Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation

Abstract

ABSTRACT-Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of ATsupplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n ¼ 715, AT group; n ¼ 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n ¼ 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P ¼ 0.034). However, quintile-stratified propensity score analysis (n ¼ 1,784, odds ratio: 0.823 [0.646-1.050], P ¼ 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P ¼ 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P ¼ 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

A summary of the Japan septic disseminated intravascular coagulation study

“…Some experts indicated that an analysis of the survival benefits of AT supplementation therapy over a short period, such as 28 days after ICU admission, yielded more concrete results than that conducted over a long period (the results reported in our previous study21). Therefore, we re‐analyzed the survival benefits of AT supplementation therapy over the 28‐day period after ICU admission.…”

“…Patients were allocated to groups according to treatment with antithrombin (AT group) or without (control group) in the re‐analysis. In the original analysis,21 the observation period was the duration of hospital stay (not restricted). In the re‐analysis, the observation period was restricted to a 28‐day period after ICU admission.…”

“…Therefore, we undertook a nationwide multicenter retrospective observational study, named the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study, which reported the effects of anticoagulant therapy on sepsis in real world clinical settings 18, 19, 20, 21. Herein, we present a summary of the JSEPTIC DIC study.…”

How I treat disseminated intravascular coagulation

“…65 Interestingly, post-hoc subgroup analyses of this study indicated some benefit in patients who did not receive concomitant heparin and in those with the most severe coagulopathy. 66 Recent propensity-adjusted retrospective data from Japan demonstrated a significant advantage of antithrombin-treated patients with severe infection and DIC 67,68 . However these observations require prospective validation.…”

Respiratory extracorporeal membrane oxygenation for severe sepsis and septic shock in adults: a propensity score analysis in a multicenter retrospective observational study

“…The JSEPTIC DIC study included cases of severe sepsis and septic shock,10, 11 as defined at the International Sepsis Definitions Conference 12. Patients younger than 16 years or who had developed severe sepsis or septic shock after ICU admission were excluded.…”