Tyr346-->Cys mutation results in factor VIII:C assay discrepancy and a normal bleeding phenotype - is this mild haemophilia A?

Haemophilia. 2008 Jan;14(1):78-80. doi: 10.1111/j.1365-2516.2007.01557.x. Epub 2007 Nov 22.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Blood Coagulation / genetics
  • Blood Coagulation Tests / methods
  • Blood Coagulation Tests / standards*
  • Diagnostic Errors*
  • Factor VIII / analysis*
  • Factor VIII / genetics*
  • Family Health
  • Female
  • Hemophilia A / diagnosis*
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Phenotype
  • Pregnancy

Substances

  • Factor VIII