Acquired von Willebrand Syndrome – Pathophysiology

The pathophysiology of acquired von Willebrand syndrome (AvWS). Different mechanisms are implicated depending on the underlying cause/disease. 1) In patients with hypothyroidism, the syndrome is caused by the decreased synthesis of an otherwise qualitatively normal won Willebrand factor (vWF). 2) In patients with plasma cell dyscrasias (for example, monoclonal gammopathy of undetermined significance [MGUS] and multiple myeloma), and in those with autoimmune diseases such as systemic lupus erythematosus, circulating autoantibodies are directed against functional or non-functional vWF domains. Antibody binding to vWF results in the formation of immune complexes that are cleared from the circulation by the reticulo-endothelial system. Rarely, antibodies neutralize platelet-related vWF activities. 3) In patients with certain types of cancer, including myeloproliferative neoplasms, high-molecular-weight (HMW) multimers are or selectively adsorbed on tumor cells or platelets, leading to increased plasma clearance. 4) In patients with abnormal heart valves (shown schematically as interrupted black line) or those being treated with left ventricular assist devices, mechanical stress promotes the sheering of HMW vWF multimers or proteolysis induced by ADAMTS13.Learn more here.