Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - Safety and efficacy in 1,032 patients with hematologic malignancy

• Published in: Thrombosis research Vol. 133; no. 3; pp. 364 - 370
• Main Authors: Asakura, Hidesaku, Takahashi, Hoyu, Tsuji, Hajime, Matsushita, Tadashi, Ninomiya, Hideyuki, Honda, Goichi, Mimuro, Jun, Eguchi, Yutaka, Kitajima, Isao, Sakata, Yoichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2014
• Subjects: Adolescent; Adult; Aged; Child; Child, Preschool; Disseminated intravascular coagulation; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - drug therapy; Female; Hematologic malignancy; Hematologic Neoplasms - blood; Hematologic Neoplasms - drug therapy; Hematology, Oncology and Palliative Medicine; Humans; Infant; Infant, Newborn; Male; Middle Aged; Post-marketing surveillance; Product Surveillance, Postmarketing; Prospective Studies; Recombinant Proteins - adverse effects; Recombinant Proteins - blood; Recombinant Proteins - therapeutic use; Thrombomodulin; Thrombomodulin - blood; Thrombomodulin - therapeutic use; Young Adult; ALL; CLL; PT; JMHLW; TAT; Disseminated intravascular coagulation; SPI; ADR; LDH; FDP; WBC; Thrombomodulin; MDS; DIC; Post-marketing surveillance; AML; MM; CML; AE; PIC; JMHW; APTT; AT; Hematologic malignancy; SAE; TM; APL; prothrombin time; thrombin-antithrombin complex; acute myeloid leukemia; adverse drug reaction; Japan Ministry of Health, Labour, and Welfare; serious adverse event; plasmin α2-plasmin inhibitor complex; antithrombin; Japanese Ministry of Health and Welfare; disseminated intravascular coagulation; multiple myeloma; serine protease inhibitor; white blood cell; fibrin and fibrinogen degradation products; lactate dehydrogenase; adverse event; chronic myelogenous leukemia; acute promyelocytic leukemia; chronic lymphocytic leukemia; acute lymphoblastic leukemia; activated partial thromboplastin time; myelodysplastic syndromes; thrombomodulin
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2013.12.033

Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated. The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy.