Laboratory Testing of Inhibitors

THSNA Highlights Issues in Accurate Laboratory Testing of Inhibitors

THSNA 2016 (Chicago, April 14-16): Factor replacement can be complicated by the development of antibodies that block or neutralize the activity of replacement factor, so called “inhibitors”.  Two poster presentations at the Thrombosis and Hemostasis Summit of North America (THSNA) highlight specific issues around accurate and consistent testing for inhibitors, which are a more common problem for young children with hemophilia A than B. In the first poster, Drs. Adcock and Miller reviewed the literature on methods for factor inhibitor measurement with the objective to propose an evidence-based standard method of factor inhibitor measurement in North America. Data showed methodological variation, namely small differences in how laboratories run the “same” test, resulted in high variability between laboratories, with up to 32% rate of diagnosing an inhibitor when there isn’t one (false positive) and 5% rate of missing an inhibitor when there is one (false negative). From these results, a standard procedure for inhibitor measurement will be presented for submission to two professional societies representing laboratories (NASCOLA) and hematologists working in bleeding disorders (HTRS). In another poster, the Centers for Disease Control and Prevention (CDC) presented their data on very specific modifications of the standard Nijmegen-Bethesda Assay to identify low titer inhibitors. While standard assays can identify a titer as low as 0.6 Bethesda Units (BUs), CDC’s assays could go down to a lower limit of detection of 0.2 NBU.  Further, using antibodies to factor VIII that fluoresce (glow under lights), called fluorescence immunoassay (FLI) they could detect even lower inhibitor titers.