External quality assessment of factor VIII inhibitor assays

Inhibitors to coagulation factors cause prolongation of routine hemostasis laboratory test results and have clinical relevance in the management of congenital and acquired hemophilia patients. Factor VIII (FVIII) inhibitors can be either allo-antibodies (in hemophilia A) or auto-antibodies (in acquired hemophilia) directed against FVIII. The most commonly used assays for detecting these inhibitors are the classical Bethesda assay or a modified (Nijmegen) method. Previous laboratory assessments from the Royal College of Pathologists of Australia Quality Assurance Program (RCPAQAP) Haematology and other external quality assessment programs have shown wide variability in FVIII inhibitor results and method performance, as well as a significant degree of false-positive and false-negative interpretations. Despite its limitations, the Bethesda assay is still the primary assay used in laboratories for detecting the presence and strength of a FVIII inhibitor. Therefore, it is of utmost importance that this assay is performed well. The current report reviews the most recent findings from the RCPAQAP Haematology, which show there is still a need for better standardization and improvement in the detection of low-level FVIII inhibitors to ultimately provide better clinical management of affected patients.