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 (Registro Informatizado Enfermedad TromboEmbolica) 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.

Summary. Background: Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain. Methods: Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient’s risk of fatal bleeding during the first 3 months of treatment. Results: Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility ≥ 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 × 10⁹ L⁻¹ (OR, 2.23), creatinine clearance < 30 mL min⁻¹ (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11–0.23) of the low-risk, 1.06% (95% CI, 0.85–1.30) of the moderate-risk, and 4.24% (95% CI, 2.76–6.27) of the high-risk category. Conclusions: Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.

Summary: Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17–1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66–1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28–1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.

Summary: 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 patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.