B-domain deleted extended half-life factor VIII concentrates have come to be the chosen hemophilia A therapies, along with emicizumab [HemLibra®], approved in 2017. Coagulation laboratories can no longer rely upon the time-honored one-stage clot-based factor assay to accurately report BDD EHL therapeutic factor VIII activity, nor can these tests be used to monitor patient factor levels during emicizumab therapy, as emicizumab normalizes the PT and PTT. Coagulation labs are switching to the two-stage chromogenic factor VIII assays that employ a bovine factor X substrate. The bovine substrate is necessary as emicizumab does not interfere with the reaction. Click here for a poster that describes the analytica characteristics of Precision BioLogic's CRYOcheck® Chromogenic Factor VIII on three different automated coagulation analyzers.
In addition to the need for a more accurate and reproducible activity assay, several manufacturers are developing quantitative [antigenic] assays that return valid BDD factor VIII results. See the Affinity Biologicals poster, Improved Recognition of B-Domain Deleted FVIII in Plasma with a New Commercially Available VisuLize™ F8Plus Antigen Kit.