Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

J Thromb Haemost. 2006 Jan;4(1):90-7. doi: 10.1111/j.1538-7836.2005.01697.x.

Abstract

Background: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality.

Objectives: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC.

Patients and methods: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination.

Results: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02).

Conclusions: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antithrombin III / adverse effects
  • Antithrombin III / therapeutic use*
  • Disseminated Intravascular Coagulation / drug therapy*
  • Disseminated Intravascular Coagulation / etiology
  • Disseminated Intravascular Coagulation / mortality
  • Double-Blind Method
  • Ethnic Groups
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Sepsis / mortality
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antithrombin III