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.

Keywords:
Acquired von Willebrand disease, Benign monoclonal gammopathy, Immunoglobulin, Systemic lupus erythematosus
1.
Simone JV, Cornet JA, Abildgaard CF: Acquired von Willebrand’s syndrome in systemic lupus erythematosus. Blood 1968;31:806–812.
2.
Michiels JJ, Budde U, van der Planken M, van Vliet HHDM, Schroyens W, Berneman Z: Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Hematol 2001;14:401–436.
3.
Sucker C, Stockschlaeder M, Zotz RB, Scharf RE: Acquired von Willebrand syndrome. Dtsch Med Wochenschr 2004;129:1581–1585.
4.
Van Genderen PJ, Michiels JJ: Acquired von Willebrand disease. Baillieres Clin Haematol 1998;11:319–330.
5.
Federici AB, Rand JH, Bucciarelli P, Budde U, van Genderen PJ, Mohri H, Meyer D, Rodeghiero F, Sadler JE, Subcommittee on von Willebrand Factor: Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 2000;84:345–349.
6.
Kumar S, Pruthi RK, Nichols WL: Estimation of prevalence and natural history of acquired von Willebrand disease (abstract). Haemophilia 2000;6:213.
7.
Mohri H: Acquired von Willebrand syndrome: features and management. Am J Hematol 2006;81:616–623.
8.
Federici AB: Use of intravenous immunoglobulin in patients with acquired von Willebrand syndrome. Hum Immunol 2005;66:422–430.
9.
Franchini M, Lippi G: Acquired von Willebrand syndrome: an update. Am J Hematol 2007;82:368–375.
10.
Michiels JJ, Berneman Z, Gadisseur A, van der Planken M, Schroyens W, Budde U, van Vliet HHDM: Immune-mediated etiology of acquired von Willebrand syndrome in systemic lupus erythematodes and in benign monoclonal gammopathy: therapeuic implications. Semin Thromb Hemost 2006;32:577–588.
11.
Michiels JJ, Schroyens W, Berneman Z, van der Planken M: Atypical variant of acquired von Willebrand syndrome in Wilms tumor: is hyaluronic acid secreted by nephroblastoma cells the cause? Clin Appl Thromb Hemost 2001;7:102–107.
12.
Eikenboom JCJ, Tjernberg P, van Marion V, Heering KJ: Acquired von Willebrand syndrome: diagnostic problems and therapeutic options. Am J Hematol 2007;82:55–58.
13.
Michiels JJ, Berneman Z, Schroyens W, Finazzi G, Budde U, van Vliet HHDM: The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost 2006;32:589–604.
14.
Sadler JE: Aortic stenosis, von Willebrand Factor, and bleeding. N Engl J Med 2003;349:323–325.
15.
Sucker C, Feindt P, Scharf RE: Aortic stenosis, von Willebrand factor, and bleeding. N Engl J Med 2003;349:1773–1774.
16.
Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B: Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003;349:343–349.
17.
Sucker C, Feindt P, Zotz RB, Stockschlaeder M, Scharf RE: Functional von Willebrand factor assays are not predictive for the absence of highest-molecular weight von Willebrand Factor multimers in patients with aortic-valve stenosis. Thromb Haemost 2005;94:465–466.
18.
Scheffold N, Hetzel GR, Cyran J, Sucker C: Heyde’s syndrome – a critical review. Dtsch Med Wochenschr 2006;131:1679–1684.
19.
Sucker C: The Heyde syndrome: proposal for a unifying concept explaining the association of aortic valve stenosis, gastrointestinal angiodysplasia and bleeding. Int J Cardiol 2007;115:77–78.
20.
Rauch R, Budde U, Koch A, Hofbek M: Acquired von Willebrand syndrome in children with patent ductus arteriosus. Heart 2002;88:87–88.
21.
Tiede A, Priesack J, Werwitzke S, Bohlmann K, Oortwijn B, Lenting P, Eisert R, Ganser A, Budde U: Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single-centre cohort study. J Thromb Haemost 2008;6:569–576.
22.
Sucker C, Scharf RE, Zotz RB: Use of recombinant factor VIIa in inherited and acquired von Willebrand disease. Clin Appl Thromb Hemost 2008;15:27–31.
23.
Moll S: Unusual bleeds, unusual clots. Haemostaseologie 2007;27:191–199.
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2009
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