Factor VIII Inhibitor

Factor VIII inhibitors are IgG antibodies that are directed against coagulation factor VIII (FVIII). They may occur in alloimmunized patients with congenital FVIII deficiency (Hemophilia A) or as autoantibodies (acquired FVIII inhibitors). The latter may be associated with malignancy, pregnancy, autoimmune disease, or drugs, but most often occur spontaneously, particularly among elderly persons.

Acquired inhibitors to FVIII will prolong the Activated Partial Thromboplastin time (APTT). Typically, this prolonged clotting time will be corrected on addition of an equal amount of normal plasma. Thus, it is possible for such an inhibitor to be missed on a simple mixing study, where the APTT is run immediately after mixing the patient and normal sample together.  However, the inhibitory activity will become evident if the mixture of patient and normal plasma is incubated at 37oC for a period of 2 hours. In the Florida Hospital Center for Thrombosis Research, all mixing studies include this incubation step.

FVIII inhibitors can be confirmed and quantitated using a specific Bethesda assay. In this test, the patient's plasma is mixed with a known quantity of FVIII.  After a 2 hour incubation period at 37°C, the residual FVIII activity is determined in a specific FVIII clotting assay. By comparing the difference in the FVIII activity of the patient incubation mixture and the original control, the absence or presence of a FVIII inhibitor can be demonstrated. If positive, the results are reported in Bethesda Units (BU).