Maly, R., Verhamme, P., Caprini, J. A., My Bui, H., Adarraga, M. D., Agud, M., Aibar, J., Aibar, M. A., Alfonso, J., Amado, C., Arcelus, J. I., Baeza, C., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Botella, E., Camon, A. M., Castro, J., Caudevilla, M. A., Cerda, P., Chasco, L., Criado, J., de Ancos, C., de Miguel, J., Demelo-Rodriguez, P., Diaz-Peromingo, J. A., Diez-Sierra, J., Diaz-Simon, R., Dominguez, I. M., Encabo, M., Escribano, J. C., Farfan, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia-Mullor, M. M., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Joya, M. D., Jou, I., Lacruz, B., Lecumberri, R., Lima, J., Lobo, J. L., Lopez-Brull, H., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Baquerizo, C., Mella, C., Mellado, M., Mercado, M. I., Moises, J., Morales, M. V., Munoz-Blanco, A., Munoz-Guglielmetti, D., Munoz-Rivas, N., Nart, E., Nieto, J. A., Nunez, M. J., Olivares, M. C., Ortega-Michel, C., Ortega-Recio, M. D., Osorio, J., Otalora, S., Otero, R., Parra, P., Parra, V., Pedrajas, J. M., Pellejero, G., Perez-Jacoiste, A., Peris, M. L., Pesantez, D., Porras, J. A., Portillo, J., Reig, L., Riera-Mestre, A., Rivas, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rogado, J., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Gimenez, N., Ruiz-Ruiz, J., Ruiz-Sada, P., Sahuquillo, J. C., Salgueiro, G., Samperiz, A., Sanchez-Munoz-Torrero, J. F., Sancho, T., Siguenza, P., Sirisi, M., Soler, S., Suarez, S., Surinach, J. M., Tiberio, G., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J. R., Vidal, G., Vilar, C., Villares, P., Zamora, C., Gutierrez, P., Vanassche, T., Vandenbriele, C., Hirmerova, J., Salgado, E., Benzidia, I., Bura-Riviere, A., Crichi, B., Debourdeau, P., Espitia, O., Helfer, H., Mahe, I., Moustafa, F., Poenou, G., Braester, A., Amitrano, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., Colaizzo, D., Dentali, F., Giammarino, E., Grandone, E., Mangiacapra, S., Mastroiacovo, D., Maida, R., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Kalejs, R. V., Maie, K., Ferreira, M., Fonseca, S., Martins, F., Meireles, J., Zdraveska, M., Mazzolai, L., Tafur, A. J., Weinberg, I., Wilkins, H., and Bui, H. M.

Subjects
Registrie, medicine.medical_specialty, pulmonary embolism, Prognosi, Hemodynamics, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Clinical prognosis, 0302 clinical medicine, Recurrence, Internal medicine, Case fatality rate, medicine, Humans, hemorrhage, mortality, prognosis, thrombolytic therapy, Registries, cardiovascular diseases, business.industry, Anticoagulant, Anticoagulants, Hematology, Venous Thromboembolism, Prognosis, medicine.disease, Confidence interval, Pulmonary embolism, Discontinuation, Cohort Studie, business, Venous thromboembolism, Cohort study, Human
Abstract

Aims Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. Methods and results We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (

Published
2021

38. Current management strategies and long‐term clinical outcomes of upper extremity venous thrombosis

Author

K. Kaasjager, S van Wissen, Giuseppe Camporese, Peter Marschang, Marc Philip Righini, H. M. Otten, Anita Aggarwal, Benilde Cosmi, Suzanne M. Bleker, Jan Beyer-Westendorf, Ettore Porreca, Peter Verhamme, M. Di Nisio, Karina Meijer, A. Kleinjan, T Gary, Teresa Lerede, Angelo Ghirarduzzi, Harry R. Büller, N. van Es, Pieter W. Kamphuisen, Bleker, S.M, van Es, N., Kleinjan, A., Büller, H.R., Kamphuisen, P.W., Aggarwal, A., Beyer-Westendorf, J., Camporese, G., Cosmi, B., Gary, T., Ghirarduzzi, A., Kaasjager, K., Lerede, T., Marschang, P., Meijer, K., Otten, H.-M., Porreca, E., Righini, M., Verhamme, P., van Wissen, S., Di Nisio, M., Other departments, Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiovascular Centre (CVC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
Male, Superficial vein thrombosis, medicine.medical_treatment, neoplasms, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Prevalence, DEEP-VEIN THROMBOSIS, 030212 general & internal medicine, Prospective cohort study, Upper extremity deep vein thrombosi, ddc:616, Venous Thrombosis, upper extremity deep vein thrombosis, Incidence (epidemiology), RIETE REGISTRY, Hazard ratio, Venous Thromboembolism, Hematology, Middle Aged, Pulmonary embolism, Venous thrombosis, Treatment Outcome, WEIGHT HEPARIN DALTEPARIN, Female, hemorrhage, Adult, medicine.medical_specialty, recurrence, PULMONARY-EMBOLISM, POSTTHROMBOTIC SYNDROME, Compression stockings, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, Aged, therapy, business.industry, Anticoagulants, Decision Support Systems, Clinical, medicine.disease, mortality, BLEEDING COMPLICATIONS, Surgery, PROSPECTIVE COHORT, CATHETER-RELATED THROMBOSIS, RISK-FACTORS, Neoplasm, COMPRESSION STOCKINGS, business, Follow-Up Studies
Abstract

Essentials Few data exist on outcome of upper extremity deep and superficial vein thrombosis (UEDVT and UESVT). We followed 102 and 55 patients with UEDVT or UESVT, respectively, for a median of 3.5 years. Risk of recurrent venous thromboembolism was low in both diseases, and the mortality high. Postthrombotic symptoms were infrequent and cancer patients had a higher risk of recurrent VTE. Background There is scant information on the optimal management and clinical outcome of deep and superficial vein thrombosis of the upper extremity (UEDVT and UESVT). Objectives To explore treatment strategies and the incidence of recurrent venous thromboembolism (VTE), mortality, postthrombotic symptoms, and bleeding in patients with UEDVT and UESVT and to assess the prognosis of cancer patients with UEDVT. Patients/methods Follow-up of patients with UEDVT or UESVT, who were enrolled previously in a diagnostic management study. Results We followed 102 and 55 patients with UEDVT and UESVT, respectively, both for a median of 3.5 years. Anticoagulant treatment was started in 100 patients with UEDVT (98%) and in 40 (73%) with UESVT. Nine patients with UEDVT (9%) developed recurrent VTE, 26 (26%) died, 6 (8%) of 72 patients had moderate postthrombotic symptoms, and 5 (5%) experienced major bleeding. One patient with UESVT had a recurrent VTE, 18 (33%) died, none had moderate postthrombotic symptoms, and none had major bleeding. Of the cancer patients with UEDVT, 18% had recurrent VTE vs. 7.5% in non-cancer patients (adjusted hazard ratio 2.2, 95%CI 0.6-8.2). The survival rate was 50% in cancer patients with UEDVT vs. 60% in those without (adjusted HR 0.8, 95%CI 0.4-1.4). Conclusions The risk of recurrent VTE was low in patients with UEDVT, and negligible for UESVT. Mortality was high for both diseases. Postthrombotic symptoms were infrequent and mild. Anticoagulant therapy of UEDVT carried a substantial risk of major bleeding. Cancer patients had a significant risk of recurrent VTE

Published
2016
Full Text
View/download PDF

39. Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Author

Farès Moustafa, Matteo Giorgi Pierfranceschi, Pierpaolo Di Micco, Eugenio Bucherini, Alicia Lorenzo, Aurora Villalobos, José A. Nieto, Beatriz Valero, Ángel L. Sampériz, Manuel Monreal, Hervé Decousus, Paolo Prandoni, Benjamin Brenner, Raquel Barba, Laurent Bertoletti, Inna Tzoran, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Philip Wells, Manolis Papadakis, MD Adarraga, P Agudo, MA Aibar, M Alfonso, JI Arcelus, A Ballaz, R Barba, M Barrón, B Barrón‐Andrés, J Bascuñana, A Blanco‐Molina, I Cañas, I Casado, N Chic, R del Pozo, J del Toro, MC Díaz‐Pedroche, JA Díaz‐Peromingo, C Falgá, C Fernández‐Aracil, C Fernández‐Capitán, MA Fidalgo, C Font, L Font, P Gallego, MA García, F García‐Bragado, O Gavín, C Gómez, V Gómez, J González, E Grau, A Grimón, R Guijarro, L Guirado, J Gutiérrez, G Hernández‐Comes, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, J Jiménez, MD Joya, P Llamas, JL Lobo, P López, L López‐Jiménez, R López‐Reyes, JB López‐Sáez, MA Lorente, M Lumbierres, JM Luque, PJ Marchena, F Martín‐Martos, M Mellado, S Nieto, A Núñez, MJ Núñez, S Otalora, R Otero, JM Pedrajas, G Pérez, C Pérez‐Ductor, ML Peris, I Pons, JA Porras, O Reig, A Riera‐Mestre, D Riesco, A Rivas, M Rodríguez, MA Rodríguez‐Dávila, V Rosa, E Rosillo‐Hernández, P Ruiz‐Artacho, N Ruiz‐Giménez, JC Sahuquillo, MC Sala‐Sainz, R Sánchez‐Martínez, O Sanz, S Soler, B Sopeña, JM Suriñach, C Tolosa, MI Torres, J Troya, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, J Vela, L Vela, MP Vicente, B Xifre, T Vanassche, P Verhamme, HHB Yoo, P Wells, J Hirmerova, R Malý, P Dulíček, E Salgado, L Bertoletti, A Bura‐Riviere, D Farge‐Bancel, A Hij, I Mahé, A Merah, A Braester, B Brenner, I Tzoran, G Antonucci, G Barillari, F Bilora, C Bortoluzzi, B Brandolin, C Cattabiani, M Ciammaichella, N Dell'Elce, F Dentali, R Duce, E Grandone, E Imbalzano, G Lessiani, R Maida, D Mastroiacovo, F Pace, R Parisi, M Pellegrinet, R Pesavento, M Pinelli, R Poggio, P Prandoni, R Quintavalla, A Rocci, E Tiraferri, D Tonello, A Tufano, A Visonà, V Gibietis, A Skride, B Vitola, M Bosevski, M Zdraveska, H Bounameaux, L Mazzolai, RIETE Investigators, Decousus, H., Prandoni, P., Brenner, B., Barba, R., Bertoletti, L., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Malý, R., Wells, P., Papadakis, M., Adarraga, M.D., Agudo, P., Aibar, M.A., Alfonso, M., Arcelus, J.I., Ballaz, A., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Cañas, I., Casado, I., Chic, N., Del Pozo, R., Del Toro, J., Díaz-Pedroche, M.C., Díaz-Peromingo, J.A., Falgá, C., Fernández-Aracil, C., Fernández-Capitán, C., Fidalgo, M.A., Font, C., Font, L., Gallego, P., García, M.A., García-Bragado, F., Gavín, O., Gómez, C., Gómez, V., González, J., Grau, E., Grimón, A., Guijarro, R., Guirado, L., Gutiérrez, J., Hernández-Comes, G., Hernández-Blasco, L., Jara-Palomares, L., Jaras, M.J., Jiménez, D., Jiménez, J., Joya, M.D., Llamas, P., Lobo, J.L., López, P., López-Jiménez, L., López-Reyes, R., López-Sáez, J.B., Lorente, M.A., Lumbierres, M., Luque, J.M., Marchena, P.J., Martín-Martos, F., Mellado, M., Nieto, S., Núñez, A., Núñez, M.J., Otalora, S., Otero, R., Pedrajas, J.M., Pérez, G., Pérez-Ductor, C., Peris, M.L., Pons, I., Porras, J.A., Reig, O., Riera-Mestre, A., Riesco, D., Rivas, A., Rodríguez, M., Rodríguez-Dávila, M.A., Rosa, V., Rosillo-Hernández, E., Ruiz-Artacho, P., Ruiz-Giménez, N., Sahuquillo, J.C., Sala-Sainz, M.C., Sánchez-Martínez, R., Sanz, O., Soler, S., Sopeña, B., Suriñach, J.M., Tolosa, C., Torres, M.I., Troya, J., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J., Vela, L., Vicente, M.P., Xifre, B., Vanassche, T., Verhamme, P., Yoo, H., Hirmerova, J., Dulíček, P., Salgado, E., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahé, I., Merah, A., Braester, A., Antonucci, G., Barillari, G., Bilora, F., Bortoluzzi, C., Brandolin, B., Cattabiani, C., Ciammaichella, M., Dell'Elce, N., Dentali, F., Duce, R., Grandone, E., Imbalzano, E., Lessiani, G., Maida, R., Mastroiacovo, D., Pace, F., Parisi, R., Pellegrinet, M., Pesavento, R., Pinelli, M., Poggio, R., Quintavalla, R., Rocci, A., Tiraferri, E., Tonello, D., Tufano, A., Visonà, A., Gibietis, V., Skride, A., Vitola, B., Zdraveska, M., Mazzolai, L., Moustafa, F., Giorgi Pierfranceschi, M., Di Micco, P., Bucherini, E., Lorenzo, A., Villalobos, A., Nieto, J. A., Valero, B., Samperiz, A. L., Monreal, M., Maly, R., Adarraga, M. D., Aibar, M. A., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Canas, I., del Pozo, R., del Toro, J., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Falga, C., Fernandez-Aracil, C., Fernandez-Capitan, C., Fidalgo, M. A., Garcia, M. A., Garcia-Bragado, F., Gavin, O., Gomez, C., Gomez, V., Gonzalez, J., Grimon, A., Gutierrez, J., Hernandez-Comes, G., Hernandez-Blasco, L., Jaras, M. J., Jimenez, D., Jimenez, J., Joya, M. D., Lobo, J. L., Lopez, P., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Luque, J. M., Marchena, P. J., Martin-Martos, F., Nunez, A., Nunez, M. J., Pedrajas, J. M., Perez, G., Perez-Ductor, C., Peris, M. L., Porras, J. A., Rodriguez, M., Rodriguez-Davila, M. A., Rosillo-Hernandez, E., Ruiz-Gimenez, N., Sahuquillo, J. C., Sala-Sainz, M. C., Sanchez-Martinez, R., Sopena, B., Surinach, J. M., Torres, M. I., Vicente, M. P., Yoo, H. H. B., Dulicek, P., Mahe, I., and Visona, A.

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, anticoagulants, recurrence, venous thromboembolism, hemorrhage, mortality, recurrences, Renal function, 030204 cardiovascular system & hematology, Lower risk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, 030212 general & internal medicine, business.industry, anticoagulant, Retrospective cohort study, Hematology, Odds ratio, medicine.disease, Confidence interval, Surgery, Natural history, Original Article, business, Original Articles: Thrombosis
Abstract

Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. Background Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. Objectives To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE. Methods Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. Results From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile. Conclusions In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

Published
2017

40. Managing reversal of direct oral anticoagulants in emergency situations: Anticoagulation education task force white paper

Author

Ivan S. Milojevic, Gary Randall, Walter Ageno, Francisco Moya, Werner Hacke, H. Bart van der Worp, Jeroen M.L. Hendriks, Peter Verhamme, Harry R. Büller, Konstantinos Tsioufis, José L. Merino, A. John Camm, Trudie Lobban, Anna Falanga, Ageno, W, Büller, H, Falanga, A, Hacke, W, Hendriks, J, Lobban, T, Merino, J, Milojevic, I, Moya, F, van der Worp, H, Randall, G, Tsioufis, K, Verhamme, P, Camm, A, Amsterdam Cardiovascular Sciences, and Vascular Medicine

Subjects
medicine.medical_specialty, Advisory Committees, venous thromboembolism, Administration, Oral, Hemorrhage, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Dabigatran, 03 medical and health sciences, chemistry.chemical_compound, Anticoagulation, 0302 clinical medicine, Rivaroxaban, Edoxaban, Stroke prevention, medicine, reversal agent, Humans, atrial fibrillation, 030212 general & internal medicine, Intensive care medicine, Stroke, reversal agents, stroke prevention, business.industry, Anticoagulants, Atrial fibrillation, Idarucizumab, Hematology, Emergency department, medicine.disease, chemistry, Apixaban, business, medicine.drug, Factor Xa Inhibitors
Abstract

SummaryAnticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24–7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

Published
2016

41. DVT Management and Outcome Trends, 2001 to 2014

Author

Raquel Morillo, David Jiménez, Miguel Ángel Aibar, Daniela Mastroiacovo, Philip S. Wells, Ángel Sampériz, Marta Saraiva de Sousa, Alfonso Muriel, Roger D. Yusen, Manuel Monreal, Hervè Decousus, Paolo Prandoni, Benjamin Brenner, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Sebastian Schellong, Inna Tzoran, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Philip Wells, Manolis Papadakis, P. Agudo, M.A. Aibar, M. Akasbi, M. Alcalde-Manero, V. Andújar, J.I. Arcelus, A. Ballaz, R. Barba, M. Barrón, B. Barrón-Andrés, J. Bascuñana, A. Blanco-Molina, I. Cañas, I. Casado, J. de Miguel, J. del Toro, S. Díaz, J.A. Díaz-Peromingo, C. Falgá, C. Fernández-Capitán, C. Font, L. Font, P. Gallego, F. García-Bragado, M. García-Rodenas, V. Gómez, C.J. González, E. Grau, L. Guirado, J. Gutiérrez, G. Hernández, L. Hernández-Blasco, V. Isern, L. Jara-Palomares, M.J. Jaras, D. Jiménez, J.L. Lobo, L. López-Jiménez, R. López-Reyes, J.B. López-Sáez, M.A. Lorente, A. Lorenzo, O. Madridano, A. Maestre, P.J. Marchena, M. Martín, J.M. Martín-Antorán, F. Martín-Martos, M. Monreal, M.V. Morales, D. Nauffal, J.A. Nieto, S. Nieto, M.J. Núñez, C. Orbegoso, S. Otalora, R. Otero, B. Pagán, J.M. Pedrajas, C. Pérez, G. Pérez, M.L. Peris, I. Pons, J.A. Porras, O. Reig, A. Riera-Mestre, A. Rivas, C. Rodríguez, M.A. Rodríguez-Dávila, V. Rosa, A.S. Rosa-Murillo, N. Ruiz-Giménez, J.C. Sahuquillo, M.C. Sala, A. Sampériz, R. Sánchez, O. Sanz, S. Soler, J.M. Suriñach, C. Tolosa, J. Trujillo-Santos, F. Uresandi, B. Valero, R. Valle, J. Vela, G. Vidal, C. Vilar, J. Villalta, B. Xifre, T. Vanassche, P. Verhamme, P. Wells, J. Hirmerova, R. Malý, T. Tomko, G. Celis, E. Salgado, G.T. Sánchez, L. Bertoletti, A. Bura-Riviere, D. Farge-Bancel, A. Hij, I. Mahé, A. Merah, I. Quere, M. Papadakis, A. Braester, B. Brenner, I. Tzoran, A. Apollonio, G. Barillari, A. Bertone, F. Bilora, E. Bucherini, M. Ciammaichella, P. De Ciantis, F. Dentali, P. Di Micco, R. Duce, P. Ferrazzi, E. Grandone, G. Lessiani, C. Lodigiani, D. Mastroiacovo, F. Pace, R. Pesavento, M. Pinelli, R. Poggio, P. Prandoni, M. Rosa, L. Rota, E. Tiraferri, D. Tonello, A. Tufano, U. Venturelli, A. Visonà, B. Zalunardo, E. Drucka, D. Kigitovica, A. Skride, A. Mafalda, J.L. Ribeiro, M.S. Sousa, M. Bosevski, M. Zdraveska, H. Bounameaux, L. Mazzolai, Morillo, R., Jimenez, D., Aibar, M. A., Mastroiacovo, D., Wells, P. S., Samperiz, A., Saraiva de Sousa, M., Muriel, A., Yusen, R. D., Monreal, M., Decousus, H., Prandoni, P., Brenner, B., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Wells, P., Papadakis, M., Agudo, P., Akasbi, M., Alcalde-Manero, M., Andujar, V., Arcelus, J. I., Ballaz, A., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Canas, I., Casado, I., de Miguel, J., del Toro, J., Diaz, S., Diaz-Peromingo, J. A., Falga, C., Fernandez-Capitan, C., Font, C., Font, L., Gallego, P., Garcia-Bragado, F., Garcia-Rodenas, M., Gomez, V., Gonzalez, C. J., Grau, E., Guirado, L., Gutierrez, J., Hernandez, G., Hernandez-Blasco, L., Isern, V., Jara-Palomares, L., Jaras, M. J., Lobo, J. L., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P. J., Martin, M., Martin-Antoran, J. M., Martin-Martos, F., Morales, M. V., Nauffal, D., Nieto, J. A., Nieto, S., Nunez, M. J., Orbegoso, C., Otalora, S., Otero, R., Pagan, B., Pedrajas, J. M., Perez, C., Perez, G., Peris, M. L., Pons, I., Porras, J. A., Reig, O., Riera-Mestre, A., Rivas, A., Rodriguez, C., Rodriguez-Davila, M. A., Rosa, V., Rosa-Murillo, A. S., Ruiz-Gimenez, N., Sahuquillo, J. C., Sala, M. C., Sanchez, R., Sanz, O., Soler, S., Surinach, J. M., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valero, B., Valle, R., Vela, J., Vidal, G., Vilar, C., Villalta, J., Xifre, B., Vanassche, T., Verhamme, P., Hirmerova, J., Tomko, T., Celis, G., Salgado, E., Sanchez, G. T., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Quere, I., Braester, A., Apollonio, A., Barillari, G., Bertone, A., Bilora, F., Bucherini, E., Ciammaichella, M., De Ciantis, P., Dentali, F., Duce, R., Ferrazzi, P., Grandone, E., Lessiani, G., Lodigiani, C., Pace, F., Pesavento, R., Pinelli, M., Poggio, R., Rosa, M., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Venturelli, U., Visona, A., Zalunardo, B., Drucka, E., Kigitovica, D., Skride, A., Mafalda, A., Ribeiro, J. L., Sousa, M. S., Zdraveska, M., and Mazzolai, L.

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Vena Cava Filters, Hemorrhage, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Rate ratio, survival, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, medicine, Humans, Thrombolytic Therapy, Registries, 030212 general & internal medicine, Mortality, Population Growth, Intensive care medicine, Aged, Retrospective Studies, Aged, 80 and over, Venous Thrombosis, business.industry, Anticoagulants, Disease Management, Heparin, Low-Molecular-Weight, Length of Stay, Middle Aged, Prognosis, medicine.disease, Pulmonary embolism, Emergency medicine, Female, Cardiology and Cardiovascular Medicine, business, Venous thromboembolism, Hospital stay, DVT, prognosi
Abstract

Background A comprehensive evaluation of temporal trends in the treatment of patients who have DVT may assist with identification of modifiable factors that contribute to short-term outcomes. Methods We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies among 26,695 adults with DVT enrolled in the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2014. We also examined temporal trends in risk-adjusted rates of all-cause, pulmonary embolism-related, and bleeding-related death to 30 days after diagnosis. Results The mean length of hospital stay decreased from 9.0 days in 2001 to 2005 to 7.6 days in 2010 to 2014 (P

Published
2016

42. Platelet Count and Major Bleeding in Patients Receiving Vitamin K Antagonists for Acute Venous Thromboembolism, Findings From Real World Clinical Practice

Author

Giorgi-Pierfranceschi, Mateo, Di Micco, Pierpaolo, Cattabiani, Chiara, Guida, Anna, Pagán, Barbara, Morales, María del Valle, Salgado, Estuardo, Suriñach, Jose María, Tolosa, Carles, Monreal, Manuel, RIETE Investigators, RIETE Investigators, Adarraga, M.D., Andújar, V., Arcelus, J.I., Ballaz, A., Barba, R., Barrón, M., Blanco-Molina, A., Casado, I., Castejón-Pina, N., de Miguel, J., del Molino, F., del Toro, J., Diaz, J.A., Falga, C., Font, L., Gallego, P., Garcia- Bragado, F., Gómez, V., González, J., Grau, E., Guijarro, R., Guirado, L., ndez-Blasco, L., Hernández- Huerta, S., Jara-Palomares, L., Jaras, M.J., Jiménez, D., Lacruz, B., Lecumberri, R., Lobo, J.L., López-Reyes, R., Sáez, J.B., Lorente, M.A., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P.J., Martin-Martos, F., Monreal, M., Morales, M.V., Nauffal, D., Nieto, J.A., Odriozola, M., Otero, R., Pagán, B., Pedrajas, J.M., Pérez, G., Peris, M.L., Pons, I., Porras, J.A., Riera-Mestre, A., Rivas, A., Rosa, V., Sabio, P., Sampériz, A., Sánchez, R., Sanz, O., Soler, S., Suriñach, J.M., Tiberio, G., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valero, B., Valle, R., Vela, J., Vela, L., Vidal, G., Vilar, C., Villalobos, A., Villalta, J., Xifre, B., Vanassche, T., Verhamme, P., Wells, P., Hirmerova, J., Maly, R., Salgado, E., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Moustafa, F., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Apollonio, A., Barillari, G., Bucherini, E., Ciammaichella, M., Cola, S., Di Micco, P., Enea, I., Ferrazzi, P., Guida, A., Lessiani, G., Lodigiani, C., Maida, R., Mastroiacovo, D., Pace, F., Pasca, S., Pesavento, R., Pinelli, M., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Belovs, A., Sablinskis, K., Skride, A., Ribeiro, F., Ribeiro, J.L., Bosevski, M., Zdraveska, M., Alatri, A., Bounameaux, H., Calanca, L., and Mazzolai, L.

Subjects
Male, medicine.medical_specialty, Vitamin K, Observational Study, Hemorrhage, Abnormal platelet count, Vitamin k, Gastroenterology, Aged, Anticoagulants, Female, Fibrinolytic Agents, Follow-Up Studies, Humans, International Normalized Ratio, Middle Aged, Registries, Treatment Outcome, Venous Thromboembolism, Platelet Count, Internal medicine, medicine, Platelet, In patient, business.industry, General Medicine, Surgery, Clinical Practice, Anticoagulants/adverse effects, Anticoagulants/therapeutic use, Fibrinolytic Agents/adverse effects, Fibrinolytic Agents/therapeutic use, Hemorrhage/chemically induced, Hemorrhage/epidemiology, Venous Thromboembolism/drug therapy, business, Venous thromboembolism, Major bleeding, Fibrinolytic agent, Research Article
Abstract

The outcome of patients with acute venous thromboembolism (VTE) and abnormal platelet count (PlC) at baseline has not been consistently studied. In real-world clinical practice, a number of patients with abnormal PlC receive vitamin K antagonists (VKAs) to treat acute VTE despite their higher risk of bleeding. We used the Registro Informatizado de Enfermedad TromboEmbólica registry database to compare the rate of major bleeding in patients receiving VKA for long-term therapy of acute VTE according to PlC levels at baseline. Patients were categorized as having very low (450,000/μL) PlC at baseline. Of 55,369 patients recruited as of January 2015, 37,000 (67%) received long-term therapy with VKA. Of these, 611 patients (1.6%) had very low PlC, 4006 (10.8%) had low PlC, 25,598 (69%) had normal PlC, 5801 (15.6%) had high PlC, and 984 (2.6%) had very high PlC at baseline. During the course of VKA therapy (mean, 192 days), there were no differences in the duration or intensity (as measured by international normalized ratio levels) of treatment between subgroups. The rate of major bleeding was 3.6%, 2.1%, 1.9%, 2.1%, and 3.7%, respectively, and the rate of fatal bleeding was 0.98%, 0.17%, 0.29%, 0.34%, and 0.50%, respectively. Patients with very low or very high PlC levels were more likely to have severe comorbidities. We found a nonlinear “U-shaped” relationship between PlC at baseline and major bleeding during therapy with VKA for VTE. Consistent alteration of PlC values at baseline suggested a greater frailty.

Published
2015

43. A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the upper extremity

Author

V. Rosa‐Salazar, J. Trujillo‐Santos, J.A. Díaz Peromingo, A. Apollonio, O. Sanz, R. Malý, F.J. Muñoz‐Rodriguez, J.C. Serrano, S. Soler, M. Monreal, H. Decousus, P. Prandoni, B. Brenner, R. Barba, P. Di Micco, L. Bertoletti, S. Schellong, I. Tzoran, A. Reis, M. Bosevski, H. Bounameaux, P. Wells, M. Papadakis, M.D. Adarraga, A. Alibalic, A. Alvarado‐Faria, J.I. Arcelus, T. Auguet, A. Ballaz, M. Barrón, B. Barrón‐Andrés, J. Bascuñana, J.F. Benítez, A. Blanco‐Molina, T. Bueso, A. Cañas, A. Casado, N. Castejón‐Pina, E.L. Chaves, F del Molino, J del Toro, C. Falgá, C. Fernández‐Capitán, L. Font, P. Gallego, F. García‐Bragado, A. García‐Ortega, V. Gómez, J. González, D. González‐Marcano, E. Grau, R. Guijarro, M. Guil, L. Guirado, J. Gutiérrez‐Guisado, L. Hernández‐Blasco, L. Jara‐Palomares, M.J. Jaras, D. Jiménez, R. Jiménez, B. Lacruz, R. Lecumberri, J.L. Lobo, L. López‐Jiménez, L. López‐Montes, R. López‐Reyes, J.B. López‐Sáez, M.A. Lorente, A. Lorenzo, O. Madridano, A. Maestre, P.J. Marchena, J.M. Martín‐Antorán, F. Martín‐Martos, M.V. Morales, D. Nauffal, J.A. Nieto, M.J. Núñez, S. Otalora, R. Otero, B. Pagán, J.M. Pedrajas, M.L. Peris, I. Pons, J.A. Porras, A. Riera‐Mestre, A. Rivas, M.A. Rodríguez‐Dávila, N. Ruiz‐Giménez, P. Sabio, A. Sampériz, R. Sánchez, M.J. Soto, J.M. Suriñach, G. Tiberio, R. Tirado, C. Tolosa, F. Uresandi, B. Valero, R. Valle, J. Vela, A. Villalobos, J. Villalta, P. Malfante, P. Verhamme, T. Vanassche, T. Tomko, J. Hirmerova, A. Bura‐Riviere, D. Farge‐Bancel, A. Hij, I. Mahe, A. Merah, F. Moustafa, I. Quere, D. Babalis, I. Tzinieris, A. Braester, G. Barillari, E. Bucherini, J. Campodomico, M. Ciammaichella, P. Ferrazzi, R. Maida, F. Pace, S. Pasca, R. Pesavento, C. Piovella, L. Rota, E. Tiraferri, A. Tufano, A. Visonà, A. Skride, A. Belovs, M. Moreira, J.L. Ribeiro, M.S. Sousa, A. Alatri, L. Calanca, L. Mazzolai, Rosa-Salazar, V., Trujillo-Santos, J., Diaz Peromingo, J. A., Apollonio, A., Sanz, O., Maly, R., Munoz-Rodriguez, F. J., Serrano, J. C., Soler, S., Monreal, M., Decousus, H., Prandoni, P., Brenner, B., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Wells, P., Papadakis, M., Adarraga, M. D., Alibalic, A., Alvarado-Faria, A., Arcelus, J. I., Auguet, T., Ballaz, A., Barron, M., Barron-Andres, B., Bascunana, J., Benitez, J. F., Blanco-Molina, A., Bueso, T., Canas, A., Casado, A., Castejon-Pina, N., Chaves, E. L., del Molino, F., del Toro, J., Diaz, J. A., Falga, C., Fernandez-Capitan, C., Font, L., Gallego, P., Garcia-Bragado, F., Garcia-Ortega, A., Gomez, V., Gonzalez, J., Gonzalez-Marcano, D., Grau, E., Guijarro, R., Guil, M., Guirado, L., Gutierrez-Guisado, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Jimenez, R., Lacruz, B., Lecumberri, R., Lobo, J. L., Lopez-Jimenez, L., Lopez-Montes, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P. J., Martin-Antoran, J. M., Martin-Martos, F., Montreal, M., Morales, M. V., Nauffal, D., Nieto, J. A., Nunez, M. J., Otalora, S., Otero, R., Pagan, B., Pedrajas, J. M., Peris, M. L., Pons, I., Porras, J. A., Riera-Mestre, A., Rivas, A., Rodriguez-Davila, M. A., Ruiz-Gimenez, N., Sabio, P., Samperiz, A., Sanchez, R., Soto, M. J., Surinach, J. M., Tiberio, G., Tirado, R., Tolosa, C., Uresandi, F., Valero, B., Valle, R., Vela, J., Villalobos, A., Verhamme, P., Tomko, T., Villalta, J., Malfante, P., Mahe, I., Vanassche, T., Moustafa, F., Babalis, D., Hirmerova, J., Barillari, G., Bucherini, E., Farge-Bance, D., Ciammaichella, M., Ferrazzi, P., Maida, R., Pace, F., Quere, I., Pesavento, R., Piovella, C., Rota, L., Tzinieris, I., Tufano, A., Skride, A., Moreira, M., Ribeiro, J. L., Alatri, A., Calanca, L., Visona, A., Belovs, A., Sousa, M. S., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Adult, Male, Canada, medicine.medical_specialty, Time Factors, Upper extremity, Deep vein, Renal function, Hemorrhage, Risk Assessment, deep vein thrombosis, Decision Support Techniques, Hospital, Predictive Value of Tests, Risk Factors, Deep vein thrombosi, Upper Extremity Deep Vein Thrombosis, Humans, Medicine, Registries, Israel, Adverse effect, Anticoagulant therapy, Aged, Outcome, Deep vein thrombosis, Outpatients, Anticoagulants, Europe, Female, Middle Aged, Pulmonary Embolism, South America, Treatment Outcome, business.industry, Cancer, Outpatient, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Thrombosis, Confidence interval, 3. Good health, Pulmonary embolism, Surgery, outpatients, medicine.anatomical_structure, Heart failure, business
Abstract

International audience; BACKGROUND:No studies have identified which patients with upper-extremity deep vein thrombosis (DVT) are at low risk for adverse events within the first week of therapy.METHODS:We used data from Registro Informatizado de la Enfermedad TromboEmbólica to explore in patients with upper-extremity DVT a prognostic score that correctly identified patients with lower limb DVT at low risk for pulmonary embolism, major bleeding, or death within the first week.RESULTS:As of December 2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515 (45%) were treated at home. During the first week, three patients (0.26%) experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%) died. We assigned 1 point to patients with chronic heart failure, creatinine clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count, recent immobility, or cancer without metastases; 2 points to those with metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL min(-1) . Overall, 759 (67%) patients scored ≤ 1 point and were considered to be at low risk. The rate of the composite outcome within the first week was 0.26% (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95% CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57-0.88). Net reclassification improvement was 22%, and integrated discrimination improvement was 0.0055.CONCLUSIONS:Using six easily available variables, we identified outpatients with upper-extremity DVT at low risk for adverse events within the first week. These data may help to safely treat more patients at home.

Published
2015
Full Text
View/download PDF

44. Outcome of Patients with Venous Thromboembolism and Factor V Leiden or Prothrombin 20210 Carrier Mutations During the Course of Anticoagulation

Author

Inna Tzoran, Manolis Papadakis, Benjamin Brenner, Ángeles Fidalgo, Agustina Rivas, Philip S. Wells, Olga Gavín, María Dolores Adarraga, Farès Moustafa, Manuel Monreal, Hervé Decousus, Paolo Prandoni, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Philip Wells, M.D. Adarraga, M.A. Aibar, M. Alfonso, J.I. Arcelus, R. Barba, M. Barrón, B. Barrón-Andrés, J. Bascuñana, A. Blanco-Molina, T. Bueso, G. Cañada, I. Cañas, N. Chic, R. del Pozo, J. del Toro, M.C. Díaz-Pedroche, J.A. Díaz-Peromingo, C. Falgá, C. Fernández-Capitán, M.A. Fidalgo, C. Font, L. Font, P. Gallego, A. García, M.A. García, F. García-Bragado, P. García-Brotons, O. Gavín, C. Gómez, V. Gómez, J. González, D. González-Marcano, E. Grau, A. Grimón, R. Guijarro, J. Gutiérrez, G. Hernández-Comes, L. Hernández-Blasco, M.J. Hermosa-Los Arcos, L. Jara-Palomares, M.J. Jaras, D. Jiménez, M.D. Joya, P. Llamas, R. Lecumberri, J.L. Lobo, P. López, L. López-Jiménez, R. López-Reyes, J.B. López-Sáez, M.A. Lorente, A. Lorenzo, A. Maestre, P.J. Marchena, F. Martín-Martos, M. Monreal, J.A. Nieto, S. Nieto, A. Núñez, M.J. Núñez, M. Odriozola, R. Otero, J.M. Pedrajas, G. Pérez, C. Pérez-Ductor, M.L. Peris, J.A. Porras, O. Reig, A. Riera-Mestre, D. Riesco, A. Rivas, C. Rodríguez, M.A. Rodríguez-Dávila, V. Rosa, N. Ruiz-Giménez, J.C. Sahuquillo, M.C. Sala-Sainz, A. Sampériz, R. Sánchez-Martínez, R. Sánchez Simón-Talero, O. Sanz, S. Soler, J.M. Suriñach, M.I. Torres, J. Trujillo-Santos, F. Uresandi, B. Valero, R. Valle, J. Vela, M.P. Vicente, A. Villalobos, T. Vanassche, P. Verhamme, P. Wells, J. Hirmerova, R. Malý, T. Tomko, G. del Pozo, E. Salgado, G.T. Sánchez, L. Bertoletti, A. Bura-Riviere, I. Mahé, A. Merah, F. Moustafa, M. Papadakis, A. Braester, B. Brenner, I. Tzoran, G. Antonucci, G. Barillari, F. Bilora, C. Bortoluzzi, C. Cattabiani, M. Ciammaichella, J. Di Biase, P. Di Micco, R. Duce, P. Ferrazzi, M. Giorgi-Pierfranceschi, E. Grandone, E. Imbalzano, C. Lodigiani, R. Maida, D. Mastroiacovo, F. Pace, R. Pesavento, M. Pinelli, R. Poggio, P. Prandoni, L. Rota, E. Tiraferri, D. Tonello, A. Tufano, A. Visonà, B. Zalunardo, V. Gibietis, A. Skride, B. Vitola, P. Monteiro, J.L. Ribeiro, M.S. Sousa, M. Bosevski, M. Zdraveska, H. Bounameaux, L. Calanca, A. Erdmann, L. Mazzolai, Tzoran, I., Papadakis, M., Brenner, B., Fidalgo, A., Rivas, A., Wells, P. S., Gavin, O., Adarraga, M. D., Moustafa, F., Monreal, M., Decousus, H., Prandoni, P., Barba, R., Di Micco, P., Bertoletti, L., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Wells, P., Aibar, M. A., Alfonso, M., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Bueso, T., Canada, G., Canas, I., Chic, N., del Pozo, R., del Toro, J., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Falga, C., Fernandez-Capitan, C., Fidalgo, M. A., Font, C., Font, L., Gallego, P., Garcia, A., Garcia, M. A., Garcia-Bragado, F., Garcia-Brotons, P., Gomez, C., Gomez, V., Gonzalez, J., Gonzalez-Marcano, D., Grau, E., Grimon, A., Guijarro, R., Gutierrez, J., Hernandez-Comes, G., Hernandez-Blasco, L., Hermosa-Los Arcos, M. J., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Llamas, P., Lecumberri, R., Lobo, J. L., Lopez, P., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Maestre, A., Marchena, P. J., Martin-Martos, F., Nieto, J. A., Nieto, S., Nunez, A., Nunez, M. J., Odriozola, M., Otero, R., Pedrajas, J. M., Perez, G., Perez-Ductor, C., Peris, M. L., Porras, J. A., Reig, O., Riera-Mestre, A., Riesco, D., Rodriguez, C., Rodriguez-Davila, M. A., Rosa, V., Ruiz-Gimenez, N., Sahuquillo, J. C., Sala-Sainz, M. C., Samperiz, A., Sanchez-Martinez, R., Sanchez Simon-Talero, R., Sanz, O., Soler, S., Surinach, J. M., Torres, M. I., Trujillo-Santos, J., Uresandi, F., Valero, B., Valle, R., Vela, J., Vicente, M. P., Villalobos, A., Vanassche, T., Verhamme, P., Hirmerova, J., Tomko, T., del Pozo, G., Salgado, E., Sanchez, G. T., Bura-Riviere, A., Mahe, I., Merah, A., Braester, A., Antonucci, G., Barillari, G., Bilora, F., Bortoluzzi, C., Cattabiani, C., Ciammaichella, M., Di Biase, J., Duce, R., Ferrazzi, P., Giorgi-Pierfranceschi, M., Grandone, E., Imbalzano, E., Lodigiani, C., Maida, R., Mastroiacovo, D., Pace, F., Pesavento, R., Pinelli, M., Poggio, R., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Gibietis, V., Skride, A., Vitola, B., Monteiro, P., Ribeiro, J. L., Sousa, M. S., Zdraveska, M., Calanca, L., Erdmann, A., and Mazzolai, L.

Subjects
Male, Heterozygote, medicine.medical_specialty, medicine.drug_class, Low molecular weight heparin, Hemorrhage, 030204 cardiovascular system & hematology, Gene mutation, Thrombophilia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Factor V Leiden, Humans, Anticoagulant therapy, Activated Protein C Resistance, Rivaroxaban, biology, business.industry, Bleeding, Factor V, Anticoagulants, General Medicine, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Mutation, biology.protein, Prothrombin G20210A, Female, Prothrombin, Activated protein C resistance, business, Venous thromboembolism, 030215 immunology, medicine.drug
Abstract

Background Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored. Methods We used the Registro Informatizado de Enfermedad TromboEmbolica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers. Results Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carriers had a similar rate of venous thromboembolism recurrence (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.82-1.64), half the rate of major bleeding (adjusted HR, 0.50; 95% CI, 0.25-0.99) and a nonsignificantly lower rate of nonmajor bleeding (adjusted HR, 0.66; 95% CI, 0.43-1.01) than noncarriers. Prothrombin mutation carriers and noncarriers had a comparable rate of venous thromboembolism recurrence (adjusted HR, 1.00; 95% CI, 0.68-1.48), major bleeding (adjusted HR, 0.75; 95% CI, 0.42-1.34), and nonmajor bleeding events (adjusted HR, 1.10; 95% CI, 0.77-1.57). Conclusions During the anticoagulation course, factor V Leiden carriers had a similar risk for venous thromboembolism recurrence and half the risk for major bleeding compared with noncarriers. This finding may contribute to decision-making regarding anticoagulation duration in selected factor V Leiden carriers with venous thromboembolism.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results