Division of Emergency and Intensive Care Unit, 469340Shiga University of Medical Science Hospital, Otsu, Shiga, Japan.
Medical Affairs Division, 38481Asahi Kasei Pharma Corporation, Yurakucho, Chiyoda-ku, Tokyo, Japan.
Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221077096. doi: 10.1177/10760296221077096.
Thrombomodulin alfa (TM-α, recombinant human soluble thrombomodulin) and antithrombin (AT) concentrate are anticoagulant agents for the treatment of disseminated intravascular coagulation (DIC). A post hoc analysis using data from 1198 patients with infection-induced DIC from the post-marketing surveillance of TM-α was conducted. To identify subgroups that benefit from combination therapy, the patients were a priori stratified into four groups by a platelet (Plt) count of 50 × 10/μL and plasma AT level of 50% (groups 1, 2, 3, and 4, with high Plt/high AT, high Plt/low AT, low Plt/high AT, and low Plt/low AT, respectively). Kaplan-Meier survival analysis showed significantly worse survival in groups 2 and 4 had than in group 1 (p = 0.0480, p < 0.0001, respectively), and multivariate analysis showed that concomitant AT concentrate was independently correlated with reduced 28-day mortality only in group 4 (hazard ratio 0.6193; 95% confidence interval, 0.3912-0.9805). The adverse drug reactions (ADRs) and bleeding ADRs were not different among the groups. Patients with both severe thrombocytopenia and AT deficiency are candidates for combined anticoagulant therapy with TM-α and AT concentrate.
血栓调节蛋白 α（TM-α，重组人可溶性血栓调节蛋白）和抗凝血酶（AT）浓缩物是治疗弥漫性血管内凝血（DIC）的抗凝剂。对来自 TM-α上市后监测的 1198 例感染性 DIC 患者的数据进行了事后分析。为了确定从联合治疗中获益的亚组，根据血小板（Plt）计数为 50×10/μL 和血浆 AT 水平为 50%（高 Plt/高 AT、高 Plt/低 AT、低 Plt/高 AT 和低 Plt/低 AT 组 1、2、3 和 4）将患者预先分层。生存分析表明，与组 1 相比，组 2 和组 4 的生存显著较差（p=0.0480，p<0.0001），多变量分析表明，仅在组 4 中同时使用 AT 浓缩物与 28 天死亡率降低独立相关（危险比 0.6193；95%置信区间，0.3912-0.9805）。各组之间的不良反应（ADR）和出血 ADR 无差异。同时存在严重血小板减少和 AT 缺乏的患者是 TM-α和 AT 浓缩物联合抗凝治疗的候选者。
