Tyr346-->Cys mutation results in factor VIII:C assay discrepancy and a normal bleeding phenotype - is this mild haemophilia A?
Patients with mild haemophilia A may have a discrepancy in the factor VIII (FVIII) level when measured with a one-stage assay (FVIII:C1) compared with a two-stage assay (FVIII:C2). This discrepancy usually results in the one-stage level being higher than the two-stage level. A F8 mutation resulting in a Tyr346-->Cys substitution within the a1 interdomain region has been described which results in the converse assay discrepancy. We report four individuals (three families) who have this mutation. Mean FVIII:C1 level was 25 IU dL(-1) compared with a mean FVIII:C2 level of 63 IU dL(-1). These individuals had presented opportunistically and did not have a clinically significant bleeding disorder. The bleeding phenotype correlated with the two-stage assay result rather than the one-stage result. FVIII replacement therapy does not appear to be required for these individuals.
Lyall
H
H
Department of Haematology, Nottingham University Hospitals NHS Trust, Queens Medical Centre Campus, Nottingham, UK.
Hill
M
M
Westby
J
J
Grimley
C
C
Dolan
G
G
D000328:Adult; D001777:Blood Coagulation / Q000235:genetics; D001780:Blood Coagulation Tests / Q000379:methods / Q000592:standards*; D003951:Diagnostic Errors; D005169:Factor VIII / Q000032:analysis* / Q000235:genetics*; D005192:Family Health; D005260:Female; D006467:Hemophilia A / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D011247:Pregnancy
D005169:Factor VIII