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

J Thromb Haemost. 2015 Jan;13(1):31-40. doi: 10.1111/jth.12786. Epub 2014 Dec 11.

Abstract

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.

Keywords: anticoagulants; disseminated intravascular coagulation; outcomes assessment; pneumonia; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Databases, Factual
  • Disseminated Intravascular Coagulation / diagnosis
  • Disseminated Intravascular Coagulation / drug therapy*
  • Disseminated Intravascular Coagulation / mortality*
  • Female
  • Hospital Mortality
  • Humans
  • Japan / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Pneumonia / mortality*
  • Propensity Score
  • Proportional Hazards Models
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Sepsis / diagnosis
  • Sepsis / mortality*
  • Severity of Illness Index
  • Thrombomodulin / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Recombinant Proteins
  • THBD protein, human
  • Thrombomodulin