In vitro evaluation of factor VIII--bypassing activity of activated prothrombin complex concentrate, prothrombin complex concentrate, and factor VIIa in the plasma of patients with factor VIII inhibitors: thrombin generation test in the presence of collagen-activated platelets.

Clinical efficacy of plasma-derived products with factor VIII--bypassing activity in patients with factor VIII inhibitors is difficult to evaluate. It is also difficult to predict efficacy by coagulation assay. A test of thrombin generation in defibrinated plasma and in the presence of activated platelets was used to test the bypassing activity of the most currently used products (activated prothrombin complex concentrate from various origins, prothrombin complex concentrate, and factor VIIa). The bypassing activity was evaluated in the absence and presence of tissue factor. In plasma with inhibitor, activated prothrombin complex concentrate elicited dose-dependent thrombin formation, whereas prothrombin complex concentrate and factor VIIa induced only minimal thrombin activity. Addition of tissue factor in the assay elicited thrombin generation in the presence of factor VIIa and prothrombin complex concentrate and allowed additional thrombin formation in the presence of activated prothrombin complex concentrate. Although it is hazardous to extend results of in vitro testing to clinical efficacy, our study sheds some light on the mechanism of action of the various substances used to treat bleeding episodes in patients with factor VIII inhibitors.