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This consensus document is proposed to clinicians to provide the whole spectrum of deep vein thrombosis management as an update to the 2017 consensus document. New data guiding clinicians in indicating extended anticoagulation, management of patients with cancer, and prevention and management of post-thrombotic syndrome are presented. More data on benefit and safety of non-vitamin K antagonists oral anticoagulants are highlighted, along with the arrival of new antidotes for severe bleeding management.

Objective: To address the association between psychiatric disorders and short-term outcomes after acute symptomatic pulmonary embolism (PE). Methods: We identified adults with PE enrolled in the RIETE registry between December 1, 2013, and January 31, 2019. Using multinomial regression, we assessed the association between a history of psychiatric disorders and the outcomes of all-cause mortality, PE-related mortality, and venous thromboembolism recurrence and bleeding rates through 30 days after initiation of treatment. We also examined the impact of depression on all-cause and PE-specific mortality. Results: Among 13,120 patients diagnosed with acute PE, 16.1% (2115) had psychiatric disorders and 4.2% died within the first 30-days of follow-up. Patients with psychiatric disorders had increased odds for all-cause (adjusted odds ratio [OR] 1.50; 95% CI, 1.21 to 1.86; P < 0.001) and PE-related mortality (adjusted OR 1.64; 95% CI, 1.09 to 2.48; P = 0.02) compared to those without psychiatric disorders. Multinomial logistic regression showed a non-significant trend toward lower risk of recurrences for patients with psychiatric disorders (adjusted OR 0.49; 95% CI, 0.21 to 1.15; P = 0.10). Psychiatric disorders were not significantly associated with increased odds for major bleeds during follow-up (adjusted OR 1.09; 95% CI, 0.85 to 1.40; P = 0.49). Results were consistent in a sensitivity analysis that only considered patients with a diagnosis of depression. Conclusions: In patients with acute PE, history of psychiatric disorders might predict all-cause and PE-related death in the ensuing month after diagnosis.

Background: Acute kidney injury (AKI) is a frequent complication of acute medical and surgical diseases. Recently, we found AKI to occur in one in three patients with pulmonary embolism (PE), being an increased risk of death and bleeding. Evolution of renal function in patients with AKI and PE is unknown. Aim: To report the proportion of patients with AKI who recover a normal renal function, after PE. Methods: In a post-hoc analysis of patients with symptomatic PE, prospectively included from September 2013 to October 2018, in whom AKI (KDIGO guidelines) was diagnosed at the time of PE, and with at least one Serum Creatinine value measurement through the follow-up. The primary outcome was the proportion of patients who recover from AKI, defined as disappearance of AKI criteria during follow-up (any creatinine assessment during the follow-up). Secondary outcomes were timing of recovery, and characteristics associated with AKI recovery during follow-up, in univariable and multivariable analysis. Results: Among the 270 patients with acute PE, 41 (15.19%, 95%CI [11.12-20.03]) had AKI at baseline. Thirty patients (73%, 95%CI [57-86]) recovered, 24 at day 7. Only presence of cancer was associated with no recovery, in univariate analysis. Conclusion: In PE patients with AKI, renal recovery is frequent and rapid. However, about a quarter of patients did not fully recover, at least 90 days after PE.

Introduction: Venous thromboembolism (VTE) represents a relevant cause of morbidity in patients with solid-organ transplantation (SOT), which is recognized as an environmental risk factor for VTE. Nevertheless, there are few data about the management and outcomes in this special population. Methods: The RIETE registry is a worldwide, prospective cohort of consecutive patients presenting with objectively confirmed, acute VTE. We used the data from RIETE registry to describe the clinical and therapeutic characteristics in this population and to assess the outcomes of VTE during SOT. Results: Of 83,210 patients with VTE, SOT was reported in 329 (0.4%) patients. Of these, there were 221 kidney transplant recipients (TR), 41 liver TR, 28 lung TR and 25 heart TR. Patients with SOT were younger, more likely men and to have cardiovascular risk factors or recent surgery, and less likely to have active cancer. VTE in SOT recipients were initially presented with PE less frequently (34% vs 53%). Both anemia and plaquetopenia, and kidney insufficiency (60% vs 35%) were more likely in patients with SOT. Concerning long-term therapy, treatment duration was shorter in the SOT patients (255 vs 289 days), more often with LMWH [OR 1.64 (1.31-2.05)], and less often with DOAC [OR 0.36 (0.19-0-68)]. During the course of anticoagulation, the incidence of bleeding in the SOT recipients was higher, both major [HR 2.55 (1.62-3.84)] and non-major [HR 1.94 (1.23-2.93)]. There were no differences in the rate of recurrent VTE or overall mortality, but bleeding was the explanation of death more frequently in TR [HR 3.28 (1.20-7.33)]. Conclusions: VTE is associated with increased risk of bleeding in SOT recipients.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared.We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PEFrom July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95%Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Background: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. Methods: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001–January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. Results: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6–78.7]); including pregnant patients (58.9% [99% CI, 47.7%–69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9–65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P P Conclusions: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Introduction: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age >= 75 years and/or creatinine clearance [CrCl] levels

To investigate the trend and outcomes of acute pulmonary embolism (PE) during pregnancy and puerperium using a large national database.The National Inpatient Sample was queried to identify pregnancy-related hospitalizations in the United States from January 1, 2007, through September 30, 2015. Temporal trends in the rates of acute PE and in-hospital mortality rates were extracted.Among 37,524,314 hospitalizations, 6,333 patients (0.02%) had acute PE. The prevalence of comorbidities and risk factors such as hypertension, obesity, and smoking increased, but rates of acute PE did not change significantly (18.01 in 2007 vs 19.36 in 2015, per 100,000 hospitalizations, PIn this contemporary analysis of pregnancy-related hospitalizations, acute PE was uncommon, but rates have not decreased over the past decade. Acute PE during pregnancy and puerperium was associated with high maternal mortality, and the rates of in-hospital mortality have not improved. Future studies to improve prevention and management of acute PE during pregnancy and puerperium are warranted.

In patients with cancer-associated venous thromboembolism, knowledge of the estimated rate of recurrent events is important for clinical decision-making regarding anticoagulant therapy. The Ottawa score is a clinical prediction rule designed for this purpose, stratifying patients according to their risk of recurrent venous thromboembolism during the first six months of anticoagulation. We conducted a systematic review and meta-analysis of studies validating either the Ottawa score in its original or modified versions. Two investigators independently reviewed the relevant articles published from 1st June 2012 to 15th December 2018 and indexed in MEDLINE and EMBASE. Nine eligible studies were identified; these included a total of 14,963 patients. The original score classified 49.3% of the patients as high-risk, with a sensitivity of 0.7 [95% confidence interval (CI): 0.6-0.8], a 6-month pooled rate of recurrent venous thromboembolism of 18.6% (95%CI: 13.9-23.9). In the low-risk group, the recurrence rate was 7.4% (95%CI: 3.4-12.5). The modified score classified 19.8% of the patients as low-risk, with a sensitivity of 0.9 (95%CI: 0.4-1.0) and a 6-month pooled rate of recurrent venous thromboembolism of 2.2% (95%CI: 1.6-2.9). In the high-risk group, recurrence rate was 10.2% (95%CI: 6.4-14.6). Limitations of our analysis included type and dosing of anticoagulant therapy. We conclude that new therapeutic strategies are needed in patients at high risk for recurrent cancer-associated venous thromboembolism. Low-risk patients, as per the modified score, could be good candidates for oral anticoagulation. (This systematic review was registered with the International Prospective Registry of Systematic Reviews as: PROSPERO CRD42018099506).

Registro Informatizado de Enfermedad Tromboembólica Investigators., [Objective] Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE., [Methods] We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of, [Results] We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE., [Conclusions] Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Background: The present study aimed to evaluate changes in the incidence, patients' profile and indications of inferior vena cava filters at a single center over the past two decades. Methods: We retrospectively analyzed 187 consecutive patients with a venous thromboembolism requiring a filter at a tertiary hospital between 1999-2018. Within this period the availability of retrievable filters (since 2007) and the withdrawal of filter indication for recurrent venous thromboembolism from guidelines (since 2008) may have contributed to change practice patterns. Patients' profile, filter indication and survival were compared between decades (1999-2008 vs. 2009-2018). Results: The filter insertion rate doubled (60 vs. 127 cases) over 2009-2018. In this later period there was an unexpected rise (15 vs. 68 cases, P

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine–Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3–2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1–1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4–2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1–4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05–2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Made available in DSpace on 2020-12-12T01:52:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-01 Hallux valgus surgery (HVS) is one of the most common orthopedic procedures, often occurring in older adults. Guidelines provide inconsistent recommendations about venous thromboembolism (VTE) prophylaxis after HVS and data are scarce regarding VTE presentation and outcomes in this population. We reported the clinical characteristics and outcomes of VTE following HVS among patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry. We compared the findings with those of other patients in RIETE. Consecutive patients with VTE post HVS were included in the study. Baseline characteristics, administration of VTE prophylaxis prior to diagnosis, presenting symptoms and signs, risk factors for VTE, and 90-day outcomes including recurrent VTE, major bleeding and death were determined. A total of 54 patients with VTE post HVS were identified in RIETE [median age: 64 (interquartile range 56–71) years; 85.2% female] and were compared with 74,111 VTE patients who had not undergone HVS. Among those with VTE post HVS, 63.0% had received VTE prophylaxis, in contrast to 35.6% in the rest of the RIETE cohort. Simplified Pulmonary Embolism Severity Index was zero in 66.7% of the patients with pulmonary embolism post HVS and 33.3% of other RIETE patients (P = 0.011). Compared with other VTE patients, use of estrogens was higher in HVS group (13.0% vs 5.4%, P = 0.01). All patients with VTE post HVS (100%) and most of other VTE patients (99.6%) were treated with anticoagulation, most commonly with low-molecular weight heparins. In contrast to the rest of the patients in RIETE, the absolute number of all fatal and non-fatal outcomes at 90 days was zero in the post HVS group (i.e. no deaths, no recurrence of VTE, and no major bleeding). In a large registry of patients with VTE, all patients with VTE post HVS underwent anticoagulation. These patients had much better outcomes than the rest of VTE patients, with no deaths, recurrences or major bleeding events at 90-day follow-up. Aged & Extended Care Services Central Adelaide Local Health Network The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South Adelaide Geriatrics Training and Research With Aged Care (GTRAC) Centre School of Medicine Faculty of Health and Medical Science University of Adelaide Division of Medical Subspecialties Lyell McEwin Hospital Fireman Vascular Center Massachusetts General Hospital Department of Pneumonology Hospital Universitario Araba Department of Internal Medicine Hospital General Virgen de La Luz Department of Internal Medicine Hospital Reina Sofía Department of Internal Medicine Hospital Comarcal de Axarquía Department of Internal Medicine Hospital Italiano de Buenos Aires Department of Internal Medicine – Pulmonary Division Botucatu Medical School São Paulo State University (UNESP) Division of Cardiology Department of Medicine Columbia University Medical Center/New York-Presbyterian Hospital Yale/YNHH Center for Outcomes Research & Evaluation Cardiovascular Research Foundation (CRF) Hospital Universitari Germans Trias I Pujol Universidad Católica de Murcia Department of Internal Medicine – Pulmonary Division Botucatu Medical School São Paulo State University (UNESP)

Bagkground and aims The influence of proton pump inhibitors (PPIs) on outcome in patients with symptomatic artery disease remains controversial. Methods FRENA is a prospective registry of consecutive outpatients with symptomatic coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD). We compared the risk for subsequent ischemic events or death according to the use of PPIs. Results As of December 2016, 5170 patients were recruited: 1793 (35%) had CAD, 1530 (30%) CVD and 1847 (35%) had PAD. Overall, 2289 patients (44%) were regularly using PPIs. During a median follow-up of 36 months, 172 patients suffered a recurrent myocardial infarction, 139 had ischemic stroke, 71 underwent limb amputation and 267 died (cardiovascular death, 109). On multivariable analysis, patients using PPIs were at a lower risk for subsequent limb amputation (hazard ratio [HR]: 0.53; 95%CI: 0.30–0.94), a similar risk for myocardial infarction (HR: 0.78; 95%CI: 0.55–1.10) or stroke (HR: 0.93; 95%CI: 0.64–1.35) and at a higher risk of death (HR: 1.37; 95%CI: 1.04–1.79). Conclusions Among stable outpatients with symptomatic artery disease, the use of PPIs was associated with a lower risk for subsequent ischemic events but a higher risk for death.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84–91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3–15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6–4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1–13%) among patients in hospital wards and 19% (95% CI: 13–26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

[Background]: Improved prediction of the risk of major bleeding in patients with acute pulmonary embolism (PE) receiving systemic thrombolysis is crucial to guide the choice of therapy. [Methods]: The study included consecutive patients with acute PE who received systemic thrombolysis in the RIETE registry. We used multivariable logistic regression analysis to create a risk score to predict 30-day major bleeding episodes. We externally validated the risk score in patients from the COMMAND VTE registry. In addition, we compared the newly created risk score against the Kuijer and RIETE scores., [Results]: Multivariable logistic regression identified four predictors for major bleeding: recent major bleeding (3 points), age >75 years (1 point), active cancer (1 point) and syncope (1 point) (BACS). Among 1172 patients receiving thrombolytic therapy in RIETE, 446 (38%) were classified as having low risk (none of the variables present, 0 points) of major bleeding according to the BACS score, and the overall 30-day major bleeding rate of this group was 2.9% (95% CI 1.6–4.9%), compared with 44% (95% CI 14–79%) in the high-risk group (>3 points). In the validation cohort, 51% (149 out of 290) of patients were classified as having low risk, and the overall 30-day major bleeding rate of this group was 1.3%. In RIETE, the 30-day major bleeding event rates in the Kuijer and RIETE low-risk strata were 5.3% and 4.4%, respectively., [Conclusions]: The BACS score is an easily applicable aid for prediction of the risk of major bleeding in the population of PE patients who receive systemic thrombolysis.

Background: The optimal management of major bleeding in patients receiving vitamin K antagonists (VKA) for venous thromboembolism (VTE) is unclear.Methods: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the management and 30-day outcomes after major bleeding in patients receiving VKA for VTE.Results: From January 2013 to December 2017, 267 of 18,416 patients (1.4%) receiving long-term VKA for VTE had a major bleeding (in the gastrointestinal tract 78, intracranial 72, hematoma 50, genitourinary 20, other 47). Overall, 151 patients (57%) received blood transfusion; 110 (41%) vitamin K; 37 (14%) fresh frozen plasma; 29 (11%) pro-haemostatic agents and 20 (7.5%) a vena cava filter. During the first 30 days, 59 patients (22%) died (41 died of bleeding) and 13 (4.9%) had a thrombosis. On multivariable analysis, patients with intracranial bleeding (hazard ratio [HR]: 4.58; 95% CI: 2.40-8.72) and those with renal insufficiency at baseline (HR: 2.73; 95% CI: 1.45-5.15) had an increased mortality risk, whereas those receiving vitamin K had a lower risk (HR: 0.47; 0.24-0.92). On the other hand, patients receiving fresh frozen plasma were at increased risk for thrombotic events (HR: 4.22; 95% CI: 1.25-14.3).Conclusions: Major bleeding in VTE patients receiving VKA carries a high mortality rate. Intracranial bleeding and renal insufficiency increased the risk. Fresh frozen plasma seems to increase this risk for recurrent VTE.

International audience; Abstract Venous thromboembolism (VTE) during or after assisted reproductive technologies (ART) is predicted to rise due to the increased number of women undergoing this technique. We present data collected in the RIETE registry up to October 2016. Overall, 41 (0.6%) out of 6,718 women of childbearing age with VTE had an ART-related event. Most of them underwent autologous ART cycles; 23 had isolated deep vein thrombosis (DVT) (56.1%), 12 isolated pulmonary embolism (PE) (29.3%) and 6 simultaneous occurrence of both the events (14.6%). VTE occurred in 20 successful and 21 unsuccessful (i.e. not resulting in a clinical pregnancy) ART cycles. No recurrence was observed at 90 days. Logistic regression showed that isolated PE was significantly more frequent than DVT alone or combined with PE in unsuccessful in vitro fertilization (IVF) (odds ratio [OR]: 4.13, 95% confidence interval [CI]: 1.4\textendash12.4), as well as in contraceptive users (OR: 2.96, 95% CI: 1.95\textendash4.5) and in puerperium (OR: 1.96, 95% CI: 1.16\textendash3.3). After grouping isolated PE and DVT + PE, we found that PE was significantly more frequent in women with unsuccessful IVF and higher body mass index (OR: 5.0, 95% CI: 1.2\textendash20.7 and OR: 1.0, 95%CI: 1.0\textendash1.1, respectively). These data document a higher risk of PE in unsuccessful cycles than in successful ones. The risk is higher than that observed during pregnancy, puerperium and contraception.

Objectives: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. Methods: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL—as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)—was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. Results: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). Conclusions: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.

Background: Epigenetic modifications are key factors modulating the expression of genes involved in the synthesis of phytochemicals. The knowledge of plant epigenetic and genetic variations can contribute to enhance the production of bioactive compounds. These issues have been little explored thus far in Rorippa nasturtium var. aquaticum L. (watercress), an edible and medicinal plant. The aim of the current study was to determine and compare the phenolic composition and epigenetic and genetic variations between wild and cultivated watercress. Results: Significant differences were found in the quantitative phenolic composition between wild and cultivated watercress. The eight primer combinations used in the methylation-sensitive amplification polymorphism (MSAP) method revealed different epigenetic status for each watercress type, the cultivated one being the most epigenetically variable. The genetic variability revealed by the EcoRI/MspI amplification profile and also by eight inter-simple sequence repeat (ISSR) primers was different between the two types of watercress. The results of the Mantel test showed that the correlation between genetic and epigenetic variations has diminished in the cultivated type. Cluster analyses showed that the epigenetic and genetic characterizations clearly discriminated between wild and cultivated watercress. Conclusions: Relevant chemical, epigenetic, and genetic differences have emerged between wild and cultivated watercress. These differences can contribute to fingerprint and develop quality control tools for the integral and safety use and the commercialization of watercress. The richness of epialleles could support the development of tools to manipulate the watercress epigenome to develop high bioproduct–producing cultivars.How to cite: Gutiérrez-Velázquez MV, Almaraz-Abarca N, Herrera-Arrieta Y, et al. Comparison of the phenolic contents and the epigenetic and genetic variability of wild and cultivated watercress (Rorippa nasturtium var. aquaticum L.). Electron J Biotechnol 2018;34. https://doi.org/10.1016/j.ejbt.2018.04.005. Keywords: Bioactive compounds, Bioproducts, Brassicaceae, Cytosine methylation, Edible plants, Epigenetic mechanism, Epigenetic modifications, Epigenome, ISSR, MSAP, Phenolic content

BackgroundThere is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD).Patients and methodsRegistro Informatizado Enfermedad Trombo Embolica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD.ResultsAs of October 2014, 41927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.38.8 months), in remission (9.4 +/- 11.5 months), or without IBD (10.0 +/- 12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95% CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity score matching analysis confirmed the absence of differences in the rate of VTE recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio: 0.84, 95% CI: 0.31-2.23) between patients with or without IBD.ConclusionTherapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.

Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality postoperatively. The use of pharmacologic prophylaxis is effective in reducing the incidence of VTE. However, the prophylaxis is often discontinued at hospital discharge, especially for those with benign disease. The implications of this practice are not known. We assessed the data from a large, ongoing registry regarding the time course of VTE and outcomes after noncancer surgery. Methods We analyzed the RIETE (Computerized Registry on Venous Thromboembolism) registry, which includes data from consecutive patients with symptomatic confirmed VTE. In the present study, we focused on general surgical patients who had developed symptomatic postoperative VTE in the first 8 weeks after noncancer surgery. The main objective was to assess the interval between surgery and the occurrence of VTE. Additional variables included the clinical presentation associated with the event, the use of thrombosis prophylaxis, and unfavorable outcomes. Results The data from 3296 patients were analyzed. The median time from surgery to the detection of VTE was 16 days (interquartile range, 8-30 days). Of the VTE events, 77% were detected after the first postoperative week and 27% after 4 weeks. Overall, 43.9% of the patients with VTE had received pharmacologic prophylaxis after surgery for a median of 8 days (interquartile range, 5-14 days), and three quarters of the VTE events were detected after pharmacologic prophylaxis had been discontinued. Overall, 54% of the patients with VTE had presented with pulmonary embolism. For 15% of the patients, the clinical outcome was unfavorable, including 4% who had died within 90 days. Conclusions The risk of VTE after noncancer general surgery remains high for ≤2 months. More than one half of the patients had presented with symptomatic PE as the VTE event, and 15% had had unfavorable outcomes. Only 44% of these patients had received pharmacologic prophylaxis for around 1 week.

Background Inferior vena cava (IVC) filters are widely used for prevention of pulmonary embolism (PE). However, uncertainty persists about their efficacy and safety. Objectives The authors conducted a systematic review and meta-analysis of the published reports on the efficacy and safety of IVC filters. Methods The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through October 3, 2016, for randomized controlled trials (RCTs) or prospective controlled observational studies of IVC filters versus none in patients at risk of PE. Inverse variance fixed-effects models with odds ratio (OR) as the effect measure were used for primary analyses. Main outcomes included subsequent PE, PE-related mortality, all-cause mortality, and subsequent deep vein thrombosis (DVT). Results The authors' search retrieved 1,986 studies, of which 11 met criteria for inclusion (6 RCTs and 5 prospective observational studies). Quality of evidence for RCTs was low to moderate. Overall, patients receiving IVC filters had lower risk for subsequent PE (OR: 0.50; 95% confidence interval [CI]: 0.33 to 0.75); increased risk for DVT (OR: 1.70; 95% CI: 1.17 to 2.48); nonsignificantly lower PE-related mortality (OR: 0.51; 95% CI: 0.25 to 1.05); and no change in all-cause mortality (OR: 0.91; 95% CI: 0.70 to 1.19). Limiting the results to RCTs showed similar results. Findings were substantively similar across a wide range of sensitivity analyses. Conclusions Very few prospective controlled studies, with limited quality of evidence, exist regarding the efficacy and safety of IVC filters. Overall, filters appear to reduce the risk of subsequent PE, increase the risk for DVT, and have no significant effect on overall mortality.

Introduction The appropriate strategy for initiating oral anticoagulant (OAC) therapy after an acute venous thromboembolism (VTE) depends on the intermediate-term anticoagulant to be used. While heparin bridging to vitamin K antagonists (VKA) is required, the direct oral anticoagulants (DOAC) rivaroxaban (30 mg/day) and apixaban (10 mg/day) can be initiated directly without parenteral anticoagulation. The objective was to evaluate OAC initiation patterns in clinical practice. Materials and methods PREFER in VTE was an international, non-interventional registry conducted between January 2013 and August 2015. Consecutive acute VTE patients were grouped based on their OAC treatment at 1 month after the index event (VKA or DOAC). Results At 1 month, 825 patients were receiving a VKA and 687 a DOAC (rivaroxaban in 685/687 cases). DOAC patients were significantly younger, less comorbid, at a lower bleeding risk, and less frequently diagnosed with pulmonary embolism (34.4% vs. 44.7%). During the first month after VTE, the most common treatment pattern was heparin-OAC overlap for VKA patents (69.6%), and OAC only for DOAC patients (49.1%). However, 28.8% of DOAC patients received a heparin-OAC overlap (median heparin duration: 3 days; IQR: 2–6) and 14.8% were switched from heparin to DOAC. For those on rivaroxaban at 1 month, only 29.7% had received the initial 30 mg/day recommended dose. Clinical event rates were comparable between the DOAC only, heparin-DOAC switch, and heparin-DOAC overlap subgroups at 1 and 6 months. Conclusions Guidelines for DOAC/rivaroxaban initiation after VTE are often not adhered to in clinical practice. This could result in adverse outcomes or suboptimal anticoagulation. Intervention programs to raise awareness amongst physicians may be merited.

Introduction Venous thromboembolism (VTE) represents a serious complication after oncologic surgery. Recent studies have shown that the risk of VTE persists several weeks after surgery. This study assesses the form of presentation and time course of VTE after abdominal and pelvic cancer surgery. Methods Prospective, multicenter, observational study that analyzes data from an international registry (RIETE) that includes consecutive patients with symptomatic VTE. Our study assesses the form and time of presentation of postoperative VTE, as well as main outcomes, in patients operated for abdominopelvic cancer 8 weeks prior to VTE diagnosis. Variables related to the presentation of VTE after hospital discharge are identified. Results Out of the 766 analyzed patients with VTE, 395 (52%) presented pulmonary embolism (PE). Most VTE cases (84%) were detected after the first postoperative week, and 38% after one month. Among patients with VTE in the first postoperative week, 70% presented PE. VTE presented after hospital discharge in 54% of cases. Colorectal, urologic, and gynecologic tumors, the use of radiotherapy, and blood hemoglobin levels were independently associated with VTE diagnosis after hospital discharge. Complications (thrombosis recurrence, bleeding, and death) occurred in 34% of patients with VTE detected before hospital discharge, compared to 24% in VTE after hospital discharge (P Conclusions VTE occurs after hospital discharge in most patients, particularly in those operated for colorectal, urologic, and gynecologic cancer. Pulmonary embolism is more frequent in patients who develop early VTE, who also have worse prognosis.

Resumen Introduccion La enfermedad tromboembolica venosa (ETV) representa una grave complicacion tras la cirugia oncologica. Recientes estudios revelan que el riesgo de ETV postoperatoria se extiende durante varias semanas. Este estudio analiza la forma y momento de presentacion de la ETV tras cirugia oncologica abdominal. Metodos Estudio observacional, prospectivo y multicentrico, que analiza los datos de un registro internacional (RIETE) que incluye pacientes consecutivos con ETV sintomatica. Se evalua la forma y momento de presentacion de la ETV, asi como su pronostico, en pacientes operados por cancer abdominopelvico en las 8 semanas previas a la ETV. Se identifican las variables que se asocian con la presentacion de la ETV tras el alta. Resultados Entre los 766 pacientes analizados, 396 (52%) presentaron embolia pulmonar (EP). La mayoria (84%) de los casos de ETV se presentaron despues de la primera semana de la intervencion y un 38% pasado un mes. El 70% de los pacientes con ETV precoz presentaron EP. El 54% de los casos desarrollaron ETV tras el alta. Los tumores colorrectales y genitourinarios, el uso de radioterapia y los niveles de hemoglobina resultaron variables independientes de ETV tras el alta. El 34% de los pacientes con ETV antes del alta tuvieron complicaciones (recidiva, hemorragia y defuncion), frente al 24% con ETV tras el alta (p Conclusiones La ETV se presenta tras el alta en la mayoria de los pacientes, especialmente en aquellos con cancer colorrectal y genitourinario. La EP es mas frecuente en los pacientes con ETV precoz que, ademas, tienen peor pronostico.

Background Cancer patients are at high risk of venous thromboembolism, particularly during cancer treatment. Conversely to chemotherapy, data on the epidemiology and clinical features of venous thromboembolism during radiation therapy are scarce. There is lack of evidence on the influence of radiation therapy (RT) on outcome in cancer patients with acute venous thromboembolism (VTE). Methods We used the RIETE (Registro Informatizado de Enfermedad ThromboEmbolica) database to assess the clinical characteristics and outcome of prospectively-collected consecutive patients with cancer-associated thrombosis occurred during the course of radiation therapy for cancer. Death, venous thromboembolism recurrences and major bleeding rates during long-term follow-up according to cancer site and treatment were compared Results 9284 Patients with active cancer and VTE were enrolled in RIETE: 4605 with pulmonary embolism (PE) and 4679 with deep vein thrombosis (DVT). In all, 1202 (13%) were receiving RT. This last sub-population had a higher rate of PE recurrences and a similar rate of DVT recurrences or major bleeding than those not receiving RT. Patients on RT had a higher rate of cerebral bleeding. Conclusions In this cohort of cancer patients with VTE, a significant proportion of them received RT before VTE, the latter experienced a higher risk of cerebral bleeding.

Background Whether the localization of nonmassive pulmonary embolism (PE) is associated with the short-term and long-term prognosis of patients remains unknown. Our aim was to characterize associations of nonmassive PE localization with risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation. Methods Among participants of the Registro Informatizado de la Enfermedad ThromboEmbolica (RIETE) registry with incident symptomatic nonmassive PE diagnosed by CT scan, we compared risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation between central PE (main pulmonary artery) and noncentral PE (more peripheral arteries) using Cox proportional hazard-adjusted models. Results Of the 6,674 participants, patients with central PE (40.5%) had age (mean 66 years), sex (46.9% male sex), and proportion of idiopathic (45.0%) and cancer-related (22.3%) PE that were similar to those of patients with noncentral PE. During anticoagulation (5,256.1 patient-years), the risk of recurrent VTE was similar between the two groups (2.5 vs 2.1 per 100 patient-years; adjusted hazard ratio [aHR], 1.32; 95% CI, 0.91-1.90), as were risks of major bleeding and mortality. After anticoagulation was discontinued (2,175.4 patient-years), participants with central PE had a borderline greater risk of recurrent VTE than did participants with noncentral PE (11.0 vs 8.0 per 100 patient-years; aHR, 1.34; 95% CI, 1.01-1.78) but not when restricted to participants after unprovoked PE (13.8 vs 11.9 per 100 patient-years; aHR, 1.15; 95% CI, 0.79-1.68; P = .48). Risks of major bleeding and mortality were similar. Conclusions In nonmassive PE, central localization of PE is associated with greater risk of recurrent VTE after anticoagulation cessation. However, the low magnitude of this association and the absence of association after unprovoked PE suggest that the clinical relevance of this finding is limited and that the duration of anticoagulation should not be tailored to PE localization after nonmassive unprovoked PE.

Introduction Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having “unprovoked” or “provoked” VTE is controversial. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤ 50 years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. Results As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53–3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97–8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50–4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18–1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09–1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07–4.10). Conclusions After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors.

Background We hypothesized that the clinical course of venous thromboembolism in patients with active cancer may differ according to the specificities of primary tumor site. Aim and Methods We used data from RIETE (international registry of patients with venous thromboembolism) to compare the clinical venous thromboembolism-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). Results As of September 2014, 3947 cancer patients were recruited, of whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer. Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively). During the course of anticoagulant therapy (mean duration, 139 days), the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9] events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12 [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate cancer, the rate of venous thromboembolic recurrences was half the rate of major bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient-years), whereas in those with lung cancer, the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95% CI, 8.6-15] per 100 patient-years). Conclusions Significant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research.

Background Women presenting with uterine bleeding during the course of anticoagulant therapy for venous thromboembolism (VTE) present a difficult therapeutic dilemma due to the absence of evidence-based recommendations. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the clinical characteristics of women presenting with uterine bleeding during anticoagulation for VTE, its frequency, time course, management and 30-day outcomes. Results As of October 2016, 31,951 women with VTE were recruited in RIETE. During the course of anticoagulant therapy, 53 (0.17%) developed major uterine bleeding, 118 (0.37%) non-major uterine bleeding and 948 (2.97%) had major bleeding in other sites. Median time elapsed from VTE to bleeding was: 32, 71 and 22 days, respectively. Mean age was: 56±17, 52±20 and 75±14 years, respectively. Women with major uterine bleeding more likely had cancer (51%), anemia (72%), raised platelet count (19%) or recent major bleeding (11%) at VTE presentation than those in the other subgroups. During the first 30 days after bleeding, 17%, 1.7% and 31% of women died, respectively. Of 11 women with uterine bleeding who died, 9 (82%) had cancer, two (18%) died of bleeding and one (9.1%) died of pulmonary embolism after discontinuing anticoagulation. Conclusions Uterine bleeding during the course of anticoagulation for VTE is not uncommon and mostly affects young women. Those with cancer, anaemia, raised platelet count or recent bleeding at baseline are at an increased risk for uterine bleeding during anticoagulation.

Unprovoked venous thromboembolism (VTE) is defi ned as a VTE appearing in the absence of the common risk factors including cancer, surgery, hypomobility, oestrogen use or pregnancy. Around 40% of VTE patients have unprovoked VTE in real life.

Background For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. Methods We performed a meta-analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography-detectable RHT for the primary outcome of short-term all-cause mortality and the secondary outcome of short-term PE-related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms "right heart thrombi," "pulmonary embolism," and "prognos.*" A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Results Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography-detectable RHT died (16.7% [95% CI, 13.8-19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0-4.7]). RHT had a significant association with short-term all-cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE-related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0-11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7-13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies. Conclusions In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. Trial Registry PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/

Resume Introduction Il existe de nombreuses recommandations nationales et internationales sur la maladie thromboembolique veineuse. Sa prise en charge devrait donc etre homogene dans les differents pays d’Europe. Nous avons voulu verifier cette hypothese en France, en Italie et en Espagne. Methode Nous avons utilise les donnees du registre international RIETE pour comparer la prise en charge des patients souffrant d’une maladie thromboembolique veineuse en France, en Italie et en Espagne. Resultats Entre janvier 2001 et janvier 2011, 1548 patients ont ete inclus dans ce registre en France, 2083 en Italie et 29 824 en Espagne. L’heparine de bas poids moleculaire (HBPM) est l’anticoagulant le plus utilise dans les trois pays, mais l’heparine non fractionnee (HNF) est plus utilisee en France et en Italie comparativement a l’Espagne. En France, le nombre de patients recevant des HBPM est inferieur au nombre de patients avec un cancer actif (prevalence du cancer chez les patients inclus en France 22,5 %, frequence d’utilisation des HBPM au long cours 17,4 %). Le filtre cave est utilise plus frequemment en France (5,5 % en France ; 3,2 % en Italie et 2 % en Espagne, p Conclusion Malgre la publication de recommandations internationales, il existe des disparites dans la prise en charge de la maladie thromboembolique veineuse en France, en Italie et en Espagne.

SummaryIn patients with venous thromboembolism (VTE), the influence on outcome of using direct oral anticoagulants (DOACs) at non-recommended doses or regimens (once vs twice daily) has not been investigated yet. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the outcomes in patients with VTE receiving DOACs according to the recommendations of the product label versus in those receiving non-recommended doses and/or regimens. The major outcomes were the rate of VTE recurrences, major bleeding and death during the course of therapy. As of March 2016, 1635 VTE patients had received DOACs for initial therapy and 1725 for long-term therapy. For initial therapy, 287 of 1591 patients (18 %) on rivaroxaban and 22 of 44 (50 %) on apixaban did not receive the recommended therapy. For long-term therapy, 217 of 1611 patients (14 %) on rivaroxaban, 29 of 81 (36 %) on apixaban and 15 of 33 (46 %) on dabigatran did not receive the recommended therapy. During the course of therapy with DOACs, eight patients developed VTE recurrences, 14 had major bleeding and 13 died. Patients receiving DOACs at non-recommended doses and/or regimens experienced a higher rate of VTE recurrences (adjusted HR: 10.5; 95 %CI: 1.28–85.9) and a similar rate of major bleeding (adjusted HR: 1.04; 95 %CI: 0.36–3.03) or death (adjusted HR: 1.41; 95 %CI: 0.46–4.29) than those receiving the recommended doses and regimens. In our cohort, a non-negligible proportion of VTE patients received non-recommended doses and/or regimens of DOACs. This use may be associated with worse outcomes.

SummaryTreatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21%) were categorised at low risk for VTE recurrences, 4,525 (41%) at intermediate risk, and 4,255 (38%) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88% (95% CI 5.31–8.77), 11.8% (95% CI 10.1–13.6), and 21.3% (95% CI 18.8–24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1% (95% CI 18.2–24.3), 79.4% (95% CI: 74.9–84.1), and 134.7% (95% CI: 128.3–141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95% CI: 0.56–0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.

Contexte Il y a un manque de connaissances en ce qui concerne la presentation, la prise en charge et le devenir des patients presentant une maladie thromboembolique veineuse (MTEV). De nombreux sous-groupes cliniquement pertinents (comme les personnes âgees, les hemorragies recentes et les patientes enceintes) ont ete sous-representes dans les essais cliniques. En outre, le design des essais cliniques est interessant dans certains scenarios, comme par exemple ceux presentant une embolie pulmonaire (EP) hemodynamiquement instable. Objectifs Registro Informatizado Enfermedad TromboEmbolica (RIETE) est un grand registre prospectif et international en cours, concu pour repondre a ces besoins non satisfaits en utilisant des donnees representatives de plusieurs centres. Methodes Cree en Espagne en 2001, RIETE comprend actuellement 206 centres repartis dans 28 pays et a recrute plus de 87 000 patients atteints de MTEV. L’objectif principal est d’ameliorer la prise en charge de la MTEV grâce a une meilleure comprehension de la prevention, ainsi que des donnees demographiques, des comorbidites, des schemas de traitement et du devenir des patients atteints de MTEV. Resultats RIETE a contribue a caracteriser le modele de presentation et de devenir de la MTEV, y compris dans les sous-groupes peu etudies mentionnes precedemment, dans plus de 150 articles de recherche. RIETE a recemment etendu ses activites a la collecte de donnees sur le devenir a long terme et a elargi ses criteres d’inclusion pour inclure d’autres formes de thrombose veineuse (telles que la thrombose veineuse cerebrale et la thrombose veineuse splanchnique). La plateforme RIETE est egalement utilisee pour mener des etudes comparatives pragmatiques d’efficacite, notamment des essais randomises. Les prochaines etapes seraient axees sur la collaboration avec d’autres centres dans le monde et sur les efforts visant a assurer la qualite et l’extension du registre. RIETE devrait continuer a fournir des preuves cliniques pour les sous-groupes de MTEV sous-etudies et jouer un role plus important dans la facilitation d’etudes multicentriques (et internationales) pouvant etre utilisees pour evaluer les variations et les disparites des soins, l’amelioration de la qualite et conduire des etudes comparatives d’efficacite. Conclusions RIETE est un vaste registre, en cours, de patients atteints de MTEV et d’autres affections thrombotiques. Ses resultats pourraient etre utiles pour ameliorer notre comprehension de l’epidemiologie, des tendances en matiere de soins et du devenir des patients atteints de maladie thrombotique.

BACKGROUND: The clinical outcomes during the course of anticoagulation in patients with venous thromboembolism (VTE) using statins remain controversial. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the risk for VTE recurrences, major bleeding or death during anticoagulation, according to the use of statins at baseline. We used propensity score-matching (PSM) to adjust for confounding variables. RESULTS: From February 2009 to January 2018, 32,062 VTE patients were included. Of these, 7,085 (22%) were using statins. Statin users were 10 years older (73±11 vs. 63±19 years, respectively) and more likely to have comorbidities or to be using antiplatelets or corticosteroids at baseline than non-users. During the course of anticoagulation (median, 177 days), 694 patients developed VTE recurrences, 848 bled and 3,169 died (fatal pulmonary embolism 176, fatal bleeding 121). Statin users had a similar rate of VTE recurrences (hazard ratio [HR]: 0.98; 95%CI: 0.82-1.17), a higher rate of major bleeding (HR: 1.29; 95%CI: 1.11-1.50) and a similar mortality rate (HR: 1.01; 95%CI: 0.93-1.10) than non-users. On PSM analysis, statin users had a significantly lower risk for death (HR: 0.62; 95%CI: 0.48-0.79) and a similar risk for VTE recurrences (HR: 0.98; 95%CI: 0.61-1.57) or major bleeding (HR: 0.85; 95%CI: 0.59-1.21) than non-users. CONCLUSIONS: During anticoagulation for VTE, patients using statins at baseline had a lower risk to die than non-users. ispartof: EUROPEAN JOURNAL OF INTERNAL MEDICINE vol:68 pages:30-35 ispartof: location:Netherlands status: published

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

Background: Limited data exist about the clinical presentation and outcomes of patients with inferior vena cava agenesis (IVCA) who develop deep vein thrombosis (DVT). Methods: We used the RIETE (Registro Informatizado Enfermedad Trombo Embolica) registry to compare clinical characteristics and outcomes of patients with lower limb DVT, according to the presence or absence of IVCA. Major outcomes included recurrent DVT, major bleeding and post-thrombotic syndrome (PTS). Results: Among 50,744 patients with lower-limb DVT recruited in October 2018, 31 (0.06%) had IVCA. On multi-variable analysis, patients aged < 30 years (odds ratio [OR]: 17.9; 95%CI: 7.05-45.3), with unprovoked DVT (OR: 2.49; 95%CI: 1.17-5.29), proximal (OR: 2.81; 95%CI: 1.05-7.53) or bilateral DVT (OR: 11.5; 95%CI: 4.75-27.8) were at increased risk to have IVCA. Patients with DVT and IVCA had lower odds to present with coexisting PE (OR: 0.22; 95%CI: 0.07-0.73). During the first year of follow-up, the rates of DVT recurrences (hazard ratio [HR]: 1.30; 95%CI: 0.07-6.43), pulmonary embolism (HR: 2.30; 95%CI: 0.11-11.4) or major bleeding (HR: 1.32; 95%CI: 0.07-6.50) were not significantly different with those with versus those without IVCA. One year after the index DVT, IVCA patients had a higher rate of skin induration (OR: 3.70; 95%CI: 1.30-9.52), collateral vein circulation (OR: 3.57; 95%CI: 1.42-8.79) or venous ulcer (OR: 5.87; 95%CI: 1.36-1.87) in the lower limb than those without IVCA. Conclusions: Certain clinical features such as unprovoked and bilateral proximal DVT in young patients should raise the suspicion for IVCA. Patients with IVCA had higher odds for symptoms of post-thrombotic syndrome. (C) 2020 Elsevier B.V. All rights reserved.

This study uses Medicare billing codes to characterize trends in readmission and mortality rates for Medicare fee-for-service beneficiaries with pulmonary embolism (PE) between 1999 and 2015 to assess changes accompanying recent diagnostic and therapeutic changes in management of the disease.

The influence of morbid obesity on mortality in patients receiving anticoagulant therapy for VTE has not been consistently evaluated.Data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry were used to compare the mortality risk during anticoagulation in patients with VTE and morbid obesity (BMI ≥ 40 kg/mBy September 2018, there were 1,642 patients with VTE and morbid obesity and 14,848 with normal weight in RIETE. Of these, 245 (5.5%) and 1,397 (11.6%), respectively, had cancer. Median duration of anticoagulant therapy was longer in the morbidly obese patients, with cancer (185 vs 114 days) or without cancer (203 vs 177 days). Among cancer patients, 44 (18.0%) morbidly obese and 1,377 (32.8%) patients with normal weight died during anticoagulation. Among those without cancer, 44 (3.1%) morbidly obese died and 601 (5.6%) with normal weight died. On bivariate analysis, morbid obesity was associated with a lower mortality rate, both in patients with cancer (hazard ratio, 0.34; 95% CI, 0.25-0.45) and in those without cancer (hazard ratio, 0.43; 95% CI, 0.32-0.58). Multivariable analysis confirmed a lower hazard of death in morbidly obese patients with cancer (hazard ratio, 0.68; 95% CI, 0.50-0.94) and without cancer (hazard ratio, 0.67; 95% CI, 0.49-0.96). The risk for VTE recurrences or major bleeding did not differ in patients with or without morbid obesity.In patients with VTE, the risk for death during anticoagulation was about one-third lower in morbidly obese patients than in those with normal weight, independently of the presence of cancer.

Rationale: Acute kidney injury (AKI) is associated with a poor outcome. Although pulmonary embolism (PE) may promote AKI through renal congestion and/or hemodynamic instability, its frequency and influence on outcome in patients with acute PE have been poorly studied. Methods: The frequency of AKI (defined according to the “Kidney Disease: Improving Global Outcomes” definition) at baseline and its influence on the 30-day mortality was evaluated in patients with acute PE from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. We used multivariate analysis to assess whether the presence of AKI influenced the risk for 30-day death. Results: The study included 21,131 patients, of whom 6222 (29.5%) had AKI at baseline: 4385 patients (21%) in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. The proportion of patients with high-risk PE in those with no AKI, AKI stage 1, AKI stage 2 or AKI stage 3 was: 2.8%, 5.3%, 8.8% and 12%, respectively (p < 0.001). After 30 days, 1236 patients (5.9%) died. Overall mortality was 4% in patients with no AKI, 8.4% in AKI stage 1, 14% in AKI stage 2 and 17% in AKI stage 3 (all p < 0.001). AKI was independently associated with an increased risk of all-cause death at 30 days (odds ratio = 1.25; 95%CI: 1.02–1.54). Conclusions: One in every 3–4 patients with acute PE had AKI at baseline. The presence of AKI independently predicted 30-day mortality. This study suggests that AKI may deserve to be evaluated as a prognostic factor in patients with acute PE.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Vitamin K antagonists (VKA) remain the treatment of choice for catastrophic antiphosphilipid syndrome (CAPS). However, when VKAs do not work for a specific patient, direct oral anticoagulants (DOAC) may be a valid therapeutic alternative. We present a patient with a psychiatric disorder and CAPS who was noncompliant to VKA and low-molecular-weight heparin. He was started on dabigatran and has remained thrombosis-free for 8 years. Due to CAPS he has developed progressive renal failure but dabigatran levels were within the expected range. In conclusion, this case report provides anecdotic evidence that dabigatran may be of use in patients with high-risk APS in whom VKA are not an option.

[Objectives] To evaluate the association between experience in the management of acute pulmonary embolism, reflected by hospital case volume, and mortality., [Design] Multinational population based cohort study using data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry between 1 January 2001 and 31 August 2018., [Setting] 353 hospitals in 16 countries., [Participants] 39 257 consecutive patients with confirmed diagnosis of acute symptomatic pulmonary embolism., [Main] outcome measure Pulmonary embolism related mortality within 30 days after diagnosis of the condition., [Results] Patients with acute symptomatic pulmonary embolism admitted to high volume hospitals (>40 pulmonary embolisms per year) had a higher burden of comorbidities. A significant inverse association was seen between annual hospital volume and pulmonary embolism related mortality. Admission to hospitals in the highest quarter (that is, >40 pulmonary embolisms per year) was associated with a 44% reduction in the adjusted odds of pulmonary embolism related mortality at 30 days compared with admission to hospitals in the lowest quarter (, [Conclusions] In patients with acute symptomatic pulmonary embolism, admission to high volume hospitals was associated with significant reductions in adjusted pulmonary embolism related mortality at 30 days. These findings could have implications for management strategies.