Premium
Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta‐analysis
Author(s) -
Yamakawa K.,
Aihara M.,
Ogura H.,
Yuhara H.,
Hamasaki T.,
Shimazu T.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12841
Subject(s) - medicine , observational study , thrombomodulin , randomized controlled trial , sepsis , meta analysis , disseminated intravascular coagulation , placebo , relative risk , adverse effect , retrospective cohort study , confidence interval , thrombin , pathology , platelet , alternative medicine
Summary Background Although recombinant human soluble thrombomodulin (rh TM ) is a widely used novel anticoagulant agent for disseminated intravascular coagulation ( DIC ) in Japan, its clinical efficacy in sepsis‐induced DIC has not been demonstrated convincingly. Objective To assess the benefits and harms of rh TM in sepsis‐induced DIC patients. Methods We conducted a systematic review and meta‐analysis of rh TM therapy for sepsis‐induced DIC for both randomized controlled trials ( RCT s) and observational studies (retrospective case‐control studies and/or prospective cohort studies) separately. All‐cause mortality (28–30 days) as efficacy and serious bleeding complications as adverse effect were measured as primary outcomes. We assessed body of evidence quality at the outcome level by using the G rading of E vidence, A ssessment, D evelopment and E valuation ( GRADE ) approach. Results We analyzed 12 studies (838 patients/3 RCT s; 571 patients/9 observational studies). Pooled relative risk was 0.81 (95% CI , 0.62–1.06) in the RCT s, indicating non‐significant reduction in mortality, and 0.59 (95% CI , 0.45–0.77) in the observational studies. Meta‐regression analysis revealed a significant negative slope between effect size of rh TM therapy and baseline mortality rate in individual studies ( P = 0.012), suggesting that probability of a beneficial effect with rh TM therapy increases with increasing baseline risk. Risk of serious bleeding complications was not significantly different between rh TM and control groups. We judged the quality of evidence as moderate for mortality and serious bleeding. Conclusions The rhTM was associated with a trend in reduction of mortality at 28–30 days in sepsis‐induced DIC patients. Further large rigorous trials are needed to confirm or refute these findings before implications for practice are clear.