Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations

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

COVID-19–associated venous thromboembolism: risk of recurrence and major bleeding

© 2023 The Author(s). Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Complications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported.[Objectives] 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.[Methods] 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.[Results] 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.[Conclusion] 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.The study was supported by Sanofi Spain and ROVI with an unrestricted educational grant.Peer reviewe

Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry

Background: Venous thromboembolism (VTE)—including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)—may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4–30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018–2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7–94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07–47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding

Introduction: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. Methods: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. Results: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68–0.79) for major bleeding, 0.73 (95% CI: 0.67–0.78) for non-major bleeding and 0.82 (95% CI: 0.76–0.87) for bleeding-related death. Conclusions: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding

Introduction: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. Methods: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. Results: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68–0.79) for major bleeding, 0.73 (95% CI: 0.67–0.78) for non-major bleeding and 0.82 (95% CI: 0.76–0.87) for bleeding-related death. Conclusions: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding

Impact of sex, age, and risk factors for venous thromboembolism on the initial presentation of first isolated symptomatic acute deep vein thrombosis

BACKGROUND AND AIMS: Sex-specific differences exist for the initial presentation of acute venous thromboembolism (VTE): men are more likely to present with proximal deep vein thrombosis (DVT) in the lower limbs (versus pulmonary embolism [PE] or isolated distal DVT [IDDVT]) than women. We studied in detail the influence of sex, age, and VTE risk factors on the initial presentation of IDDVT versus proximal DVT. METHODS: A total of 24,911 patients with a first episode of objectively diagnosed acute symptomatic lower-limb DVT (without symptomatic PE) were enrolled in RIETE (years 2000-2017) and included in the present analysis. RESULTS: A total of 4266 (17.1%) patients had IDDVT. No trend for more IDDVT diagnoses was observed over time. Women aged 40-69 had a higher proportion of IDDVT, especially between 40 and 49 years (+6.7%; 95CI +3.7%; +9.9%), whereas men had more often proximal DVT. The presenting location of first acute DVT depended on sex, age, and the prevalence and type of VTE risk factors. Recent surgery was independently associated with a diagnosis of IDDVT in both women and men, whereas active cancer and pregnancy were associated with proximal DVT. CONCLUSIONS: The interaction between age and VTE risk factors influences the presenting location (distal versus proximal) of the first acute lower-limb DVT observed in women and men. Our observations extend to IDDVT the concept that different clinical manifestations of acute VTE may not fully share the same pathophysiological mechanisms: this contributes to explain sex-specific prognostic differences.status: publishe