Controversial efficacy of antithrombin followed by recombinant thrombomodulin administration in patients with sepsis-induced disseminated intravascular coagulation: an analysis of postmarketing surveillance data.

BACKGROUND

Anticoagulant therapy is considered useful for sepsis patients with disseminated intravascular coagulation (DIC); however, the efficacy of combination therapy with anticoagulants is still under investigation.

METHODS

We evaluated anticoagulant use in 1,770 patients with sepsis-induced DIC from 314 institutions by analyzing postmarketing survey data on plasma-derived antithrombin (AT) concentrates. DIC was defined as a DIC score above 4 according to the Japanese Association for Acute Medicine (JAAM). We divided patients into quartiles according to JAAM-defined DIC and Sequential Organ Failure Assessment (SOFA) scores to determine the efficacy of concomitant recombinant thrombomodulin (rTM) following AT supplementation, and we performed a propensity score-adjusted analysis.

RESULTS

The 28-day mortality rate after AT administration was 24.1%. We categorized patients on the basis of a JAAM-defined DIC score of 6 and a SOFA score of 9, because the patients' median JAAM-defined DIC and SOFA scores were 5 and 9, respectively. Among patients with JAAM-defined DIC scores >6 and SOFA scores >9, patients treated with AT followed by rTM (concomitant rTM use) had a significantly lower mortality rate (28.5%) than did those treated without concomitant rTM (40.0%) (p = 0.031). However, among patients with JAAM-defined DIC scores of four or five, the patients treated with concomitant rTM had a significantly greater mortality rate than did those not treated with concomitant rTM, irrespective of whether their SOFA score was below or above 9 (18.5% vs. 10.1%, p = 0.036 and 37.0% vs. 24.3%, p = 0.018, respectively). The incidence of serious bleeding- related adverse events did not differ between patients with and without concomitant rTM treatment.

CONCLUSIONS

efficacy of rTM administration following AT supplementation in patients with sepsis-induced DIC is controversial, and the evidence is restricted to decreasing mortality rates in patients with JAAM-defined DIC scores >6 and SOFA scores>9. However, further studies are needed to confirm these findings.