Behnood Bikdeli1, Fares Moustafa2, José Antonio Nieto3, Alfred I Lee4, Nuria Ruíz-Giménez5, Alicia Lorenzo6, Sebastian Schellong7, Silvia Soler8, Salvador Ortíz9, Mª Del Valle Morales10, Marijan Bosevski11, Olga Gavín12, Gregory Y H Lip13, Manuel Monreal14. 1. Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, USA; Center for Outcomes Research and Evaluation, Yale School of Medicine, New Haven, USA; Cardiovascular Research Foundation (CRF), New York, NY, USA. Electronic address: Behnood.bikdeli@yale.edu. 2. Department of Emergency, Clermont-Ferrand University Hospital, Clermont-Ferrand, France. 3. Department of Internal Medicine, Hospital Virgen de la Luz, Cuenca, Spain. 4. Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, USA. 5. Department of Internal Medicine, Hospital Universitario de La Princesa, Madrid, Spain. 6. Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain. 7. Department of Medical Clinic, Municipal Hospital of Dresden Friedrichstadt, Dresden, Germany. 8. Department of Internal Medicine, Hospital Olot i Comarcal de la Garrotxa, Gerona, Spain. 9. Universidad Autónoma Madrid, S&H Medical Science Service, Madrid, Spain. 10. Department of Internal Medicine, Hospital del Tajo, Madrid, Spain. 11. Institute for Cardiovascular Diseases, Faculty of Medicine, Clinical Center, Skopje, Macedonia. 12. Department of Haematology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. 13. Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Thrombosis Research Unit, Aalborg University, Aalborg, Denmark. 14. Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Universidad Autónoma de Barcelona, Spain.
Abstract
BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).
BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).
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