Fibrin sealant: current and potential clinical applications.

There are few well-controlled studies of the clinical efficacy of fibrin sealant, defined by lives saved or reduced need for blood transfusions. Evaluation of fibrin sealant in trauma situations, e.g. liver laceration, has been difficult to perform. Only recently has fibrin sealant been actively promoted by US manufacturers as a commercially valuable alternative to the relatively inexpensive crude bovine thrombin and cryoprecipitate that are in current use. Regulatory agencies and manufacturers are aware that patients in the USA are receiving a suboptimal form of fibrin glue since cryoprecipitate is not virally inactivated and has a variable fibrinogen concentration. In addition, bovine thrombin is not regulated with respect to factor V content or any other impurities. During the past year regulatory agencies, together with manufacturers and clinicians, have begun to define clinically valid endpoints for efficacy of a commercially prepared fibrin sealant. These may include improvement in hemostasis compared with a placebo or agents considered to be 'standard of care'. Thus, the regulatory agencies may be willing to consider studies in animals that demonstrate efficacy as well as surrogate endpoints, such as reduced factor concentrate requirements in patients with severe hemophilia requiring dental extraction. As fibrin sealant becomes available in a liquid and potentially in a bandage form, it may also become an essential matrix for recombinant factors that can affect endothelial function.