Gene therapy for hemophilias: the end of phenotypic testing or the start of a new era?

: Hemophilia comprises two distinct genetic disorders caused by missing or defective clotting factor VIII (hemophilia A) or clotting factor IX (hemophilia B). The management of these conditions has been for long based on replacement therapies, but emerging evidence garnered from recent landmark studies suggests that a promising avenue toward routine use of gene therapy is clearly progressing forward, thus generating unavoidable consequences on laboratory hemostasis, especially as pertaining to phenotypic testing. Although it seems likely that widespread use of gene therapy will be associated with a relative decrease of hemostasis tests requests in this patient population due to the relatively stable effect of transgene delivery and persistent production of endogenous clotting factor, some important aspects persuade us that conventional laboratory diagnostics, especially encompassing activated partial thromboplastin time, as well as one-stage and two-stage clotting factor assays, will not be completely voided in the gene therapy era. In particular, phenotypic testing will remain essential for excluding acquired or sporadic cases of hemophilia, for identifying and titrating factor inhibitors, as well as for defining and monitoring the long-term therapeutic effectiveness of gene transfection in hemophiliacs.