Summary
Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica ...(RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE‐BLEED scores were used for comparisons. External validation was performed with the COMMAND‐VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE‐BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE‐BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE‐BLEED scores only in the prospective validation cohort, but not in the external validation cohort.
While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain ...understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (
P
< 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.
Background
Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe ...and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years.
Methods
We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.
Results
From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths).
Conclusions
In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.
The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding.
Analyze rates and ...case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation.
We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding.
Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio HR, 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding.
Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.
Background
The diagnostic strategy for pulmonary embolism (PE) includes a D‐dimer test when PE probability is low or intermediate, but false‐positive D‐dimer results are frequent and can result in an ...unnecessary computed tomography pulmonary angiogram. The PE rule‐out criteria (PERC) rule excludes PE without D‐dimer testing when pretest probability is <15%. The aim of this study was to assess the safety of the PERC rule strategy in patients included in the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry.
Methods
This retrospective cohort study used data from the RIETE registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the failure rate of the PERC strategy, represented by the proportion of PERC‐negative (PERC‐N) patients with a PE included in the registry. Secondary outcomes were a comparison of the clinical characteristics, treatment strategy, and outcome of PERC‐N versus PERC‐positive (PERC‐P) patients at 3 months.
Results
From 2001 to 2021, a total of 49,793 patients with acute PE were enrolled in the RIETE registry. We included 48,903 in the final analysis after exclusion of 890 patients with an undetermined PERC status. Only 346 patients were PERC‐N with a failure rate of 0.7% (95% confidence interval 0.6%–0.8%). PERC‐N patients presented more frequently with chest pain but less often with dyspnea, syncope, or hypotension. They also had subsegmental or segmental PE more frequently, were more often treated with direct oral anticoagulants, and received mechanical or pharmacological thrombolysis less often. In addition, PERC‐N patients had a lower incidence of recurrent deep vein thrombosis, major bleeding, and death attributed to PE during the 3‐month follow‐up.
Conclusions
A low failure rate of the PERC rule was observed in the RIETE registry, thus supporting its use to safely identify patients with an unlikely probability of PE.
•In a RIETE registry analysis of 103 818 patients with VTE, 20.3% were tested for IT, showing a substantial variance in outcomes.•A thoughtful IT testing approach should consider patients’ VTE risk ...factors and comorbidities.
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Inherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245.
Complications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported.
This study aimed to compare the 90-day rates of VTE ...recurrences and major bleeding in patients with COVID-19-associated VTE versus those with VTE without COVID-19.
We used the RIETE registry to compare the 3-month outcomes in patients with COVID-19-associated VTE versus those with VTE without COVID-19.
The study included 1,747 patients with COVID-19-associated VTE and 8,711 with VTE without COVID-19. Patients with COVID-19-associated VTE were more likely to be hospitalized at baseline and to present with pulmonary embolism. During the first 90 days, 123 patients (1.17%) developed VTE recurrences, and 266 (2.54%) experienced major bleeding. Patients with COVID-19-associated VTE had a similar rate of VTE recurrences (0.9% vs 1.2%) but a higher rate of major bleeding (4.6% vs 2.1%; P < .001) than those without COVID-19. Multivariable analysis adjusted for competing risks showed that patients with COVID-19-associated VTE had an increased risk of major bleeding (subhazard ratio, 1.395; 95% confidence interval, 1.037-1.877). The 30-day mortality after major bleeding was 26.3% in patients with COVID-19-associated VTE and 17.7% in those without COVID-19.
Patients with COVID-19-associated VTE had a 5-fold higher rate of major bleeding than VTE recurrences during the first 90 days of anticoagulation. In VTE patients without COVID-19, both rates were similar. These findings highlight the importance of carefully monitoring and optimizing anticoagulation in these patients.
•Complications of anticoagulation in COVID-19-venous thromboembolism (VTE) have not been reported.•Patients with COVID-19-VTE versus patients with VTE without COVID-19 from the RIETE registry were included.•In COVID-19-associated VTE, the risk of major bleeding far outweighed the risk of VTE recurrences.•COVID-19–associated VTE had increased rates of hemoptysis, retroperitoneal, or muscular bleeding.
