Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 6, November-December, p. 1337–1344
Publication type: review article
Acquired von Willebrand Syndrome
1 Department of Hematology and Transplantology, Medical University of Gdańsk, Poland
Acquired von Willebrand syndrome is a rare hemorrhagic diathesis, with clinical symptoms similar to those associated with the inherited form von Willebrand disease. This syndrome is characterized by a lack of previous bleeding symptoms, negative familial history, and occurrence in a relatively older age. Most commonly, acquired von Willebrand syndrome develops in the course of other conditions, such as lymphoproliferative, myeloproliferative, cardiovascular and autoimmune disorders; additionally, it can be associated with some non-hematological malignancies and use of certain prescription drugs. Pathogenesis of von Willebrand syndrome is complex and not fully understood. Deficiency or impaired activity of von Willebrand factor can result from the presence of specific antibodies against this factor, its adsorption onto the surfaces of neoplastic cells, mechanic injury or proteolysis. Diagnosis is based on the measurements of plasma concentration and the activity of von Willebrand factor and multimer analysis. Management of acquired von Willebrand syndrome includes the therapy of the underlying disease and the control or prevention of bleeding. Hemostatic drugs that are most commonly prescribed in this syndrome include desmopressin, von Willebrand factor concentrates, recombinant activated factor VII, intravenous immunoglobulin and adjunctive antifibrinolytic therapy. Additionally, plasmapheresis is required in some cases.
diagnosis, management, prevalence, acquired von Willebrand syndrome
- Collins P, Budde U, Rand JH, Federici AB, Kessler CM: Epidemiology and general guidelines of the management of acquired haemophilia and von Willebrand syndrome. Haemophilia 2008, 3, 49–55.
- Federici AB: Acquired von Willebrand syndrome: An underdiagnosed and misdiagnosed bleeding complication in patients with lymphoproliferative and myeloproliferative disorders. Semin Hematol 2006, 43, 48–58.
- Simone JV, Cornet JA, Abildgaard CF: Acquired von Willebrand’s syndrome in systemic lupus erythematosus. Blood 1968, 31, 806–812.
- Federici AB, Rand JH, Bucciarelli P, Budde U, van Genderen PJ, Mohri H, Meyer D, Rodeghiero F, Sadler JE: Acquired von Willebrand syndrome: Data from an international registry. Thromb Haemost 2000, 84, 345–349.
- Mital A, Prejzner W, Bieniaszewska M, Hellmann A: Prevalence of acquired von Willebrand syndrome during essential thrombocythemia: A retrospective analysis of 170 consecutive patients. Pol Arch Med Wewn 2015, 125, 914–920.
- Mital A, Prejzner W, Hellmann A: Acquired von Willebrand syndrome during the course of myelofibrosis: Analysis of 32 cases. Adv Clin Exp Med 2015, 24, 1001–1006.
- Hanratty JM, Cowan CG: Acquired von Willebrand disease secondary to hypothyroidism: A rare cause for postextraction hemorrhage. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010, 110, 337–340.
- Manfredi E, van Zaane B, Gerdes VE, Brandjes DP, Squizzato A: Hypothyroidism and acquired von Willebrand’s syndrome: A systematic review. Haemophilia 2008, 14, 423–433.
- Meyer AL, Malehsa D, Bara C, Budde U, Slaughter MS, Haverich A, Strueber M: Acquired von Willebrand syndrome in patients with an axial flow left ventricular assist device. Circ Heart Fail 2010, 3, 675–681.
- 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.
- Siaka C, Rugeri L, Caron C, Goudemand J: A new ELISA assay for diagnosis of acquired von Willebrand syndrome. Haemophilia 2003, 9, 303–308.
- Bruggers CS, McElligott K, Rallison ML: Acquired von Willebrand disease in twins with autoimmune hypothyroidism: Response to desmopressin and L-thyroxine therapy. J Pediatr 1994, 125, 911–913.
- Franchini M, de Gironcoli M, Lippi G, Manzato F, Brazzarola P, Bottura D, Aprili G, Gandini G: Efficacy of desmopressin as surgical prophylaxis in patients with acquired von Willebrand disease undergoing thyroid surgery. Haemophilia 2002, 8, 142–144.
- Franchini M, Lippi G: Acquired von Willebrand syndrome: An update. Am J Hematol 2007, 82, 368–375.
- Tefferi A, Nichols WL: Acquired von Willebrand disease: Concise review of occurrence, diagnosis, pathogenesis, and treatment. Am J Med 1997, 103, 536–540.
- Kumar S, Pruthi RK, Nichols WL: Acquired von Willebrand disease. Mayo Clin Proc 2002, 77, 181–187.
- Goudemand J, Samor B, Caron C, Jude B, Gosset D, Mazurier C: Acquired type II von Willebrand’s disease: Demonstration of a complexed inhibitor of the von Willebrand factor-platelet interaction and response to treatment. Br J Haematol 1988, 68, 227–233.
- Mohri H, Motomura S, Kanamori H, Matsuzaki M, Watanabe S, Maruta A, Kodama F, Okubo T: Clinical significance of inhibitors in acquired von Willebrand syndrome. Blood 1998, 91, 3623–3629.
- Van Genderen PJ, Vink T, Michiels JJ, van ‘t Veer MB, Sixma JJ, van Vliet HH: Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen. Blood 1994, 84, 3378–3384.
- Federici AB, Stabile F, Castaman G, Canciani MT, Mannucci PM: Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: Comparison of three different therapeutic approaches. Blood 1998, 92, 2707–2711.
- Richard C, Cuadrado MA, Prieto M, Batlle J, Lopez Fernandez MF, Rodriguez Salazar ML, Bello C, Recio M, Santoro T, Gomez Casares MT: Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells. Am J Hematol 1990, 35, 114–117.
- Scrobohaci ML, Daniel MT, Levy Y, Marolleau JP, Brouet JC: Expression of GpIb on plasma cells in a patient with monoclonal IgG and acquired von Willebrand disease. Br J Haematol 1993, 84, 471–475.
- Budde U, van Genderen PJ: Acquired von Willebrand disease in patients with high platelet counts. Semin Thromb Hemost 1997, 23, 425–431.
- O’Brien JR, Etherington MD: Heart valve stenosis and von Willebrand’s factor multimers. Lancet 1992, 340, 616.
- Strauss RG, Stump DC, Henriksen RA: Hydroxyethyl starch accentuates von Willebrand’s disease. Transfusion 1985, 25, 235–237.
- Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR: Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986, 67, 758–761.
- Pareti FI, Lattuada A, Bressi C, Zanobini M, Sala A, Steffan A, Ruggeri ZM: Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000, 102, 1290–1295.
- Sadler JE: Aortic stenosis, von Willebrand factor, and bleeding. N Engl J Med 2003, 349, 323–325.
- Van Genderen PJ, Prins FJ, Lucas IS, van de Moesdijk D, van Vliet HH, van Strik R, Michiels JJ: Decreased halflife time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: Normalization after cytoreduction of the increased platelet count. Br J Haematol 1997, 99, 832–836.
- Castaman G, Lattuada A, Mannucci PM, Rodeghiero F: Characterization of two cases of acquired transitory von Willebrand syndrome with ciprofloxacin: Evidence for heightened proteolysis of von Willebrand factor. Am J Hematol 1995, 49, 83–86.
- Castaman G, Rodeghiero F, Lattuada A, La Greca G, Mannucci PM: Multimeric pattern of plasma and platelet von Willebrand factor is normal in uremic patients. Am J Hematol 1993, 44, 266–269.
- Federici AB, Berkowitz SD, Lattuada A, Mannucci PM: Degradation of von Willebrand factor in patients with acquired clinical conditions in which there is heightened proteolysis. Blood 1993, 81, 720–725.
- Bracey AW, Wu AH, Aceves J, Chow T, Carlile S, Hoots WK: Platelet dysfunction associated with Wilms tumor and hyaluronic acid. Am J Hematol 1987, 24, 247–257.
- Michiels J, 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, 102–105.
- Tiede A, Rand JH, Budde U, Ganser A, Federici AB: How I treat the acquired von Willebrand syndrome. Blood 2011, 117, 6777–6785.
- Mohri H: Acquired von Willebrand syndrome: Its pathophysiology, laboratory features and management. J Thromb Thrombolysis 2003, 15, 141–149.
- Favaloro EJ, Facey D, Grispo L: Laboratory assessment of von Willebrand factor. Use of different assays can influence the diagnosis of von Willebrand’s disease, dependent on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms. Am J Clin Pathol 1995, 104, 264–271.
- Federici AB, Budde U, Rand JH: Acquired von Willebrand syndrome 2004: International Registry – diagnosis and management from online to bedside. Hamostaseologie 2004, 24, 50–55.
- 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.
- Budde U, Bergmann F, Michiels JJ: Acquired von Willebrand syndrome: experience from 2 years in a single laboratory compared with data from the literature and an international registry. Semin Thromb Hemost 2002, 28, 227–238.
- Budde U, Schneppenheim R, Eikenboom J, Goodeve A, Will K, Drewke E, Castaman G, Rodeghiero F, Federici AB, Batlle J, Perez A, Meyer D, Mazurier C, Goudemand J, Ingerslev J, Habart D, Vorlova Z, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I: Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD). J Thromb Haemost 2008, 6, 762–771.
- Michiels JJ, Budde U, van der Planken M, van Vliet HH, Schroyens W, Berneman Z: Acquired von Willebrand syndromes: Clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Haematol 2001, 14, 401–436.
- Haberichter SL, Castaman G, Budde U, Peake I, Goodeve A, Rodeghiero F, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill FG, Montgomery RR: Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood 2008, 111, 4979–4985.
- Mannucci PM, Lombardi R, Bader R, Horellou MH, Finazzi G, Besana C, Conard J, Samama M: Studies of the pathophysiology of acquired von Willebrand’s disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. Blood 1984, 64, 614–621.
- Sucker C, Michiels JJ, Zotz RB: Causes, etiology and diagnosis of acquired von Willebrand disease: A prospective diagnostic workup to establish the most effective therapeutic strategies. Acta Haematol 2009, 121, 177–182.
- Dalton RG, Dewar MS, Savidge GF, Kernoff PB, Matthews KB, Greaves M, Preston FE: Hypothyroidism as a cause of acquired von Willebrand’s disease. Lancet 1987, 1, 1007–1009.
- Scott JP, Montgomery RR, Tubergen DG, Hays T: Acquired von Willebrand’s disease in association with Wilm’s tumor: Regression following treatment. Blood 1981, 58, 665–669.
- Franchini M, Veneri D, Lippi G: The use of recombinant activated factor VII in congenital and acquired von Willebrand disease. Blood Coagul Fibrinolysis 2006, 17, 615–619.
- Sucker C, Scharf RE, Zotz RB: Use of recombinant factor VIIa in inherited and acquired von Willebrand disease. Clin Appl Thromb Hemost 2009, 15, 27–31.
- Friederich PW, Wever PC, Briet E, Doorenbos CJ, Levi M: Successful treatment with recombinant factor VIIa of therapy-resistant severe bleeding in a patient with acquired von Willebrand disease. Am J Hematol 2001, 66, 292–294.
- Smaradottir A, Bona R: A case of acquired von Willebrand syndrome successfully treated with recombinant Factor VIIa during thyroidectomy. Thromb Haemost 2004, 92, 666–667.
- Delannoy A, Saillez AC: High-dose intravenous gammaglobulin for acquired von Willebrand’s disease. Br J Haematol 1988, 70, 387.
- Federici AB: Use of intravenous immunoglobulin in patients with acquired von Willebrand syndrome. Hum Immunol 2005, 66, 422–430.
- Michiels JJ, van Vliet HH: Acquired von Willebrand disease in monoclonal gammapathies: Effectiveness of highdose intravenous gamma globulin. Clin Appl Thromb Hemost 1999, 5, 152–157.
- Federici AB: Therapeutic approaches to acquired von Willebrand syndrome. Expert Opin Investig Drugs 2000, 9, 347–354.