Recombinant human soluble thrombomodulin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: An observational nationwide study

Abstract

Summary: Background: The association between recombinant human soluble thrombomodulin (rhTM) use and mortality in patients with sepsis-associated disseminated intravascular coagulation (DIC) remains controversial. Objectives: To examine the hypothesis that rhTM could be effective in the treatment of patients with sepsis-associated DIC following severe pneumonia. Methods: Propensity score and instrumental variable analyses using a nationwide administrative database, the Japanese Diagnosis Procedure Combination inpatient database, were used. The main outcome was 28-day in-hospital all-cause mortality. Results: Eligible patients (n = 6342) from 936 hospitals were categorized into the rhTM group (n = 1280) or control group (n = 5062). Propensity score matching created a matched cohort of 1140 pairs with and without rhTM. No significant difference in 28-day mortality was documented between the two groups in the unmatched analysis (rhTM vs. control, 37.0%, 474/1280 vs. 36.9%, 1866/5062; odds ratio [OR], 1.00; 95%CI, 0.98-1.03), nor in the propensity-matched analysis (37.6%, 429/1140 vs. 37.0%, 886/1140; OR, 1.01; 95%CI, 0.93-1.10). The logistic regression analysis did not show a significant association between the use of rhTM and 28-day mortality in propensity-matched patients (OR, 1.00; 95%CI, 0.87-1.22). An analysis using the hospital rhTM-prescribing rate as an instrumental variable found that receipt of rhTM was not associated with reduction in mortality at 28 days (risk difference, 0.008; 95% CI, -0.08-0.98). Conclusions: This large retrospective nationwide study demonstrated that there might be little association between the use of rhTM and mortality in severe pneumonia patients with sepsis-associated DIC. A multinational randomized trial is required to confirm this.