Abstract
Background Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis
or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized
controlled trial, was completed.
Objective This article assesses the benefits and harms of rhTM therapy in sepsis-induced coagulopathy
by updating our previous systematic review.
Methods We performed a systematic review and meta-analysis of rhTM therapy for sepsis-induced
coagulopathy in randomized controlled trials. All-cause 28-day mortality as efficacy
and serious bleeding complications as the adverse effect were measured as primary
outcomes. We assessed the certainty of a body of evidence at the outcome level using
the Grading of Recommendations Assessment, Development and Evaluation approach.
Results We analysed five trials enrolling 1,762 patients. Approximately 13% reduction in
the risk of mortality was observed in the rhTM group, but the difference was not significant
(relative risk, 0.87; 95% confidence interval, 0.74–1.03; p = 0.10; I
2 = 0%). Risk of serious bleeding complications did not increase with rhTM administration.
We judged the certainty of evidence as moderate for mortality and low for serious
bleeding. Trial sequential analysis indicated that only 42.0% of the required information
size is actually available at this stage to reject or accept low risk-of-bias trials
examining the anticipated effect for all-cause mortality.
Conclusion Even in this updated review including the latest SCARLET trial, we currently cannot
make any declarative judgments about the beneficial effects of rhTM in sepsis-induced
coagulopathy, although some favourable effects were suggested.
Keywords
anticoagulants - coagulopathy - critically ill - disseminated intravascular coagulation
- septic shock
