Benefit Profile of Thrombomodulin Alfa Combined with Antithrombin Concentrate in Patients with Sepsis-Induced Disseminated Intravascular Coagulation.

Abstract

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 × 103/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.