Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a secondary survey

Toshiaki Iba, Daizoh Saitoh, Hideo Wada, Hidesaku Asakura

IntroductionIn a previous report, we demonstrated a favorable trend for supplementation with antithrombin (AT) concentrate at a dosage of 3000 IU/day over 1500 IU/day for the treatment of sepsis-associated disseminated intravascular coagulation (DIC) in patients with an AT activity of 70% or less. Since the survival difference did not reach statistical significance, we planned to examine the effects in a larger number of cases with severer disease.MethodsWe performed a nonrandomized multi-institutional survey. A total of 307 septic DIC patients with AT activity less than 40% and who had undergone AT substitution at a dose of either 1500 IU/day or 3000 IU/day for three consecutive days were analyzed. Of these, 259 patients received 1500 IU/day (AT1500 group) and 48 patients received 3000 IU/day (AT3000 group). The primary efficacy endpoints were recovery from DIC by day 7 and an all-cause mortality on day 28. Adverse bleeding events were also examined. A logistic regression analysis was conducted using age, sex, body weight, initial AT activity, DIC score, platelet count, coadministration of heparin, recombinant thrombomodulin, suspected source of infection, surgery, and supplemented AT dose.ResultsSupplementation significantly decreased the DIC score in the AT3000 group, leading to the superior resolution of DIC, compared with the results in the AT1500 group (66.7% versus 45.2%, P = 0.007). In addition, the AT3000 group exhibited a better survival than the AT1500 group (77.1% versus 56.4%, P = 0.010). Bleeding events were observed in 6.96% (severe bleeding: 3.04%) in AT1500 group and 6.52% (severe bleeding, 4.35%) in AT3000 group (P = 1.000 (severe bleeding, P = 0.648)). A logistic regression analysis revealed that the use of AT3000 (odds ratio (OR), 2.419; P = 0.025), a higher initial platelet count (OR, 1.054; P = 0.027), and patient age (OR, 0.977; P = 0.045) were significantly correlated with an improved survival.ConclusionThe AT3000 group exhibited significantly improved rates of survival and recovery from DIC without an increased risk of bleeding, compared with the AT1500 group, among the patients with sepsis-associated DIC and an AT activity <40%.