Tomoyuki Nagai, Naohiko Nakanishi, Yugo Yamashita, Takeshi Morimoto, Seiichi Hiramori, Ryuki Chatani, Yuji Nishimoto, Nobutaka Ikeda, Yohei Kobayashi, Satoshi Ikeda, Kitae Kim, Masayuki Shiba, Toru Takase, Shuhei Tsuji, Maki Oi, Takuma Takada, Kazunori Otsui, Jiro Sakamoto, Yoshito Ogihara, Takeshi Inoue, Shunsuke Usami, Po-Min Chen, Kiyonori Togi, Norimichi Koitabashi, Kosuke Doi, Hiroshi Mabuchi, Yoshiaki Tsuyuki, Koichiro Murata, Kensuke Takabayashi, Hisato Nakai, Daisuke Sueta, Wataru Shioyama, Tomohiro Dohke, Takeshi Kimura, Satoaki Matoba, Kazuhisa Kaneda, Ryusuke Nishikawa, Yugo Yamashita, Ryuki Chatani, Kazunori Mushiake, Kazushige Kadota, Yuji Nishimoto, Yukihito Sato, Nobutaka Ikeda, Katsushi Amemiya, Masato Nakamura, Yohei Kobayashi, Ren Kimura, Tsukasa Inada, Satoshi Ikeda, Yuki Ueno, Koji Maemura, Kitae Kim, Ryo Shigeno, Yutaka Furukawa, Moriaki Inoko, Shinya Ito, Toru Takase, Gaku Nakazawa, Shuhei Tsuji, Mamoru Toyofuku, Maki Oi, Kazuaki Kaitani, Takuma Takada, Kentaro Jujo, Nobuhisa Hagiwara, Kazunori Otsui, Kenta Mori, Jiro Sakamoto, Toshihiro Tamura, Yoshito Ogihara, Toru Sato, Kaoru Dohi, Takeshi Inoue, Tetsuya Nadahama, Kunihiko Kosuga, Shunsuke Usami, Katsuhisa Ishii, Po-Min Chen, Toshiaki Izumi, Kiyonori Togi, Manabu Shirotani, Takafumi Yokomatsu, Norimichi Koitabashi, Hideki Ishii, Seiichi Hiramori, Kenji Ando, Kosuke Doi, Masaharu Akao, Hiroshi Mabuchi, Yoshiaki Tsuyuki, Hiroto Yamamoto, Takeshi Aoyama, Koichiro Murata, Eri Ishikawa, Ryuzo Nawada, Kensuke Takabayashi, Mitsunori Miho, Shoji Kitaguchi, Takeshi Kimura
BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at a high risk of major bleeding during anticoagulant therapy, emphasizing the need for bleeding risk assessment in the era of direct oral anticoagulants (DOACs). However, few bleeding risk scores have been specifically developed and validated for this population. OBJECTIVES: The aim of this study was to develop and validate a novel bleeding risk score (ONCO-DOAC BLEED score) for patients with cancer-associated VTE receiving DOAC therapy. METHODS: We derived the bleeding risk prediction score using 1,166 patients with cancer-associated VTE treated with DOAC therapy from the COMMAND VTE (Contemporary Management and Outcomes in Patients with Venous Thromboembolism) Registry-2 and externally validated its performance in an independent cohort from the ONCO deep vein thrombosis and ONCO pulmonary embolism studies. RESULTS: Over a median follow-up of 163 days, 127 patients (10.9%) experienced major bleeding. In multivariable analysis, a history of major bleeding, chronic kidney disease, nonsteroidal anti-inflammatory drug use, distant metastatic cancer, terminal cancer, upper gastrointestinal cancer, pancreatic cancer, and uterine cancer were independently associated with major bleeding. Based on these risk factors, the ONCO-DOAC BLEED score was constructed. This score demonstrated moderate discrimination for major bleeding in the derivation cohort (Harrell's C-index 0.68; Uno's C-index 0.67) and validation cohort (Harrell's C-index 0.62; Uno's C-index 0.63), with higher discrimination in the derivation cohort and comparable performance in the validation cohort compared with the VTE-BLEED, RIETE, CAT-BLEED, and Perform scores. CONCLUSIONS: The ONCO-DOAC BLEED score provides clinically relevant stratification of major bleeding risk in patients with cancer-associated VTE receiving DOAC therapy and may support individualized therapeutic decision-making in routine practice. (Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study [ONCO DVT]; NCT03895502 and Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer [ONCO PE]; NCT04724460).