Evaluation of an automated screening assay for von Willebrand disease type 2N

Clin Lab Haematol. 2002 Dec;24(6):369-75. doi: 10.1046/j.1365-2257.2002.00480.x.

Abstract

Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients.

Publication types

  • Evaluation Study

MeSH terms

  • Automation
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay* / instrumentation
  • Factor VIII / metabolism
  • Genes, Recessive
  • Genetic Testing / methods*
  • Genotype
  • Hemophilia A / diagnosis
  • Protein Binding
  • von Willebrand Diseases / classification
  • von Willebrand Diseases / diagnosis*
  • von Willebrand Factor / analysis*
  • von Willebrand Factor / genetics

Substances

  • von Willebrand Factor
  • von Willebrand factor Normandy
  • Factor VIII