title: Association of acquired von Willebrand syndrome with AL amyloidosis.
abstract: Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels.
authors.affiliation: Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Kos
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ward
authors.forename: Karim
authors.initials: K
authors.lastname: Malek
authors.forename: Vaishali
authors.initials: V
authors.lastname: Sanchorawala
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Wright
authors.forename: Carl
authors.initials: C
authors.lastname: O'Hara
authors.forename: Lawreen
authors.initials: L
authors.lastname: Connors
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D000941:Antigens / Q000032:analysis; D001797:Blood Protein Electrophoresis; D004587:Electrophoresis, Agar Gel; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D036102:Peripheral Blood Stem Cell Transplantation; D012074:Remission Induction; D012310:Ristocetin / Q000494:pharmacology; D014182:Transplantation, Autologous; D014842:von Willebrand Diseases / Q000209:etiology* / Q000276:immunology; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D000941:Antigens; D007147:Immunoglobulin Light Chains; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D012310:Ristocetin; D008558:Melphalan