Clinical impact of recombinant thrombomodulin administration on disseminated intravascular coagulation due to severe acute cholangitis (Recover-AC study).

BACKGROUND AND AIM Recombinant thrombomodulin (rhTM) is potentially effective in the treatment of disseminated intravascular coagulation (DIC). Several studies related to drugs for the treatment of acute cholangitis have shown negative results in improvement of overall survival (OS) with rhTM. The aim of this multicenter study was to evaluate the clinical effectiveness of rhTM in patients with acute cholangitis and sepsis-induced DIC who underwent biliary drainage. METHODS Consecutive 284 patients, who were complicated with sepsis-induced DIC due to severe acute cholangitis, were included (rhTM group, n=173; non-rhTM, n=111) in this study. The primary outcome was the DIC resolution rate at 7 days after starting treatment. The 28-day survival rate was secondarily evaluated. RESULTS DIC scores in the rhTM group improved significantly compared with the non-rhTM group on day 7 (P=0.020). According to multivariate analysis, etiology of cholangitis (malignant, HR 2.28), rhTM (non-administration, HR 4.13), and DIC score (≥5, HR 2.46) were significant factors associated with failed DIC resolution on day 7. Propensity score matching created 103 matched pairs. Survival rate at day 28 was significantly higher in rhTM group (94.3%) compared with non-rhTM group (82.6%) (P=0.048) after propensity score matching. rhTM (non-administration, HR 2.870), DIC score (≥5, HR 2.751), and APACHE II score (≥20, HR 9.310) were significant factors associated with decreasing survival rate at day 28. CONCLUSION In conclusion, rhTM seemed to improve patient survival, but future studies should only include patients with benign or malignant disease and should be performed according to APACHE II scores.