Discrepancies of results for post infusion levels of extended half-life factor VIII/IX concentrates – a cause of concern, awaiting for solution

Hemophilia A and B are X-linked hemorrhagic disorders, characterized by low/dysfunctional factor (F)VIII or FIX, respectively. The history of hemophilia treatment has evolved remarkably over time from the introduction of cryoprecipitate in the 1960s to plasma-derived factors in the 1970s. The 1980s brought a tragic chapter, as many plasma-derived products were contaminated with blood-borne viruses. In response to ongoing safety concerns, recombinant factors were developed in the 1990s. However, coagulation factors had a relatively short half-life upon infusion. As technology progressed, extended half-life factors were introduced in the 2010s. More recently, the development of non-transfusional therapies such as emicizumab has revolutionized prophylaxis. Additionally, gene therapy is emerging as a potentially curative approach. Despite these advances, discrepancies in laboratory assays have emerged as a significant challenge. Treatments employing extended half-life products and/or gene therapy, may yield variable results depending on the type of assays used, typically one-stage clotting vs. chromogenic assays. These discrepancies can lead to confusion in monitoring factor levels and assessing treatment outcome. This article aims to review the current situation on results discrepancies recorded when measuring post infusion extended half-life factors with different methods and to provide guidance on options that may be adopted to minimize discrepancies.