Von Willebrand disease type 2M: Correlation between genotype and phenotype

Area of Science:

• Hematology
• Genetics
• Clinical Diagnostics

Background:

• Diagnosing von Willebrand disease (VWD) presents challenges due to variable bleeding patterns and laboratory results.
• Genetic testing offers a powerful tool to aid in the diagnosis and classification of VWD.

Purpose of the Study:

• To investigate the clinical and laboratory characteristics of patients with genetically confirmed VWD type 2M.
• To explore the relationship between genetic variants and patient phenotypes in VWD type 2M.

Main Methods:

• Selection of VWD type 2M patients with genetic variants in the A1 or A3 domains of von Willebrand factor (VWF).
• Analysis of bleeding scores and laboratory results, including VWF activity, VWF antigen, and VWF collagen binding activity.
• Comparison with existing VWD cohort data.

Main Results:

• Fifty patients with VWD type 2M had variants in the A1 domain, exhibiting a median bleeding score of 5.
• These patients showed increased bleeding after surgery/delivery and decreased mucocutaneous bleeding compared to other VWD type 2 cohorts.
• VWF:Act/VWF:Ag ratios were 0.32, and VWF:CB/VWF:Ag ratios were 0.80. Variants in the A3 domain were rare and associated with varied VWF ratios.

Conclusions:

• Genetically confirmed VWD type 2M patients generally present with a mild clinical phenotype, with notable exceptions for bleeding post-surgery or delivery.
• The laboratory phenotype in VWD type 2M is diverse and influenced by specific genetic variations.
• Integrating genetic analysis with current diagnostic methods can enhance the accuracy of VWD diagnosis and classification.