Download PDF
Thromb Haemost 2000; 84(02): 345-349
DOI: 10.1055/s-0037-1614018
Scientific and Standardization Committee Communication
Schattauer GmbH

Acquired von Willebrand Syndrome: Data from an International Registry

On behalf of the Subcommittee on von Willebrand Factor
Augusto B. Federici
1   From Angelo Bianchi Bonomi Hemophilia Thrombosis Center, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Italy
,
Jacob H. Rand
2   Hematology Division Mount Sinai School of Medicine, New York, USA
,
Paolo Bucciarelli
1   From Angelo Bianchi Bonomi Hemophilia Thrombosis Center, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Italy
,
Ulrich Budde
3   Coagulation Laboratory, Hamburg, Germany
,
Perry J. J. van Genderen
4   Department of Hematology, University Hospital, Rotterdam, The Netherlands
,
Hiroshi Mohri
5   Yokohama City University, 1st Dept of Internal Medicine, Yokohama, Japan
,
Dominique Meyer
6   Hopital de Bicetre, Paris, France
,
Francesco Rodeghiero
7   Hemophilia and Thrombosis Center, Department of Hematology, Vicenza, Italy
,
Evan J. Sadler
8   Howard Hughes Medical Institutions, Washington University, St. Louis, USA
› Author Affiliations
Further Information

Publication History

Received 06 March 2000

Accepted after revision 27 April 2000

Publication Date:
14 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of congenital von Willebrand disease (vWD). Despite the numerous cases reported in the literature until 1999 (n = 266), large studies on AvWS are not available. Moreover, diagnosis of AvWS has been difficult and treatment empirical. These considerations prompted us to organize an international registry. A questionnaire, devised to collect specific information on AvWS, was sent to all the members of the International Society on Thrombosis and Haemostasis (ISTH), who were invited to respond if they had diagnosed cases with the AvWS cases. 156 members answered the questionnaire and 54 of them sent information on 211 AvWS cases from 50 centers. Data were compared with those already published in the literature and 25 cases already described or not correctly diagnosed were excluded. The 186 AvWS cases that qualified for the registry were associated with lymphoproliferative (48%) and myeloproliferative disorders (15%), neoplasia (5%), immunological (2%), cardiovascular (21%) and miscellaneous disorders (9%). Ristocetin cofactor activity (vWF:RCo) or collagen binding activity (vWF:CBA) were usually low in AvWS (median values 20 U/dL, range 3-150), while factor VIII coagulant activity was sometimes normal (median 25 U/dL, range 3-191). FVIII/vWF inhibiting activities were present in only a minority of cases (16%). Bleeding episodes in AvWS were mostly of mucocutaneous type (68%) and were managed by DDAVP (32%), FVIII/vWF concentrates (37%), intravenous immunoglobulins (33%), plasmapheresis (19%), corticosteroids (19%) and immunosuppressive or chemotherapic agents (35%). Based upon the data of this international registry, it appears that AvWS is especially frequent in lympho-or myeloproliferative and cardiovascular diseases. Therefore, AvWS should be suspected and searched with the appropriate laboratory tests especially when excessive bleeding occurs in patients with these disorders. On the basis of the information provided by this registry guidelines for diagnosis and management of the AvWS are given.

Keywords

Acquired von Willebrand syndrome - diagnosis - therapy
 

  • References

  • 1 Simone JV, Cornet JA, Abildgaard CF. Acquired von Willebrand’s syndrome in systemic lupus erythematosus. Blood 1968; 31: 806-12.
    PubMedSearch in Google Scholar
  • 2 Mannucci PM, Mari D. Antibodies to factor VIII/von Willebrand factor in congenital and acquired von Willebrand’s disease. Prog Clin Biol Res 1984; 150: 109-22.
    PubMedSearch in Google Scholar
  • 3 Glaspy JA. Hemostatic abnormalities in multiple myeloma and related disorders. Hemat /Oncol Clinics N Amer 1992; 06: 1301-14.
    PubMedSearch in Google Scholar
  • 4 Jakway JL. Acquired von Willebrand’s disease in malignancy. Sem Thromb Hemost 1992; 18: 434-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Jakway JL. Acquired von Willebrand’s disease. Hematol Oncol Clin North Am 1992; 06: 1409-19.
    CrossrefPubMedSearch in Google Scholar
  • 6 Rinder MR, Richard RE, Rinder HM. Acquired von Willebrand’s disease: a concise review. Am J Hematol 1997; 54: 139-45.
    CrossrefPubMedSearch in Google Scholar
  • 7 Tefferi A, Nichols WL. Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis and treatment. Am J Med 1997; 103: 536-40.
    CrossrefPubMedSearch in Google Scholar
  • 8 van Genderen PJJ, Michiels JJ. Acquired von Willebrand disease. Ballière’s Clinical Haematology 1998; 03: 319-30.
    PubMedSearch in Google Scholar
  • 9 Nitu-Whalley IC, Lee CA. Acquired von Willebrand syndrome – report of 10 cases and review of the literature. Haemophilia 1999; 05: 318-26.
    CrossrefPubMedSearch in Google Scholar
  • 10 Dalton RG, Dewar MS, Savidge GF, Kernoff PBA, Matthews KB, Greaves M, Preston FE. Hypothyroidism as a cause of acquired von Willebrand’s disease. Lancet 1987; 01: 1007-9.
    PubMedSearch in Google Scholar
  • 11 Mannucci PM, Lombardi R, Bader R, Horellou MH, Finazzi G, Besana C, Conard J, Samama M. Studies of the pathophysiology of acquired von Willebrand disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. Blood 1984; 64: 614-21.
    PubMedSearch in Google Scholar
  • 12 Noronha PA, Hruby MA, Maurer HS. Acquired von Willebrand disease in a patient with Wilms tumor. J Pediatr 1979; 95: 997-9.
    CrossrefPubMedSearch in Google Scholar
  • 13 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: 665-9.
    PubMedSearch in Google Scholar
  • 14 Richard C, Sedano MC, Cuadrado MA, Recio M, Hermosa V, Zubizarreta A. Acquired von Willebrand’s syndrome associated with hydatid disease of the spleen-disappearance after splenectomy. Thromb Haemost 1984; 52: 90-3.
    PubMedSearch in Google Scholar
  • 15 Cappell MS, Lebwohl O. Cessation of recurrent bleeding from gastrointestinal angiodysplasia after aortic valve replacement. Ann Int Med 1986; 105: 54-7.
    CrossrefPubMedSearch in Google Scholar
  • 16 Weinstein M, Ware JA, Troll JH, Salzman EW. Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. Blood 1988; 71: 1648-55.
    PubMedSearch in Google Scholar
  • 17 Coppes MJ, Zandvoort SWH, Sparling CR, Poon AO, Weitzman S, Blanchette VS. Acquired von Willebrand disease in Wilms’ tumor patients. J Clin Onc 1992; 10: 422-7.
    CrossrefPubMedSearch in Google Scholar
  • 18 Facon T, Caron C, Courtin P, Wurtz A, Deghaye M, Bauters F, Mazurier C, Goudemand J. Acquired type II von Willebrand’s disease associated with adrenal cortical carcinoma. Br J Haematol 1992; 80: 488-94.
    CrossrefPubMedSearch in Google Scholar
  • 19 Anderson RP, McGrath K, Street A. Reversal of aortic stenosis, bleeding gastrointestinal angiodysplasia, and von Willebrand syndrome by aortic valve replacement. Lancet 1996; 347: 689-90.
    PubMedSearch in Google Scholar
  • 20 Duran-Saurez JR, Pico M, Zuazu J, Cortes M, Monasterio J, Tringiner J. Acquired von Willebrand’s disease caused by a chronic granulocytic leukemia. Br J Haematol 1981; 48: 173-5.
    CrossrefPubMedSearch in Google Scholar
  • 21 Tran TC, Mannucci PM, Schneider P, Federici AB, Bachmann F. Profound alterations of the multimeric structure of von Willebrand factor in a patient with malignant lymphoma. Br J Haematol 1985; 61: 307-14.
    CrossrefPubMedSearch in Google Scholar
  • 22 Murakawa M, Okamura T, Tsutsumi K, Kamura T, Shibuya T, Harada M, Niho Y. Acquired von Willebrand’s disease in association with essential thrombocythemia: regression following treatment. Acta Haematol 1992; 87: 83-7.
    CrossrefPubMedSearch in Google Scholar
  • 23 Budde U, van Genderen PJJ. Acquired von Willebrand disease in patients with high platelet counts. Sem Thromb Hemost 1997; 23: 425-31.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Joist JH, Cowan JF, Zimmerman TS. Acquired von Willebrand’s disease: evidence for a quantitative and qualitative factor VIII disorder. N Engl J Med 1978; 298: 988-91.
    CrossrefPubMedSearch in Google Scholar
  • 25 Dalrymphyle-Hay M, Aitchison R, Collins R, Sekhar M, Colvin B. Hydroxy-ethyl starch induced acquired von Willebrand’s disease. Clin Lab Haematol 1992; 14: 209-11.
    PubMedSearch in Google Scholar
  • 26 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: 83-6.
    CrossrefPubMedSearch in Google Scholar
  • 27 Inbal A, Bank I, Zivelin A. Acquired von Willebrand disease in a patient with angiodysplasia resulting from immune-mediated clearance of von Willebrand factor. Br J Haemat 1997; 96: 179-82.
    CrossrefPubMedSearch in Google Scholar
  • 28 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: 2707-11.
    PubMedSearch in Google Scholar
  • 29 Scott JP, Vokac EA, Schroeder T. et al. The von Willebrand factor (vWF) propolypeptide, von Willebrand factor antigen II, distinguishes von Willebrand syndrome (AvWS) due to the decreased synthesis of vWF from AvWS due to increased clearance of vWF. [Abstract] Blood 1995; 86: 196a.
    PubMedSearch in Google Scholar
  • 30 van Genderen PJJ, Boertjes RC, van Mourik JA. Quantitative analysis of von Willebrand factor and its propeptide in plasma in acquired von Willebrand syndrome. Thromb Haemost 1998; 80: 495-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 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: 3623-9.
    CrossrefPubMedSearch in Google Scholar