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Purpose: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer., Methods: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT., Results: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58)., Conclusion: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Background:  The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers., Methods:  Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed., Results:  As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56-0.95), major bleeding (RR: 0.72; 95% CI: 0.53-0.98), or all-cause death (RR: 0.49; 95% CI: 0.41-0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes., Conclusion:  Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE)., Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT., Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection., Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE., Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%)., Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Background: Patients with pulmonary embolism (PE) who prematurely discontinue anticoagulant therapy (<90 days) are at an increased risk for death or recurrences., Methods: We used the data from the RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica) registry to compare the prognostic ability of five machine-learning (ML) models and logistic regression to identify patients at increased risk for the composite of fatal PE or recurrent venous thromboembolism (VTE) 30 days after discontinuation. ML models included decision tree, k-nearest neighbors algorithm, support vector machine, Ensemble, and neural network [NN]. A "full" model with 70 variables and a "reduced" model with 23 were analyzed. Model performance was assessed by confusion matrix metrics on the testing data for each model and a calibration plot., Results: Among 34,447 patients with PE, 1,348 (3.9%) discontinued therapy prematurely. Fifty-one (3.8%) developed fatal PE or sudden death and 24 (1.8%) had nonfatal VTE recurrences within 30 days after discontinuation. ML-NN was the best method for identification of patients experiencing the composite endpoint, predicting the composite outcome with an area under receiver operating characteristic (ROC) curve of 0.96 (95% confidence interval [CI]: 0.95-0.98), using either 70 or 23 variables captured before discontinuation. Similar numbers were obtained for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The discrimination of logistic regression was inferior (area under ROC curve, 0.76 [95% CI: 0.70-0.81]). Calibration plots showed similar deviations from the perfect line for ML-NN and logistic regression., Conclusion: The ML-NN method very well predicted the composite outcome after premature discontinuation of anticoagulation and outperformed traditional logistic regression., Competing Interests: None declared., (Thieme. All rights reserved.)

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Treatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding., Material and Methods: We used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline., Results: As of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had <50 × 10 9  platelets/L (severe thrombocytopenia), 711 (4.6%) had 50-99 × 10 9 /L (mild thrombocytopenia) and 14,460 (94.3%) had ≥100 × 10 9 /L (normal count). Most patients in all subgroups received initial therapy with low-molecular-weight heparin (LMWH), but 62% of those with severe thrombocytopenia received <150 IU/kg/day LMWH, 42% received <100 IU/kg/day. The mortality rate progressively decreased with increasing platelet counts (12%, 9.4% and 3.3% respectively at 10 days, 27%, 18% and 9.4% at 30 days), but the major bleeding rates did not (1.2%, 2.5% and 1.3% respectively at 10 days, 2.4%, 4.4% and 2.2% at 30 days). On multivariable analysis, patients with severe thrombocytopenia had a similar risk for major bleeding at 10 days (OR 0.84; 95%CI 0.20-3.49) and at 30 days (OR 0.90; 95%CI 0.32-2.49), but those with mild thrombocytopenia were at increased risk both at 10 days (OR 2.11; 95%CI 1.27-3.49) and at 30 days (OR 1.91; 95%CI 1.29-2.84)., Conclusions: Cancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared., Material and Methods: We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy., Results: From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06)., Conclusion: The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding., Competing Interests: Declaration of competing interest No potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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.

Background: Proper risk stratification of patients for early mortality after cancer-associated thrombosis may lead to personalized anticoagulation protocols. Therefore, we aimed to derive and validate a scoring system to predict early mortality in this population. To this end, we selected patients with active cancer and thrombosis from the Computerized Registry of Patients with Venous Thromboembolism database., Methods: The main outcome was all cause mortality within the month following a thrombotic event. We used a simple random selection to split are data in a derivation and a validation cohort. In the derivation cohort, we used recursive partitioning and binary logistic regression to identify groups at risk and to determine the likelihood of the primary outcome. The risk score was developed based on odds ratios from the final multivariate model, and then tested in the validation cohort., Results: In 10,025 eligible patients, we identified 6 predictors of 30-day mortality: leukocytosis ≥11.5x109/L; platelet count ≤160x109/L, metastasis, recent immobility, initial presentation as pulmonary embolism and Body Mass Index <18.5. The model divided the population into 3 risk categories: low (score 0-3), moderate (score 4-6), and high (score ≥7). The AUC for the overall score was 0.74, and using a cutoff ≥7 points, the model had a negative predictive value of 94.4%, a positive predictive value of 23.1%, a sensitivity of 73.3%, and a specificity of 64.6% in the validation cohort., Conclusions: Our validated risk model may assist physicians in the selection of patients for outpatient management, and perhaps anticoagulant, considering expanding anticoagulation options.

Background: Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined., Methods: The current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism)., Results: During the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n = 27) was similar to that related to pulmonary embolism recurrences (n = 26)., Conclusions: In this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting., (Copyright © 2018. Published by Elsevier Inc.)

Background: There 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 Methods: Registro Informatizado Enfermedad Trombo Embólica (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., Results: As of October 2014, 41 927 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 (8.3±8.8 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., Conclusion: Therapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.

Background and Objectives: There are a lot of venous thromboembolism risk assessment models with the aim of predicting the individual risk of venous thromboembolism (VTE), although most have not been externally validated. The objective of our study was to analyse the concordance among the Padua, PRETEMED, IMPROVE and MEDENOX scores., Patients and Methods: Observational cohort study with 602 patients admitted to Medical Services of the Hospital Universitario Santa Lucía. Concordance was calculated using the kappa index (KI) between the four risk prediction scales and the VTE occurring within 90 days of hospitalisation., Results: Patients considered were those with a high risk of VTE, 78%, 56%, 69% and 59% according to Padua, PRETEMED, IMPROVE and MEDENOX scores respectively. A KI=0.60 was observed among Padua-IMPROVE scores; KI=0.44 among IMPROVE-PRETEMED, KI=0.43 among PRETEMED-MEDENOX, KI=0.33 among Padua-PRETEMED, KI=0.27 among IMPROVE-MEDENOX and a KI=0.24 among Padua-MEDENOX. During follow-up, nine cases of VTE (1.5%) were observed., Conclusions: The highest degree of agreement was observed among the Padua and IMPROVE scores. There is no good agreement between any of the predictive risk scales for VTE in medical patients. The Padua score was the best predictor of VTE episodes at 90 days among high risk patients., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding and pregnant patients) have been under-represented in clinical trials. Furthermore, design of clinical trials is challenging in some scenarios, such as in those with hemodynamically unstable PE. RIETE ( R egistro I nformatizado E nfermedad T rombo E mbolica) is a large prospective multinational ongoing registry, designed to address these unmet needs using representative data from multiple centres. Initiated in Spain in 2001, RIETE currently includes 179 centres in 24 countries and has enrolled more than 72,000 patients. RIETE has helped characterize the pattern of presentation and outcomes of VTE, including the aforementioned understudied subgroups. RIETE has recently expanded to collect long-term outcome data, and has broadened its inclusion criteria to enrol other forms of venous thrombosis (such as cerebral vein thrombosis and splanchnic vein thrombosis). The RIETE platform is also being used to conduct pragmatic comparative effectiveness studies, including randomized trials. Future steps would focus on collaboration with additional centres across the world, and efforts to ensure the quality and expansion of the registry. In conclusion, RIETE is a large ongoing registry of patients with VTE and other thrombotic conditions. Its results could be helpful for improving our understanding of the epidemiology, patterns of care and outcomes of patients with thrombotic disease., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Schattauer GmbH Stuttgart.)

Background: The outcome of cancer patients with venous thromboembolism (VTE) may differ according to gender., Methods: We used the RIETE database to compare the rate of VTE recurrences, major bleeding and mortality in patients with lung, colorectal, pancreatic, hematologic or gastric cancer during the course of anticoagulation, according to gender., Results: As of January 2016, 11,055 patients with active cancer were enrolled: 1,727 had lung cancer, 1,592 colorectal, 840 hematologic, 517 pancreatic and 459 had gastric cancer. Compared with men (N = 3,130), women (N = 2,005) were more likely to have colorectal, pancreatic or hematologic cancer, and less likely to have lung cancer. Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH), but women received higher daily doses per body weight. Then, 66% kept receiving LMWH for long-term therapy. During the course of anticoagulation, 302 patients developed recurrent VTE, 220 bled and 1,749 died. Compared with men, women had a similar rate of VTE recurrences or major bleeding, and a lower mortality (risk ratio [RR]: 0.90; 95% CI: 0.82-0.99). When separately comparing outcomes according to cancer site, women with lung cancer had a lower mortality (RR: 0.79; 95% CI: 0.70-0.92), those with colorectal cancer had a higher mortality (RR: 1.25; 95% CI: 1.02-1.54) and those with gastric cancer had a higher rate of VTE recurrences than men (RR: 2.47; 95% CI: 1.04-5.89)., Conclusions: VTE women with lung, colorectal, pancreatic, haematological or gastric cancer experienced a similar outcome during the course of anticoagulant therapy than men with similar cancers., (© 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years 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., (© 2017 Elsevier Ltd. All rights reserved.)

In 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.

In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation.This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE.As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds.In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy.

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.

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.)

Background: Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice., Methods: We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer., Results: Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05)., Conclusions: An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Stratification of the individual bleeding risk prior to initiation of anticoagulation in patients with acute venous thromboembolism (VTE) has the potential to assist clinicians in making decisions about the proper intensity and duration of antithrombotic therapy. It is unclear which of the validated and internationally accepted scores recommended for the achievement of this important task has the best predictive value. We compared the predictive value of four validated scores (by Landefeld, Beyth, Kuijer and Ruiz-Gimenez, respectively) for the development of major bleeding complications occurring in the first 3 months in patients with acute VTE treated with conventional anticoagulation. Based on the population of RIETE Registry (international registry of patients with acute VTE), we identified those patients presenting all the required prognostic variables, and then calculated the ability of each score for predicting the bleeding risk. Of 40,265 eligible patients, we identified 8,717 meeting the recruitment criteria. Overall, 0.9 % of patients experienced at least one episode of major bleeding within 90 days of the index event. The proportion of patients classified as having a low risk varied between 1.2 and 3.7 %, that of patients having an intermediate risk between 76 and 93 %, and that of patients classified as having a high risk between 6.1 and 18 %. The area under the receiver operating characteristic ranged between 0.55 and 0.60, the positive predictive value between 1.5 and 3.2, and the likelihood ratio between 0.72 and 1.59. In conclusion, all four scores show a very low ability to predict the bleeding risk in patients with acute VTE undergoing conventional anticoagulation.

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<0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p<0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p<0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate., Conclusion: Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations., (Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In patients with acute venous thromboembolism and renal insufficiency, initial therapy with unfractionated heparin may have some advantages over low-molecular-weight heparin., Methods: We used the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Registry data to evaluate the 15-day outcome in 38,531 recruited patients. We used propensity score matching to compare patients treated with unfractionated heparin with those treated with low-molecular-weight heparin in 3 groups stratified by creatinine clearance levels at baseline: >60 mL/min, 30 to 60 mL/min, or <30 mL/min., Results: Patients initially receiving unfractionated heparin therapy (n = 2167) more likely had underlying diseases than those receiving low-molecular-weight heparin (n = 34,665). Propensity score-matched groups of patients with creatinine clearance levels >60 mL/min (n = 1598 matched pairs), 30 to 60 mL/min (n = 277 matched pairs), and <30 mL/min (n = 210 matched pairs) showed an increased 15-day mortality for unfractionated heparin compared with low-molecular-weight heparin (4.5% vs 2.4% [P = .001], 5.4% vs 5.8% [P = not significant], and 15% vs 8.1% [P = .02], respectively), an increased rate of fatal pulmonary embolism (2.8% vs 1.2% [P = .001], 3.2% vs 2.5% [P = not significant], and 5.7% vs 2.4% [P = .02], respectively), and a similar rate of fatal bleeding (0.3% vs 0.3%, 0.7% vs 0.7%, and 0.5% vs 0.0%, respectively). Multivariate analysis confirmed that patients treated with unfractionated heparin were at increased risk for all-cause death (odds ratio, 1.8; 95% confidence interval, 1.3-2.4) and fatal pulmonary embolism (odds ratio, 2.3; 95% confidence interval, 1.5-3.6)., Conclusions: In comparison with low-molecular-weight heparin, initial therapy with unfractionated heparin was associated with a higher mortality and higher rate of fatal pulmonary embolism in patients with creatinine clearance levels >60 mL/min or <30 mL/min, but not in those with levels between 30 and 60 mL/min., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose of Review: Cancer patients with venous thromboembolism (VTE) are at increased risk of mortality. Estimating the risks for specific causes of death may help to weigh the risks and benefits of different therapeutic strategies in an individual patient., Recent Findings: In the Registro Informatizado de la Enfermedad Trombo Embólica Registry of 15 520 consecutive patients with VTE, cancer was present in 20% and was associated with a two-fold increase in the risk of fatal pulmonary embolism. In a subsequent study including 2474 women with cancer, 329 (13%) died during the first month. The incidence of fatal pulmonary embolism (n = 71) exceeded that of fatal bleeding (n = 22), except in women with cancer of the bladder or vulva. Then, we compared the mortality rate according to initial presentation in 3978 women with cancer and VTE, of whom 438 (11%) died during the first month. The risk of fatal bleeding was twice as high as the risk of fatal pulmonary embolism (12 vs. 5 deaths) in those with deep-vein thrombosis alone., Summary: The higher risk of dying from bleeding than from pulmonary embolism in some women with cancer and VTE suggests that a less aggressive anticoagulant strategy might reduce fatal bleeding more than it would increase fatal pulmonary embolism during this period.

Long-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving ≥150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 ± 28), and 1,750 received ≥150 IU/kg/day (mean, 184 ± 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with ≥150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06-0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3-1.0) than those treated with ≥150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving ≥150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials.

Introduction: the development of venous thromboembolism (VTE) in patients with cancer adversely affects their prognosis. Several autopsy- and population-based studies have clearly shown a negative impact of VTE on patient outcome in cancer patients., Areas Covered: an up-to-date review of VTE prophylaxis and treatment in cancer patients is provided with some insights on areas of uncertainty to be answered in the near future. Particular attention is paid to recent cohort studies, randomized clinical trials and consensus guidelines., Expert Opinion: cancer patients at a higher risk for VTE may be identified with five variables easily available before initiation of chemotherapy. Long-term treatment with low-molecular-weight heparin (LMWH) demonstrated a superior efficacy over vitamin K antagonists. The intensity and duration of anticoagulant therapy should be tailored to the risk of VTE recurrences or bleeding in an individual patient.

The influence of the site of cancer on outcome in cancer women with venous thromboembolism (VTE) is poorly understood. Reliable information on its influence might facilitate better use of prevention strategies. We assessed the 30-day outcome in all women with active cancer in the RIETE Registry, trying to identify if differences exist according to the tumor site. Up to May 2010, 2474 women with cancer and acute VTE had been enrolled. The most common sites were the breast (26%), colon (13%), uterus (9.3%), and haematologic (8.6%) cancers. During the 30-day study period, 329 (13%) patients died. Of them, 71 (2.9%) died of pulmonary embolism (PE), 22 (0.9%) died of bleeding. Fatal PE was more common in women with breast, colorectal, lung or pancreatic cancer (59% of the fatal PEs). Fatal bleeding was more frequent in women with colorectal, haematologic, ovarian cancer or carcinoma of unknown origin (55% of fatal bleedings)., (© 2011 Elsevier Ltd. All rights reserved.)

Background: The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied., Methods: RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE., Results: As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; p<0.001) or with negative testing (31% vs. 45%, p<0.001). In addition, PE patients with Factor V Leiden presented with hypoxaemia (Sat O(2) levels<90%) less likely than those with prothrombin G20210A (4.5% vs. 17%; p<0.001) or with no thrombophilia (4.5% vs. 20%; p<0.001)., Conclusions: Most VTE episodes in women (not men) with factor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Cancer patients with venous thromboembolism (VTE) have an increased incidence of bleeding complications while on anticoagulant therapy., Methods: RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for major bleeding., Results: Up to May 2009, 4,709 patients with active cancer had been enrolled in RIETE registry. During the first 3 months of anticoagulant therapy, 200 (4.2%) patients developed major bleeding. Then, 38 (0.8%) further patients bled beyond the first 90 days of therapy, 3 bled after withholding anticoagulant therapy. The most common sites of bleeding were the gastrointestinal tract (118 patients, 49%), genitourinary system (43 patients, 18%) and the brain (27 patients, 11%). In all, 160 patients (66%) died within 30 days after bleeding: 88 (55%) died of bleeding, 3 (1.9%) died of recurrent pulmonary embolism., Conclusions: Major bleeding is a frequent and severe complication in cancer patients with VTE, even beyond the third month. One third of the patients who bled died due the bleeding event.

The balance between the efficacy and safety of anticoagulant therapy in patients aged >/=90 years with venous thromboembolism (VTE) is uncertain. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We evaluated the efficacy and safety of anticoagulant therapy during the first three months in all patients aged >/=90 years. In addition, we tried to identify those at a higher risk for VTE. Of 21,873 patients enrolled from March 2001 to February 2008, 610 (2.8%) were aged >/=90 years. Of these, 307 (50%) presented with pulmonary embolism (PE), 240 (39%) had immobility >/=4 days, and 271 (44%) had abnormal creatinine levels. During the first three months of therapy, 140 patients aged >/=90 years (23%) died. Of these, 45 (32%) died of PE (34 of the initial episode, 11 of recurrent PE), 18 (13%) had fatal bleeding. Recent immobility >/=4 days was the most common risk factor for VTE (240 of 610 patients, 39%), but only 54 of them (22%) had received thromboprophylaxis. The most frequent causes for immobility were senile dementia, acute infection, trauma or decompensated heart failure. The duration of immobility was <4 weeks in 126 patients (52%), and most of them were bedridden at home. In conclusion, one in every four VTE patients aged >/=90 years died during the first three months of therapy. Of these, one in every three died of PE, one in every eight had fatal bleeding. Identifying at-risk patients may help to prevent some of these deaths.

There is scarce information on the clinical characteristics of contraceptive users who develop venous thromboembolism (VTE). RIETE is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We analyzed the clinical characteristics and additional risk factors for VTE in all enrolled women aged <50 years who were using or not using contraceptives at presentation with VTE. Of 1,667 women aged <50 years enrolled in RIETE as of December 2007, 593 (36%) were contraceptive users. Of 270 aged <25 years, 190 (70%) were users. Ninety-two contraceptive users (16%) had overweight, 89 (15%) were obese. Of 951 women with no additional risk factors for VTE (i.e. recent surgery, immobility or cancer) 457 (48%) were contraceptive users. Eighty-seven (15%) users had recent immobility for >/=4 days, 44 (7.4%) were postoperative. The most common reason for immobility was lower limb trauma not requiring surgery; 25% of users with recent immobility had received thromboprophylaxis. The most common type of surgery was non-major orthopaedic surgery. Twenty-one (48%) users with postoperative VTE had received prophylaxis. The percentage of users and non-users who tested positive for thrombophilia was similar. Contraceptive use remains the most frequent risk factor for VTE in women at fertile age. Identifying those at increased risk for VTE seems to be difficult. In the meanwhile, a higher use of thromboprophylaxis during immobility or minor surgery should be warranted.

Patients with venous thromboembolism (VTE) and active cancer are often excluded from clinical trials of anticoagulant therapy because of short life expectancy, inability or unwillingness to attend for regular laboratory monitoring during vitamin K antagonist therapy, or contraindications to therapy. As such, treatment regimens based on the results from clinical trials might not be suitable for many VTE patients with cancer. 'Registro Informatizado de la Enfermedad TromboEmbólica' (RIETE) was initiated in March 2001 to prospectively record the current clinical management of patients with symptomatic, objectively confirmed, acute VTE in Spanish hospitals. This chapter will summarize the most important findings published to date regarding the association between VTE and cancer.

Background: Cancer patients with venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications Reliable information on the factors determining the risk for such complications may facilitate better use of therapy., Methods: RIETE Registry is an ongoing, international registry of consecutive patients presenting with symptomatic acute VTE confirmed by objective tests. We assessed the 3-month outcome in all women with active cancer, trying to identify if differences exist according to the tumor site., Results: Up to May 2007, 18,883 patients had been enrolled. Of them, 3805 (20%) had active cancer, 1719 (45%) were women. During the 3-month study period, 40 (2.3%) had recurrent deep vein thrombosis, 39 (2.3%) recurrent pulmonary embolism (PE), 67 (3.9%) major bleeding, 394 (23%) died. Of these, 13 (33%) women with recurrent PE died of the PE, 17 (42%) with major bleeding had fatal bleeding. In women with gastrointestinal (5.7% vs. 4.3%) or genitourinary (6.4% vs. 4.7%) cancers the incidence of bleeding complications exceeded that of VTE recurrences, while in those with brain (3.4% vs. 13%) or lung cancer (2.6% vs. 11%) the rate of recurrences outweighed that of major bleeding., Conclusions: We identified significant differences in outcome according to the site of cancer that may help to identify those women with cancer and VTE at a higher risk for recurrences or major bleeding.

A significant association between elevated white blood cell (WBC) count and mortality in patients with cancer has been reported, but the predictive value of elevated WBC on mortality in cancer patients with acute venous thromboembolism (VTE) has not been explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the three-month outcome of cancer patients with acute VTE according to their WBC count at baseline. As of May 2007, 3805 patients with active cancer and acute VTE had been enrolled in RIETE. Of them, 215 (5.7%) had low- (<4,000 cells/microl), 2,403 (63%) normal- (4,000-11,000 cells/microl), 1,187 (31%) elevated (>11,000 cells/microl) WBC count. During the study period 190 patients (5.0%) had recurrent VTE, 156 (4.1%) major bleeding, 889 (23%) died (399 of disseminated cancer, 113 of PE, 46 of bleeding. Patients with elevated WBC count at baseline had an increased incidence of recurrent VTE (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2-2.2), major bleeding (OR: 1.5; 95% CI: 1.1-2.1) or death (OR: 2.7; 95% CI: 2.3-3.2). Most of the reported causes of death were significantly more frequent in patients with elevated WBC count. Multivariate analysis confirmed that elevated WBC count was independently associated with an increased incidence of all three complications. In conclusion, cancer patients with acute VTE and elevated WBC count had an increased incidence of VTE recurrences, major bleeding or death. This worse outcome was consistent among all subgroups and persisted after multivariate adjustment.

Cancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3,805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9-4.9), with PE at entry (OR: 1.9; 95% CI: 1.2-3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2-3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0-2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5-3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2-2.7), metastases (OR: 1.6; 95% CI: 1.1-2.3), recent bleeding (OR: 2.4; 95% CI: 1.1-5.1), or with creatinine clearance <30 ml/min (OR: 2.2; 95% CI: 1.5-3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients with VTE at a higher risk for recurrences or major bleeding.