Serial studies in von Willebrand's disease: variability versus "variants"

Area of Science:

• Hematology
• Clinical Pathology
• Genetics

Background:

• Von Willebrand's disease (vWd) is a common inherited bleeding disorder.
• Laboratory findings in vWd can exhibit significant variability.
• Understanding this variability is key for accurate diagnosis and classification.

Purpose of the Study:

• To evaluate the variability of laboratory findings in von Willebrand's disease (vWd).
• To assess the impact of serial testing on diagnosis and classification of vWd.
• To compare variability in patients with vWd to normal individuals.

Main Methods:

• Serial testing of bleeding time (BT), factor VIII coagulant activity (VIII:C), factor-VIII-related antigen (VIIIR:Ag), and ristocetin cofactor (VIIIR:Rcof).
• Study included 50 individuals from 25 families with vWd and 10 healthy controls.
• Characterization of results into 16 possible types based on combinations of four tests.

Main Results:

• Significant variability in BT, VIII:C, VIIIR:Ag, and VIIIR:Rcof observed in individuals with vWd.
• Only homozygous vWd patients consistently showed abnormalities in all four tests.
• Autosomal dominant vWd exhibited diverse results, with all 16 combinations observed; intrafamilial variability was noted.
• Normal individuals showed relative stability, with some variation in factor-VIII-related activities.

Conclusions:

• Laboratory results for vWd tests are highly variable over time in many patients.
• Classifying vWd "variants" based on single sets of tests may be inappropriate.
• Repeated testing is essential for establishing a reliable diagnosis of vWd in some individuals.