Recombinant Thrombomodulin in Disseminated Intravascular Coagulation Associated with Stage IV Solid Tumors: A Nationwide Observational Study in Japan

Abstract Objective The terminal stage of solid tumors sometimes induces disseminated intravascular coagulation (DIC); however, no useful therapeutic strategies have been established. This study investigated the relationship between mortality and recombinant human soluble thrombomodulin (rTM) therapy for patients with DIC associated with stage IV solid tumors using a large nationwide inpatient database. Methods Using the Japanese Diagnosis Procedure Combination Inpatient Database, patients with stage IV solid tumors who developed DIC were identified. Those who received rTM within 3 days of admission were included in the treatment group; the remaining were included in the control group. The primary outcome was the 28-day in-hospital mortality. Results Of 25,299 eligible patients, 1 to 4 propensity score matching was used to select 1,979 rTM users and 7,916 nonusers. There was no significant difference in the 28-day mortality (control vs. rTM: 37.4% vs. 34.3%; hazard ratio, 0.95; 95% confidence interval [CI], 0.88–1.04) and critical bleeding rate (control vs. rTM: 3.7% vs. 3.8%; odds ratio, 1.04; 95% CI, 0.75–1.42) between groups. Subgroup analyses showed that the 28-day mortality rate among patients with colorectal and gynecological cancer was significantly lower in the rTM than in the control group (p for interaction 0.033 and 0.010, respectively). Conclusion Although we identified a possibly beneficial association between rTM administration and mortality in specific populations of patients with colorectal and gynecological cancer, no such association was found when considering the entire cohort of patients with DIC associated with stage IV solid tumors.