Concomitant acquired and inherited von Willebrand disease: A challenging bleeding disorder

Inherited von Willebrand disease is the most common inherited bleeding disorder and is characterized by mucocutaneous bleeding resulting from impaired platelet adhesion and aggregation at sites of vascular injury. Acquired von Willebrand disease is an often-underrecognized bleeding disorder caused by structural or functional abnormalities of von Willebrand factor secondary to autoimmune, lymphoproliferative, myeloproliferative, plasma cell dyscrasias, malignancy, cardiovascular, or other systemic disorders. The coexistence of inherited and acquired von Willebrand disease should be suspected in patients with a previously stable bleeding phenotype who develop unexplained clinical worsening and requires a high index of clinical suspicion. This scenario presents a significant diagnostic challenge, as laboratory findings may be similar between inherited and acquired forms.

96-year-old woman with known type 2A von Willebrand disease and a previously mild bleeding phenotype who developed worsening bleeding due to acquired von Willebrand disease secondary to previously unrecognized severe aortic stenosis. Genetic sequencing identified a germline variant in exon 28 and an acquired variant in exon 31. Transcatheter aortic valve replacement resulted in rapid improvement of the bleeding phenotype and discontinuation of replacement therapy.

This case underscores the importance of considering acquired von Willebrand disease in patients with inherited von Willebrand disease who present with new-onset or worsening bleeding symptoms, as early recognition enables targeted treatment of the underlying condition and may significantly improve clinical outcomes.