Abstract Number: PB1587
Meeting: ISTH 2020 Congress
Background: Type 2N Von Willebrand Disease (VWD) is characterised by a decreased capacity of Von Willebrand Factor (VWF) to bind Factor VIII (FVIII) 1. The differential diagnosis to exclude mild Haemophilia A includes calculation of FVIII:VWF ratio, assessment of the FVIII binding capacity of VWF, and analysis of the VWF gene. Classification is essential for appropriate treatment and genetic counselling.
Aims: The aim of the study was to investigate the relationship between phenotype and genotype for patients with suspected Type 2N VWD.
Methods: VWF:FVIIIB assesses the ability of plasma VWF at a standard concentration (0.10 IU/ml) to bind recombinant FVIII (rFVIII) using an ELISA assay3. Results are expressed as percent VWF:FVIIIB by correlation with a standard curve. Analysis was performed on plasma from 31 patients. Patients were genotyped for the common VWF variant associated with 2N VWD (p.R854Q) 2.
Results: A local VWF:FVIIIB reference interval was established previously (74-97%). 16/31 patient results were within this reference interval; median FVIII:VWF Ag ratio 0.68 and VWF p.R854Q absent on genotyping. Remaining patient results (15/31) were subdivided into two categories based on the local reference interval and kit manufacturers recommendations (patients with VWF:FVIIIB capacity of < /= 20% are considered to have Type 2N VWD). 4/15 patient results were within the range of 20-74% VWF:FVIIIB; median FVIII:VWF Ag ratio 0.72 and VWF p.R854Q heterozygous on genotyping. 11/15 patient results were less than 20% VWF:FVIIIB; median FVIII:VWF Ag ratio 0.38. Of these; eight were homozygous for VWF p.R854Q, one compound heterozygous for VWF p.R854Q and two heterozygous for VWF p.R854Q with an additional likely null variant (not further analysed).
Conclusions: This study demonstrates a relationship between phenotype and genotype for patients with suspected Type 2N VWD. A reduction in VWF:FVIIIB is predictive of the presence of VWF p.R854Q. Furthermore < 20% VWF:FVIIIB is suggestive of homozygosity for VWF p.R854Q.
To cite this abstract in AMA style:Doyle M, Keenan C, Mullaney B, Byrne M, Ryan K, O Donnell JS, Ahmed S, O Connell NM. Measurement of VWF:FVIII Binding (VWF:FVIIIB) in a Cohort of Patients with Suspected Type 2N VWD and Correlation with Genetic Analysis of the VWF Gene [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/measurement-of-vwffviii-binding-vwffviiib-in-a-cohort-of-patients-with-suspected-type-2n-vwd-and-correlation-with-genetic-analysis-of-the-vwf-gene/. Accessed November 29, 2023.
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