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Thromb Haemost. 2019 Sep;119(9):1498-1507. doi: 10.1055/s-0039-1692425. Epub 2019 Jun 23.

Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry.

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Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan.
Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
Department of Cardiology, Kinki University Hospital, Osaka, Japan.
Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan.
Department of Cardiology, Japanese Red Cross Otsu Hospital, Otsu, Japan.
Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Department of Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan.
Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.
Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan.
Department of Cardiology, Osaka Saiseikai Noe Hospital, Osaka, Japan.
Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka, Japan.
Division of Cardiology, Shimada Municipal Hospital, Shimada, Japan.
Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
Department of Cardiology, Kishiwada City Hospital, Kishiwada, Japan.
Department of Cardiology, Tenri Hospital, Tenri, Japan.
Department of Cardiology, Nishikobe Medical Center, Kobe, Japan.
Division of Cardiology, Nara Hospital, Faculty of Medicine, Kinki University, Ikoma, Japan.
Department of Cardiology, Koto Memorial Hospital, Higashiomi, Japan.
Department of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan.



 There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients.


 The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153).


 During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23-4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51-3.59), anemia (HR, 1.75, 95% CI, 1.27-2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27-3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22-2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model.


 Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.


Conflict of interest statement

Y.Y. received lecture fees from Daiichi-Sankyo and Bristol-Myers Squibb. T.M. received lecture fees from Mitsubishi Tanabe Pharma and Pfizer Japan and consultant fees from Asahi Kasei, Bristol-Myers Squibb, and Boston Scientific. M.A. received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare, and Daiichi-Sankyo. Dr. Kimura serves as an advisory board member for Abbott Vascular and Terumo Company. Y.Y. reports personal fees from Daiichi-Sankyo, personal fees from Bristol-Myers Squibb, outside the submitted work; T.M. reports personal fees from Mitsubishi Tanabe Pharma, personal fees from Pfizer Japan, personal fees from Asahi Kasei, personal fees from Bristol-Myers Squibb, personal fees from Boston Scientific, outside the submitted work; M.A. reports personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Boehringer Ingelheim, personal fees from Bayer Healthcare, personal fees from Daiichi-Sankyo, outside the submitted work; T.K. reports personal fees from Abbott Vascular, personal fees from Terumo Company, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this article to disclose.

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