Thromb Haemost
DOI: 10.1055/s-0039-1692425
Stroke, Systemic, or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

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

Kitae Kim
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Yugo Yamashita
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Takeshi Morimoto
3  Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
,
Takeshi Kitai
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Takafumi Yamane
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Natsuhiko Ehara
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Makoto Kinoshita
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Shuichiro Kaji
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Hidewo Amano
4  Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan
,
Toru Takase
5  Department of Cardiology, Kinki University Hospital, Osaka, Japan
,
Seiichi Hiramori
6  Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan
,
Maki Oi
7  Department of Cardiology, Japanese Red Cross Otsu Hospital, Otsu, Japan
,
Masaharu Akao
8  Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Yohei Kobayashi
9  Department of Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan
,
Mamoru Toyofuku
10  Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
,
Toshiaki Izumi
11  Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
,
Tomohisa Tada
12  Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan
,
Po-Min Chen
13  Department of Cardiology, Osaka Saiseikai Noe Hospital, Osaka, Japan
,
Koichiro Murata
14  Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka, Japan
,
Yoshiaki Tsuyuki
15  Division of Cardiology, Shimada Municipal Hospital, Shimada, Japan
,
Syunsuke Saga
16  Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
,
Tomoki Sasa
17  Department of Cardiology, Kishiwada City Hospital, Kishiwada, Japan
,
Jiro Sakamoto
18  Department of Cardiology, Tenri Hospital, Tenri, Japan
,
Minako Kinoshita
19  Department of Cardiology, Nishikobe Medical Center, Kobe, Japan
,
Kiyonori Togi
20  Division of Cardiology, Nara Hospital, Faculty of Medicine, Kinki University, Ikoma, Japan
,
Hiroshi Mabuchi
21  Department of Cardiology, Koto Memorial Hospital, Higashiomi, Japan
,
Kensuke Takabayashi
22  Department of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan
,
Hiroki Shiomi
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Takao Kato
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Takeru Makiyama
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Koh Ono
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
Yutaka Furukawa
1  Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
,
Takeshi Kimura
2  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
,
On behalf of the COMMAND VTE Registry Investigators› Author Affiliations
Funding The COMMAND VTE Registry is supported by the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan) and research funding from Mitsubishi Tanabe Pharma Corporation. The research funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Further Information

Publication History

10 October 2018

17 April 2019

Publication Date:
23 June 2019 (eFirst)

Abstract

Background 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.

Patients and Methods 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).

Results 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.

Conclusion 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.

Supplementary Material