Specific Factor Inhibitor Testing

Inhibitors may occur in congenitally deficient patients who fail to respond as expected to appropriate therapy (alloantibodies) or in previously unaffected patients (autoantibodies). They are detected in the laboratory primarily through their ability to neutralize specific coagulation factors and must be distinguished from nonspecific inhibitors, such as the lupus anticoagulant. Most commonly, an inhibitor is detected by performing a specific coagulation factor assay on a mixture of patient plasma and normal pool plasma and comparing the result to a control mixture. Factor VIII (FVIII) inhibitor testing has been standardized as the Bethesda assay; other factor inhibitors are tested in an analogous way. FVIII inhibitors and some inhibitors to factors V and XI are time-dependent and require incubation; others usually react immediately. Bethesda assays detect only antibodies that neutralize the clotting factor in the fluid phase, whereas nonneutralizing antibodies may be detected by other methods, such as enzyme-linked immunosorbent assay.