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

Introduction: Post-marketing surveillance of thrombomodulin alfa (TM-alpha) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. Materials and methods: All patients treated with TM-alpha 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-alpha administration, and changes in DIC score and coagulation tests were evaluated. Results: 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-alpha 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-alpha treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. Conclusions: This surveillance confirmed the safety and efficacy of TM-alpha in clinical practice, thus TM-alpha may be an ideal treatment for patients with DIC based upon hematologic malignancy. (C) 2014 Elsevier Ltd. All rights reserved.