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Ferrata Storti Foundation
Haematologica 2020 Volume 105(8):2032-2037
Acquired von Willebrand syndrome: focused for hematologists
Massimo Franchini1 and Pier Mannuccio Mannucci2
1Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantua and 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
ABSTRACT
The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike the inherited disease, AvWS occurs in persons with no personal and family history of bleeding and is often associated with a variety of underlying diseases, most frequently lymphoproliferative, myeloproliferative and cardiovascular disorders. After the presentation of a typical case, in this narrative review we discuss the more recent data on the pathophysiology, clinical, laboratory and therapeutic aspects of this acquired bleeding syndrome. We chose to focus particularly on those aspects of greater interest for the hematologist.
Introduction
Acquired von Willebrand syndrome (AvWS) is a rare but probably underestimat- ed bleeding disorder characterized by laboratory findings and clinical presentations similar to those of inherited von Willebrand disease (vWD).1-8 Differing from vWD, a bleeding disorder due to quantitative or qualitative genetic defects of von Willebrand factor (vWF),9,10 AvWS usually occurs more frequently in adults with no personal or family history for a bleeding diathesis. Although it was first recognized more than 50 years ago (it was described in 1968 in a patient with systemic lupus erythematosus), AvWS has gained renewed interest in the last few years due to its association with relatively frequent cardiovascular disorders, including congenital heart defects, aortic stenosis, and the use of left ventricular assist devices.11-15 In addition to these, many other underlying diseases are associated with AvWS, rang- ing from solid and hematologic cancers to autoimmune diseases.16-18 Various mech- anisms are implied in the pathophysiology of AvWS, the majority of them leading to the increased degradation or clearance of circulating vWF. This article reviews current knowledge on the mechanisms, diagnostic, clinical and therapeutic aspects of AvWS, focusing particularly on those cases associated with hematologic disor- ders. AvWS associated with cardiovascular diseases is not discussed here because it requires particular diagnostic and treatments strategies which were extensively and recently analyzed.11-15,19,20 A brief description of an individual case provides an example which allows us to introduce the main characteristics and management of the syndrome.
Clinical case
A 70-year old man presented to the emergency room of the main Mantua city hospital in north east Italy with spontaneous gingival bleeding. Apart from mild fatigue and headache, the patient felt well, with no bruising or other hemorrhagic symptoms. His medical history was positive for hypertension under satisfactory drug control but negative for a bleeding diathesis, and he had undergone an inguinal herniotomy 20 years earlier with no hemorrhagic complications. On phys- ical examination, there was mild cutaneous and conjunctival pallor, blood oozing from the gums, and lymphadenomegaly at superficial stations (maximum diame- ter, 2 cm). Blood tests revealed normocytic anemia (hemoglobin 9 g/dL), with nor- mal white cell and platelet counts. With a normal prothrombin time, the activated partial thromboplastin time (APTT) was mildly prolonged (ratio, 1.29; normal range, 0.82-1.18), but its full correction with a normal plasma mixing test excluded
Correspondence:
PIER MANNUCCIO MANNUCCI
piermannuccio.mannucci@policlinico.mi.it
Received: April 14, 2020. Accepted: May 27, 2020. Pre-published: June 18, 2020.
doi:10.3324/haematol.2020.255117
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/8/2032
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