Acquired von Willebrand Disease in Monoclonal Gammapathies: Effectiveness of High-dose Intravenous Gamma Globulin

Abstract

The reported underlying lymphoproliferative dis orders associated with acquired von Willebrand disease (AvWD) include benign monoclonal gammapathy, multiple myeloma, Waldenström disease, chronic lymphocytic leuke mia, non-Hodgkin lymphoma, and hairy cell leukemia. The AvWD in patients with a monoclonal gammapathy and/or a lymphoproliferative disorder is featured by a prolonged bleed ing time, normal platelet count, and a decreased or absent ris tocetine-induced platelet aggregation in combination with a prolonged aPTT and normal PT due to low levels of factor VIII/von Willebrand factor (vWF) parameters in the absence of a factor VIII inhibitor in the Bethesda assay. In vitro and vivo experiments consistently showed that the anti-vWF autoanti bodies in monoclonal gammapathies cause a rapid clearance of the factor VIII/vWF complex from the circulation after DDAVP and factor VIII/vWF concentrate infusion. Multimeric analysis of the vWF usually show a type 11-like AvWD due to the absence of large vWF multimers as the consequence of the rapid clearance of the anti-vWF-factor VIII/vWF complex from the circulation. There is a poor response to intravenous DDAVP and factor VIII/vWF concentrate infusion, but high dose intravenous gamma globulin (1 g/kg for 2 days) usually induces a transient correction of the factor VIII/vWF param eters for 1 to a few weeks.