Takao Kobayashi1, Masahiro Kajiki2, Katsuhito Nihashi3, Goichi Honda2. 1. Department of Obstetrics and Gynecology, Hamamatsu Medical Center, 328 Tomitsuka-cho, Naka-ku, Hamamatsu, Shizuoka 432-8580, Japan. Electronic address: tkoba@hmedc.or.jp. 2. Medical Affairs Department, Pharmaceuticals Business Administration Division, Asahi Kasei Pharma Corporation, 1-105 Kanda, Jinbocho, Chiyoda-ku, Tokyo 101-8101, Japan. 3. Post-Marketing Surveillance Department, Regulatory Affairs and Reliability Assurance Center, Asahi Kasei Pharma Corporation, 1-105 Kanda, Jinbocho, Chiyoda-ku, Tokyo 101-8101, Japan.
Abstract
BACKGROUND: Recombinant human soluble thrombomodulin (TM-α) has been shown to be useful in the treatment of disseminated intravascular coagulation (DIC) in a heparin-controlled study, and has been available for clinical use in Japan since 2008. However, use of TM-α for obstetrical DIC has not yet been established, so efficacy and safety were analyzed in 117 obstetrical DIC patients identified from post-marketing surveillance. MATERIALS AND METHODS: From June 2010 to March 2012, the cases of 117 patients with obstetrical DIC treated with TM-α were registered. RESULTS: In the majority of cases, the underlying disease was DIC-type postpartum hemorrhage (n=43) or placental abruption (n=37). Mean (±standard deviation) obstetrical DIC score was 10.6±4.9. Mean duration of TM-α administration was 2.2±1.7days. The most commonly used concomitant anticoagulants were antithrombin (n=60) and gabexate mesilate (n=37). Concomitantly used blood components products included red blood cell concentrate (n=72), fresh frozen plasma (n=70), and platelet concentrate (n=31). Hemostatic test result profiles revealed significant improvement of fibrinogen/fibrin degradation products, D-dimer, fibrinogen, prothrombin time and activated partial thromboplastin time. Efficacies of TM-α as evaluated by "The efficacy evaluation criteria for DIC in obstetrics" at 24h, 48h and the day after last administration of TM-α were 72.3%, 82.4% and 90.2%, respectively. Total bleeding adverse drug reactions occurred in 6 patients (5.1%). CONCLUSIONS: This surveillance confirmed the safety and efficacy of TM-α in clinical practice. These findings thus indicated that the efficacy of TM-α is comparable to that of previously investigated obstetrical DIC pharmacotherapies.
BACKGROUND: Recombinant human soluble thrombomodulin (TM-α) has been shown to be useful in the treatment of disseminated intravascular coagulation (DIC) in a heparin-controlled study, and has been available for clinical use in Japan since 2008. However, use of TM-α for obstetrical DIC has not yet been established, so efficacy and safety were analyzed in 117 obstetrical DIC patients identified from post-marketing surveillance. MATERIALS AND METHODS: From June 2010 to March 2012, the cases of 117 patients with obstetrical DIC treated with TM-α were registered. RESULTS: In the majority of cases, the underlying disease was DIC-type postpartum hemorrhage (n=43) or placental abruption (n=37). Mean (±standard deviation) obstetrical DIC score was 10.6±4.9. Mean duration of TM-α administration was 2.2±1.7days. The most commonly used concomitant anticoagulants were antithrombin (n=60) and gabexate mesilate (n=37). Concomitantly used blood components products included red blood cell concentrate (n=72), fresh frozen plasma (n=70), and platelet concentrate (n=31). Hemostatic test result profiles revealed significant improvement of fibrinogen/fibrin degradation products, D-dimer, fibrinogen, prothrombin time and activated partial thromboplastin time. Efficacies of TM-α as evaluated by "The efficacy evaluation criteria for DIC in obstetrics" at 24h, 48h and the day after last administration of TM-α were 72.3%, 82.4% and 90.2%, respectively. Total bleeding adverse drug reactions occurred in 6 patients (5.1%). CONCLUSIONS: This surveillance confirmed the safety and efficacy of TM-α in clinical practice. These findings thus indicated that the efficacy of TM-α is comparable to that of previously investigated obstetrical DIC pharmacotherapies.