A Rare Combination of von Willebrand Disease Type 2A and 2M: Diagnostic and Therapeutic Challenges - A case report.

BACKGROUND

Combined von Willebrand disease (VWD) type 2A/2M is a rare phenotype characterized by overlapping qualitative defects affecting both multimer structure and von Willebrand factor (VWF) function.

KEY CLINICAL QUESTION: How can congenital VWD be distinguished from acquired von Willebrand syndrome (AVWS) when both conditions contribute to an abnormal laboratory phenotype?

CLINICAL APPROACH: A 73-year-old man with a previous diagnosis of VWD type 2M presented with severe gastrointestinal bleeding and severe aortic stenosis. Repeat VWF analysis showed loss of high-molecular-weight multimers, consistent with AVWS secondary to shear stress. Treatment with recombinant VWF (Veyvondi) restored high-molecular-weight multimers and achieved hemostatic control. Following transcatheter aortic valve implantation, the abnormal multimer pattern persisted. Subsequent genetic testing identified a pathogenic VWF variant, p.Leu1446Pro, confirming congenital VWD type 2A/2M.

CONCLUSION

This case demonstrates how AVWS may obscure an underlying congenital VWD phenotype. Combined phenotypic and molecular diagnostics are essential for accurate classification, therapeutic decision making, and interpretation of complex VWD phenotypes.