Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling

Br J Haematol. 1990 Nov;76(3):372-9. doi: 10.1111/j.1365-2141.1990.tb06371.x.

Abstract

A plasma von Willebrand factor (vWf) defect limited to its failure to bind factor VIII (FVIII) was previously characterized in a woman with FVIII deficiency and normal primary haemostasis. By using in vitro tests we found a similar pattern in three siblings of another family previously thought to be affected with mild haemophilia A. Furthermore, a decrease in vWf ability to bind FVIII was found in the parents and the brother of the three patients. This decrease was consistent with heterozygous expression of a recessive vWf gene abnormality. FVIII deficiency was corrected by infusion with a vWf concentrate almost devoid of FVIII coagulant activity. FVIII recovery and half-life thus obtained showed that this treatment was more effective than a FVIII infusion performed by way of comparison. These results indicate that this vWf defect may account for FVIII deficiency in patients without the usual laboratory and clinical features of von Willebrand's disease. Changes in therapy and genetic counselling following the new diagnosis in this family emphasize the need to search for such a vWf defect in patients in whom FVIII deficiency is not obviously X-linked.

MeSH terms

  • Child
  • Child, Preschool
  • Diagnostic Errors
  • Factor VIII / metabolism*
  • Female
  • Genetic Counseling
  • Genetic Variation
  • Hemophilia A / diagnosis*
  • Hemorrhagic Disorders / diagnosis*
  • Hemorrhagic Disorders / drug therapy
  • Hemorrhagic Disorders / genetics
  • Heterozygote
  • Humans
  • Male
  • Pedigree
  • von Willebrand Factor / genetics*
  • von Willebrand Factor / metabolism
  • von Willebrand Factor / therapeutic use

Substances

  • von Willebrand Factor
  • Factor VIII