- Paper Report
- Open Access
Antithrombin III and sepsis
- Richard Venn1
© Biomed Central Ltd 2001
- Received: 21 November 2001
- Published: 6 December 2001
- Antithrombin III
Uncontrolled activation of the coagulation system may contribute to the mortality associated with septic shock. This phase III multicentre trial investigated the role of antithrombin III (ATIII), a serine protease inhibitor affecting multiple aspects of the coagulation cascade, in patients with severe sepsis and septic shock.
The baseline ATIII activity was approximately 60% in both groups. This rose to 180% in ATIII group at 24 hours; there was no change in the placebo group at 24 hours.
Overall mortality at 28 days was 38.9% in the ATIII group versus 38.7% in the placebo group; similarly, there was no difference at 90 days.
Statistical evidence for interaction between heparin and ATIII can be derived from multiple logistic regression analysis. There was a significant mortality benefit at 90 days for patients not receiving heparin: 352 (49%) in the ATIII group versus 346 (52.5%) in the placebo group (P = 0.03).
Overall there was no difference between groups except for bleeding events, which had an incidence of 22% in the ATIII group and 13% in the placebo group (P <0.001); this was most marked in patients receiving concomitant heparin therapy.
This was a double-blind, multicentre, phase III, randomised placebo-controlled trial in which 2314 patients with severe sepsis were randomised to receive 30,000 IU ATIII or placebo.
Exclusions included known bleeding disorders, and heparin therapy &151; except low-dose (<10,000 IU/day) subcutaneous heparin or intravenous line flushing with heparin.
- Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke H-O, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM, for the KyberSept Trial Study Group : High-dose antithrombin III in severe sepsis: a randomised controlled trial. JAMA. 2001, 286: 1869-1878.PubMedView ArticleGoogle Scholar