Acquired von Willebrand Syndrome Hiding Inherited von Willebrand Disease Can Explain Severe Bleeding in Patients With Aortic Stenosis.

Abstract

Aortic stenosis may be complicated by an acquired von Willebrand syndrome that rarely causes significant bleeding, raising the question of why it does so in a few cases. To seek an explanation, we studied 5 severe bleeder aortic stenosis patients in a cohort of 49 patients, using the flowchart for inherited von Willebrand disease. Approach and Results: All 5 patients were lacking in large and intermediate VWF (von Willebrand factor) multimers, 3 had reduced plasma and platelet VWF levels, and none showed PFA100 closure. Two patients (those with most multimers missing) also had a short VWF half-life. Genetic analyses on the 3 patients with reduced platelet VWF levels revealed that one carried both the c.1164C>G and the c.7880G>A mutations, and another carried the c.3390C>T mutation, while the third had one of the 2 VWF alleles relatively less expressed than the other (25% versus 75%). No genetic alterations emerged in the other 2 patients. Successful replacement of the stenotic aortic valve, performed in the 2 patients with VWF mutations, did not correct their abnormal VWF multimer picture-unlike what happened in the aortic stenosis patients without bleeding symptoms. Our findings suggest that acquired von Willebrand syndrome can develop in patients with hitherto-undiagnosed inherited von Willebrand disease. Since von Willebrand disease is the most common bleeding disorder, this possibility should be considered in aortic stenosis patients-especially those with a more severe bleeding history and more disrupted VWF laboratory patterns-because they risk hemorrhage during aortic valve replacement.