title: Causes, etiology and diagnosis of acquired von Willebrand disease: a prospective diagnostic workup to establish the most effective therapeutic strategies.
abstract: Acquired von Willebrand disease (aVWD) occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative and myeloproliferative disorders, other malignancies, and cardiovascular disease. aVWD is a complex and heterogeneous defect with a multifactorial etiology and the pathophysiologic mechanisms remain unclear in many cases. Assays for anti-factor VIII (FVIII)/von Willebrand factor (VWF) activities often yield negative results although antibodies may be present in autoimmune disease and some lymphoproliferative disorders. Functional assays of VWF in patients' plasma and particularly in heart valve disease, VWF multimer analysis are important for aVWD diagnosis. In patients with normal partial thromboplastin times and normal VWF activity, the diagnosis of aVWD is based on clinical suspicion and a careful bleeding history, which should prompt the clinician to initiate further laboratory investigations. Management of bleeding in aVWD relies mainly on desmopressin, FVIII/VWF concentrates and high-dose intravenous immunoglobulin. The half-life of VWF may be very short, and in bleeding episodes high doses of FVIII/VWF concentrates at short intervals may be necessary even when high-dose intravenous immunoglobulin was applied before. Since the optimal treatment strategy has not yet been defined for aVWD of different etiology, controlled multicenter trials aiming at the development of standardized treatment protocols are urgently needed.
authors.affiliation: LaboMed Coagulation Center Berlin, Tauentzienstrasse 7 b/c, Berlin, Germany. sucker@labomed.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Sucker
authors.forename: Jan Jacques
authors.initials: JJ
authors.lastname: Michiels
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Zotz
mesh_terms: D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D006331:Heart Diseases / Q000150:complications; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000276:immunology; D009369:Neoplasms / Q000150:complications / Q000276:immunology; D014842:von Willebrand Diseases / Q000139:chemically induced / Q000145:classification / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D014841:von Willebrand Factor / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D014841:von Willebrand Factor; D003894:Deamino Arginine Vasopressin