Association between anticoagulant-related bleeding and mortality in patients with hematological malignancies and cancer-associated venous thromboembolism

INTRODUCTION: Patients with hematological malignancies are at an increased risk of severe bleeding. Anticoagulant (AC) therapy further increases this risk. Mortality after these bleeds is unclear and may differ by bleeding site. Aim To evaluate the association between bleeding and mortality in patients with hematological malignancies prescribed AC therapy for cancer-associated venous thromboembolism (VTE). METHODS: In a nationwide cohort of US Veterans (2012-2020), we identified patients with hematological malignancies and cancer-associated VTE prescribed AC therapy. Bleeding events were identified by a previously validated algorithm using hospitalization International Classification of Disease (ICD) codes. Within 12 months of AC therapy initiation, we evaluated the association between bleeding and mortality using multivariate Cox regression models, with AC-related bleeding analyzed as a time-varying covariate. RESULTS: The cohort included 1825 patients. Within 12 months of starting AC therapy, 123 (6.7 %) had bleeding events and 162 (8.9 %) patients died. Patients with bleeding events were more likely to have anemia, history of bleeding, aspirin use, chemotherapy use, and frailty. A multivariable Cox proportional-hazard model showed that AC-related bleeding was associated with tripled mortality rate (aHR 3.26, 95 % CI 1.96-5.45). When stratified by bleeding site, intracranial bleeding was associated with the highest risk of death (aHR 13.41, 95 % CI 4.13-43.48), followed by gastrointestinal bleeding (aHR 4.55, 95 % CI 2.48-8.35). CONCLUSION: In this cohort of patients with hematological malignancies and newly diagnosed VTE initiated on AC therapy, bleeding was associated with an increased risk of mortality within 12 months. Association was highest with intracranial and gastrointestinal bleeding.