Summary. 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 ¼ 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P ¼ 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 ¼ 0.6; 9.8% vs. 3.1% for patients without DIC, P ¼ 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 highdose AT treatment.

Background: For patients with a normal coagulation system, who experience serious bleeding, sound evidence for recombinant activated factor VII (rFVIIa) as an effective haemostatic agent is only scarcely available so far from controlled clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment failures were only rarely reported.

None of the new drugs, however, has successfully become established as a new standard of care. In the future, studies of novel sepsis therapies may succeed better if suitable biomarkers allow for patient selection, reflecting key pathophysiologic mechanisms that are targeted by the innovative drugs.