Acquired von Willebrand disease: from theory to practice. A single center experience - three case reports

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Acquired von Willebrand disease (AvWD) represents a rare, potentially severe and most likely underdiagnosed category of hemorrhagic syndromes determined by quantitative, qualitative or functional, nonhereditary, alterations of von Willebrand factor (vWF) that occur in the context of various underlying diseases. It is diagnosed mainly in adults, without any personal or familial history of bleeding. The etiopathogeny of AvWD is complex, marked by the intervention of multiple mechanisms, occuring in the evolution of neoplasia, autoimmune disorders, cardiovascular diseases and other conditions. The clinical and laboratory manifestations are similar to the congenital form with mucocutaneous hemorrhage in patients without bleeding history and demonstration of quantitative and/or functional anomalies of vWF. Treatment has two major objectives: control of bleeding and therapy of the underlying condition. As a practical illustration of the theoretical aspects we present 3 clinical cases of AvWD diagnosed in the Colţea Hospital Department of Hematology during the last 10 years.

1. Shetty S, Kasatkar P, Ghosh K. Pathophysiology of acquired von Willebrand disease: a concise review. Eur J Haematol 2011; 87(2):99–106. DOI: 10.1111/j.1600-0609.2011.01636.x

2. Franchini M, Lippi G. Acquired von Willebrand syndrome: an update. Am J Hematol. 2007;82(5):368–75. DOI: 10.1002/ajh.20830

3. Mohri H. Acquired von Willebrand syndrome: Its pathophysiology, laboratory features and management. J Thromb Thrombolysis. 2003;15(3):141–9. DOI: 10.1023/B:THRO.0000011369.70824.e6

4. Mohri H. Acquired von Willebrand syndrome: features and management. Am J Hematol. 2006;81(8):616-23. DOI: 10.1002/ajh.20455

5. Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood. 2011;117(25):6777-85. DOI: 10.1182/blood-2010-11-297580

6. Federici AB, Rand JH, Bucciarelli P, Budde U, Van Genderen PJJ, Mohri H, et al. Acquired von Willebrand syndrome: data from an International registry. Thromb Haemost. 2000;84(2):345-9.

7. Tiede A. Diagnosis and treatment of acquired von Willebrand syndrome. Thrombosis Research. 2012;130(Suppl. 2):S2–S6. DOI: 10.1016/S0049-3848(13)70003-3

8. Federici AB. Budde U, Castaman G, Rand HR, Tiede A. Current diagnostic and therapeutic approaches to patients with acquired von Willebrand syndrome: a 2013 update. Semin Thromb Hemost. 2013;39(2):191-201. DOI: 10.1055/s-0033-1334867

9. Boissier E, Darnige L, Dougados J, Arlet JB, Dupeux S, Georgin-Lavialle S, et al. Acquired von Willebrand syndrome: A case series of nine patients and literature review. Rev Med Interne. 2014;35(3):154-9. DOI: 10.1016/j.revmed.2013.02.039

10. 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(2):227-38. DOI: 10.1055/s-2002-27824

11. Federici AB, Budde U, Rand JH. Acquired von Willebrand syndrome 2004: International registry. Hamostaseologie. 2004;24(1):50–5.

12. Federici AB. Acquired von Willebrand syndrome: an underdiagnosed and misdiagnosed bleeding complication in patients with lymphoproliferative and myeloproliferative disorders. Semin Hematol 2006;43(1 Suppl 1):S48–58. DOI: 10.1053/j.seminhematol.2005.11.003

13. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003;349(4):343-9. DOI: 10.1056/NEJMoa022831

14. Fukumoto Y. Impact of acquired von Willebrand syndrome in severe aortic stenosis. J Atheroscler Thromb. 2015;22(11):1113-4. DOI: 10.5551/jat.ED024

15. Tamura T, Horiuchi H, Imai M, Tada T, Shiomi H, Kuroda M, et al. Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index. J Atheroscler Thromb. 2015 Nov 2;22(11):1115-23. DOI: 10.5551/jat.30809

16. Zoghi B, Shaughnessy P, Lyons RM, Helmer R, Bachier C, LeMaistre CF. Treatment of Acquired von Willebrand Syndrome and Prevention of Bleeding Postautologous Stem Cell Transplant during Severe Pancytopenia with IVIG. Case Rep Hematol. 2015;2015:809313. DOI: 10.1155/2015/809313

17. Franchini M, Castaman G, Coppola A, Santoro C, Zanon E, Di Minno G, et al. Acquired inhibitors of clotting factors: AICE recommendations for diagnosis and management. Blood Transfus. 2015;13(3):498-513.

18. Lancelloti S, Dragani A, Ranalli P, Petrucci G, Basso M, Tartaglione R, et al. Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count. J Thromb Haemost. 2015;13(7):1226-37. DOI: 10.1111/jth.12967

19. 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(3):471–5. DOI: 10.1111/j.1365-2141.1993.tb03103.x

20. 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(11):1290–5. DOI: 10.1161/01.CIR.102.11.1290

21. Kruse-Jarres R. Acquired bleeding disorders in the elderly. Hematology Am Soc Hematol Educ Program. 2015. 2015(1):231-6. DOI: 10.1182/asheducation-2015.1.231

22. Pipe N, Goldenberg N. Acquired Disorders of Hemostasis. In Orkin SH, Fisher DE, Ginsburg D, Look TA, Lux SE, Nathan DG Eds. Nathan and Oski’s Hematology and Oncology of Infancy and Childhood 8th Ed. Elsevier Saunders, Philadelphia. 2015:1103-24.

23. Tiede A, Priesack J, Werwitzke S, Bohlmann K, Oortwijn B, Lenting P, et al. Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single centre cohort study. J Thromb Haemost. 2008;6(4):569-76. DOI: 10.1111/j.1538-7836.2008.02909.x

24. Manfredi E, van Zaane B, Gerdes V.E.A, Brandjes D.P.M, Squizzato A. Hypothyroidism and acquired von Willebrand’s syndrome: a systematic review. Haemophilia. 2008;14(3):423-33. DOI: 10.1111/j.1365-2516.2007.01642.x

25. Stuijver DJ, Piantanida E, van Zaane B, Galli L, Romualdi E, Tanda ML, et al. Acquired von Willebrand syndrome in patients with overt hypothyroidism: a prospective cohort study. Haemophilia. 2014;20(3):326-32. DOI: 10.1111/hae.12275

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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