Antithrombin III, first described in 1939 as a cofactor of heparin, is one of the most important physiological inhibitors of coagulation.1 Absence of this cofactor is regarded as incompatible with life, and acquired deficiency—for example, in sepsis—is associated with a high risk of venous thrombosis. In the 1960s researchers found a link between coagulation abnormalities and infection,2 and the anti-inflammatory characteristics of antithrombin III were reported more recently.3 These discoveries have helped us understand how sepsis develops. In the past 15 years, several clinical trials have investigated whether giving antithrombin III to patients who are deficient in this factor—such as those with sepsis, pre-eclampsia, and traumatic brain injury—improves outcomes. Overall, it had no effect on mortality, although it did improve secondary end points in some trials.

In their systematic review in this week’s BMJ, Afshari and colleagues assess the effects of …