Laboratory testing in hemophilia: Impact of factor and non‐factor replacement therapy on coagulation assays

• Published in: Journal of thrombosis and haemostasis 2020-06, Vol.18 (6), p.1242-1255
• Main Authors: Peyvandi, Flora, Kenet, Gili, Pekrul, Isabell, Pruthi, Rajiv K., Ramge, Peter, Spannagl, Michael
• Format: Article
• Language: English
• Subjects: blood coagulation factors; Clinical Laboratory Techniques; Clotting; Coagulation; Coagulation factors; Diagnosis; emicizumab; factor IX; Factor IX - genetics; Factor IX deficiency; Factor VIII; Hemophilia; hemophilia A; Hemophilia A - diagnosis; Hemophilia A - drug therapy; hemophilia B; Hemophilia B - diagnosis; Hemophilia B - drug therapy; Humans; Laboratories; Monoclonal antibodies; Quality of Life; Thromboplastin
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.14784

The advent of extended half‐life (EHL) recombinant clotting factors and innovative non‐factor replacement therapeutics, such as emicizumab, offers several advantages over existing products for the prophylactic treatment of people living with hemophilia (PwH). These include low annual bleeding rates with less frequent dosing, higher trough plasma concentrations, and a more convenient route of administration. However, increasing use of these therapies poses challenges to clinicians and coagulation laboratories due to the lack of standardized assays for monitoring of hemostatic parameters, and the potential for misinterpretation of test results, which may jeopardize patient safety. Definitive diagnosis of hemophilia and treatment monitoring is reliant on demonstrating factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B) deficiency using a functional coagulation assay. The most frequently used assays are based on activated partial thromboplastin time, using a one‐stage or two‐stage process. While one‐stage and chromogenic assays have performed well with human‐derived FVIII and FIX and full‐length recombinant products, EHL recombinant factors are heterogeneous in structure and mode of action and therefore show wide variation in activity levels between different one‐stage assays, and between one‐stage and chromogenic assays. In the context of the recommended stepwise approach for laboratory diagnosis of hemophilia, we examine the diagnostic challenges associated with the use of EHL factors and novel non‐factor therapeutics and consider the optimal diagnostic approach in PwH who are receiving these treatments. Ultimately, accurate diagnostic solutions are a prerequisite for personalized therapy to minimize treatment burden and improve quality of life in PwH.