Administration of recombinant thrombomodulin before progression of disease causing disseminated intravascular coagulation might be better compared with administration after progression of disease

Abstract

Background: As disseminated intravascular coagulation (DIC) causes multiple organ failure, recombinant thrombomodulin (rTM) is widely used in Japan for treating DIC. However, the optimal timing of rTM administration has not yet been determined. We hypothesized that the administration of rTM before progression of disease causing DIC might be better for the treatment of DIC than that after progression of disease. Methods: A total of 101 patients received rTM in the intensive care unit (ICU) between August 2008 and November 2013 were enrolled. Depending on survival at hospital discharge, the patients were divided into survivor (group S) and non-survivor groups (group NS). Patient characteristics before DIC development, acute physiology and chronic health evaluation II (APACHEII) score and sequential organ failure assessment (SOFA) score at the start of rTM administration, rTM administration dose, duration of time between the onset of disease causing DIC and rTM administration, and combination therapy were collected. Results: Group S had 57 patients, and group NS had 44 patients. More than 70% of patients in group S were administrated rTM within 1 day from the onset of disease causing DIC (0 days, 40% vs 20%; 1 day, 33% vs 30%; more than 2 days, 26% vs 50%). At the start of the rTM administration, the APACHEII and SOFA scores were significantly lower in group S (26 ± 6 vs 32 ± 6, p < 0. 001; 9.5 ± 4.2 vs 13.4 ± 3.6, p < 0.001). Multivariate logistic regression analysis of outcomes was performed. The duration of time between the onset of disease causing DIC and rTM administration, the APACHEII score, the SOFA score, and use of continuous renal replacement therapy (CRRT) were selected as candidate variables (p < 0.05). The SOFA scores and use of CRRT were highly correlated with the APACHEII score (Pearson correlation = 0.63 and 0.43, respectively). Therefore, the SOFA score and the use of CRRT were excluded from this model. Late administration of rTM (more than 2 days between the onset of disease and rTM administration) was associated with undesirable outcome (odds ratio = 3.36, 95% confidence interval = 1.03-10.92, p = 0.044).Conclusions: This study suggested that the administration of rTM before the progression of disease causing DIC might be better than that after progression of disease causing DIC. Further randomized clinical trials are required to elucidate whether early administration of rTM is actually effective.