The diagnosis of HA is established by assaying plasma F8 activity. Given that F8 normally relies on binding to VWF for survival, all patients with a low F8 activity should be excluded for a diagnosis of Von Willebrand disease (VWD). In addition, F8 is a labile factor resulting in a loss of up to 15% F8 activity in suboptimally processed plasma specimens. Thus, mild reductions in F8 activity should prompt repeat testing with careful attention to specimen handling. While a reduced F8 activity in at-risk females typically confirms carrier status, a normal F8 activity does not exclude carrier status. In such cases, molecular genetic testing is the only option for diagnosis.
Knowledge of the causative F8 mutation in probands does not alter clinical management but may be useful in predicting the risk of developing F8 inhibitors.4 Mutation identification also is useful for focusing on the relevant region of the F8 gene in carrier testing of family members. Rarely, adopted asymptomatic females with no access to their familial F8 genotype will need their entire F8 gene analyzed for carrier testing. For carriers, prenatal diagnosis during pregnancy provides useful information for management of labor and delivery and, occasionally, pregnancy termination. Advances in reproductive technology may permit preimplantation genetic diagnosis and circumvent the need for prenatal testing.5
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