Acquired von Willebrand syndrome and mitral valve prosthesis leakage. A pilot study Almudena Pe ´ rez-Rodrı ´guez 1 , Joana Costa Pinto 1 , Esther Loure ´s 1 ,A ´ ngela Rodrı ´guez-Trillo 1 , Jose ´ J. Cuenca 2 , Javier Batlle 1,3 , Marı ´a F. Lo ´ pez-Ferna ´ ndez 1 1 Servicio de Hematologı ´a y Hemoterapia, INIBIC-Complexo Hospitalario Universitario A Corun ˜ a, A Corun ˜ a; 2 Servicio de Cirugı ´a Cardı ´aca, Complexo Hospitalario Universitario A Corun ˜ a, A Corun ˜ a; 3 Department of Medicine, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with clinical laboratory findings similar to those of inherited von Willebrand disease (VWD) (1). AVWS causes impaired primary hemostasis with pro- longed bleeding time and reduced platelet adhesion. In contrast to congenital VWD, patients with AVWS typi- cally show late onset of bleeding events with no personal or family history (2). AVWS is usually caused by auto- immune clearance or inhibition of VWF, increased shear-induced proteolysis of VWF, increased binding of VWF to platelets or other cell surfaces, and reduced VWF synthesis associated with hypothyreosis or antiepi- leptic treatment with valproic acid (3). Inherited VWD is common (4, 5), while AVWS is a rare disorder with an estimated prevalence of 0.04% (6), which is probably underestimated (7, 8). An international registry for AVWS recently established by Federici et al. (2) shows that AVWS is especially frequent in lympho- or myeloproliferative (63%) and cardiovascular diseases (21%). In the latter group, AVWS was reported to be associated with some cases of aortic stenosis (4%), angiodysplasia (2%), atrial defects (1%), mitral prolapse (1%), and several other defects (13%). Recent similar cases have been found in patients having ventricular assist devices (VADs) (9, 10). In preparation for surgery for these cases, therapeutic interventions are restricted to Abstract Background: Of patients with severe aortic stenosis, 15–25% present with bleeding episodes possibly attributable to acquired von Willebrand syndrome (AVWS). AVWS associated with mitral valve prosthesis leakage has not been reported. Methods and Results: Five patients receiving appropriate oral anticoagula- tion showed mitral valve prosthesis leakage and bleeding episodes; all of them required hospitalization and two blood transfusions, and a von Willebrand factor (VWF) analysis was performed. Two patients with nor- mal functioning metallic prosthesis valves were included as controls. Before surgery, after cessation of acenocumarol, the patients had prolonged activated partial thromboplastin time; four had prolonged closure time (CT) from the platelet function analyzer. Factor VIII procoagulant activity (FVIII:C), VWF ristocetin co- factor activity (VWF:RCo), and VWF collagen binding (VWF:CB) were considerably elevated, while VWF antigen (VWF:Ag) was most elevated. Disproportionate VWF:RCo ⁄ VWF:Ag and VWF:CB ⁄ VWF:Ag ratios were seen with the loss of large VWF multimers. Following surgery, all parameters were markedly increased and the ratios, CT, and multimeric VWF profile became normal. Conclusions: Acquired VWF qualitative alterations in mitral valve prosthesis leakage may be associated with or contribute to bleeding diathesis. AVWS should be taken into consideration in patients with mitral valve prosthesis leakage with bleeding diathesis not explained by excessive oral anticoagulation. Key words acquired von Willebrand syndrome; mitral valve prosthesis; von Willebrand factor; bleeding diathesis; surgery Correspondence Francisco Javier Batlle Fonrodona, MD, Servicio de Hematologı ´a y Hemoterapia, Complexo Hospitalario Universitar- io A Corun ˜ a (Edificio Hospital Materno Infantil), Carretera del Pasaje s ⁄ n, 15006 - A Corun ˜ a, Spain. Tel: 34 981 178000 (Extensio ´n 292113); Fax: 34 981 178392; e-mail: francisco.javier.batlle.fonrodona@sergas.es Accepted for publication 6 June 2011 doi:10.1111/j.1600-0609.2011.01664.x ORIGINAL ARTICLE European Journal of Haematology 87 (448–456) 448 ª 2011 John Wiley & Sons A/S