Experience with antithrombin concentrates in neurotrauma patients

Plasma coagulation results from 2,100 injured patients were sequentially and systematically evaluated in a large natural history study of neurotrauma. A significant correlation became apparent between the severity of and morbidity from head injury and the degree of abnormality in coagulation results, especially for young injured victims. Subsequent studies in the United States, Europe, and Japan have supported the significant correlation between final clinical outcome and these measurements of plasma coagulation, as well as inflammatory proteins, performed soon after injury. This discussion reviews the data from many published reports that support this conclusion, especially data that corroborate the strong clinical association between head trauma and disseminated intravascular coagulation (DIC). The data that demonstrate a high predisposition for head-injured individuals to develop DIC serve as a the rationale for therapeutic intervention with coagulation protease inhibitors, especially antithrombin (AT). A large, double-blind, placebo-controlled trial that evaluates the therapeutic use of AT concentrate for DIC in such patients has yet to be completed. Described here is the design for such a clinical trial that examined the impact of mortality as an outcome. However, this trial was terminated for nonscientific reasons soon after it began. Very truncated data collected from this aborted study support both the scientific rationale for and the feasibility of such a study in the future. Data from such a clinical trial are needed to support the use of AT concentrate to treat DIC in this and other morbid diseases.