Acquired von Willebrand syndrome: A case series of nine patients and literature review

Purpose. - Whereas von Willebrand disease is the most common constitutional bleeding disorder, acquired von Willebrand syndrome is rare. Methods. - Retrospective, monocentric descriptive study of consecutive cases of acquired von Willebrand syndrome diagnosed between 2000 and 2012. Diagnostic criteria included: absence of a past history of mucocutaneous bleeding, with low plasma levels of factor VIII (FVIII) and von Willebrand factor (VWF), ristocetine cofactor activity (RCo) and antigen (Ag). Results. - Nine men were diagnosed with von Willebrand syndrome. Six of them presented with recent mucocutaneous bleeding. In eight cases, the biological phenotype was a type 2 von Willebrand disease, with decreased VWF:RCo/VWF:Ag ratio. A lymphoproliferative disease with circulating paraprotein was identified in all patients, including one chronic lymphoid leukemia, three Waldenstrom and one marginal zone lymphomas, four monoclonal gammapathies of unknown significance. Screening for an anti-VWF inhibitor was negative. Symptomatic treatment using infusion of VWF concentrates was administrated in the presence of severe mucocutaneaous bleeding. Five patients received intravenous immunoglobulins with a good response only in patients with G isotype paraprotein. A chemotherapy was initiated if indicated for the underlying disorder. Three of the four patients who achieved remission of the associated lymphoma had a subsequent improvement of plasma VWF levels, while all other patients remained deficient. Conclusion. - Acquired von Willebrand syndrome is a rare but potentially serious disease. The diagnostic should be suspected in adults with unusual mucocutaneous bleeding, with or without prolonged partial thromboplastin time (PIT), and confirmed with a decreased plasma level of VWF (Ag and RCo). An associated haematological, neoplastic or cardiac valvular disease must be searched. (C) 2013 Societe nationale francaise de medecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.