The Japanese Society on Thrombosis and Hemostasis Post-marketing Surveillance Committee for Thrombomodulin Alfa, Japan.
Thromb Res. 2013 May;131(5):436-43. doi: 10.1016/j.thromres.2013.03.008. Epub 2013 Apr 6.
We assessed the safety and effectiveness of recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) in the treatment of disseminated intravascular coagulation (DIC) in a post-marketing surveillance.
The cases of 3548 patients with DIC caused by infection (n=2516, Infection-DIC) or hematological malignancy (n=1032, Hemat-DIC) were analyzed and compared to the results of a phase III (P-III) study.
The DIC scores were significantly decreased in the Infection-DIC and Hemat-DIC groups with TM-α treatment (both P<0.001). The incidences of critical bleeding adverse drug reactions (ADRs) in the Infection-DIC and Hemat-DIC groups were 2.6% and 2.4%, and the survival rates were 64.1% and 70.7%, respectively. Patients with DIC were subcategorized into three groups (Infection-DIC-1 or Hemat-DIC-1, P-III criteria-matched patients; Infection-DIC-2 or Hemat-DIC-2, P-III criteria-non-matched patients treated solely with TM-α; and Infection-DIC-3 or Hemat-DIC-3, P-III criteria-non-matched patients treated with TM-α and other concomitant anticoagulants). Subcategory analysis revealed that the incidences of critical bleeding ADRs of Hemat-DIC-2 and Hemat-DIC-3 were significantly higher and their survival rates were significantly lower than those of Hemat-DIC-1. By multivariate analysis in Hemat-DIC, younger age (odds ratio: 2.629, P=0.0033) and pre-existing bleeding (odds ratio: 2.044, P=0.019) were found to affect bleeding ADRs and the severity of underlying disease was the most important factor for survival rate (odds ratio: 0.288, P<0.001).
This surveillance provided real-world data for the safety and effectiveness of TM-α in the treatment of Infection-DIC and Hemat-DIC in general practice settings.
我们评估了重组可溶性血栓调节蛋白（血栓调节蛋白阿尔法，TM-α）在治疗弥漫性血管内凝血（DIC）的上市后监测中的安全性和有效性。
分析了 3548 例由感染（n=2516，感染性 DIC）或血液恶性肿瘤（n=1032，血液性 DIC）引起的 DIC 患者，并与 III 期（P-III）研究结果进行了比较。
TM-α治疗后，感染性 DIC 和血液性 DIC 组的 DIC 评分均显著降低（均 P<0.001）。感染性 DIC 和血液性 DIC 组严重出血不良反应（ADR）的发生率分别为 2.6%和 2.4%，生存率分别为 64.1%和 70.7%。将 DIC 患者分为三组（感染性 DIC-1 或血液性 DIC-1，符合 P-III 标准的患者；仅用 TM-α治疗的感染性 DIC-2 或血液性 DIC-2，不符合 P-III 标准的患者；不符合 P-III 标准的感染性 DIC-3 或血液性 DIC-3，用 TM-α和其他同时抗凝剂治疗的患者）。亚组分析显示，血液性 DIC-2 和血液性 DIC-3 的严重出血 ADR 发生率显著较高，生存率显著较低。在血液性 DIC 的多变量分析中，年龄较小（优势比：2.629，P=0.0033）和预先存在的出血（优势比：2.044，P=0.019）被发现影响出血 ADR，而基础疾病的严重程度是生存率的最重要因素（优势比：0.288，P<0.001）。
本监测提供了 TM-α在一般实践环境中治疗感染性 DIC 和血液性 DIC 的安全性和有效性的真实世界数据。
