Acquired von Willebrand syndrome 2004: International Registry

 

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Summary

The acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease. Unlike the congenital form, AVWS usually occurs in individuals with no personal or family history of bleeding. Large studies on AVWS are not available, diagnosis remains difficult and treatment empirical. Acquired von Willebrand syndrome is especially frequent in lympho- or myeloproliferative disorders. It is associated with solid tumours, immunological and cardiovascular disorders as well as other miscellaneous conditions. Diagnosis of AVWS is based on assays measuring ristocetin cofactor activity or collagen binding, which are usually abnormally low, while factor VIII coagulant activity is sometimes within the reference range. FVIII/VWF inhibiting activities are found in only a minority of cases. Bleeding episodes in patients with AVWS are mostly of the mucocutaneous type and can be managed with desmopressin, plasma-derived factor VIII/von Willebrand factor (FVIII/VWF) concentrates and intravenous immunoglobulin. Recombinant activated factor VII can be useful in cases unresponsive to standard therapy. In conclusion, the AVWS, although rare, is certainly underestimated in clinical practice: The actual clinical impact of AVWS should be evaluated by prospective studies. The authors are co-ordinating an updated version of the International Registry on AVWS that will allow data to be entered directly online.

Zusammenfassung

Das erworbene von-Willebrand-Syndrom (VWS) ist eine seltene Erkrankung, die sich laboranalytisch nicht vom angeborenen VWS unterscheiden lässt. Eindeutig different von der angeborenen Form sind das meist deutlich spätere Manifestationsalter sowie die negative Familienanamnese. Größere Studien, die sich mit allen Formen des erworbenen VWS befassen, sind nicht publiziert, die Diagnose ist oftmals schwierig und die Behandlungsmodalitäten sind mehr oder weniger empirisch aufgrund der unbefriedigenden Datenlage. Die Literatur und eine weltweite Umfrage finden die meisten Fälle bei Patienten mit lympho- und myeloproliferativen Erkrankungen. Daneben tritt es noch bei soliden Tumoren und immunologischen Erkrankungen auf, häufiger bei kardiovaskulären Erkrankungen und assoziiert mit einer Reihe anderer, untereinander nicht verwandter klinischer Situationen. Diagnostisch sind erniedrigte funktionelle Parameter des von-Willebrand-Faktors (VWF:RCo und VWF:CB) wegweisend, nicht selten mit normalem oder wenig erniedrigtem VWF:Ag. Häufig liegt die FVIII-Aktivität im Referenzbereich. Die Suche nach Antikörpern gegen den von-Willebrand-Faktor (VWF) ist selten erfolgreich. Die Blutungssymptome ähneln denen von Patienten mit angeborenem VWS. Sie können erfolgreich mit Desmopressin, FVIII/VWF-Konzentraten oder intravenösen Immunglobulinen therapiert werden. Ist hiermit die Situation nicht beherrschbar, bleibt aktivierter rekombinanter FVII. Derzeit ist davon auszugehen, dass das erworbene VWS zwar selten, jedoch eindeutig unterdiagnostiziert ist. Daher sind weitere prospektive Studien notwendig, die sich mit den klinischen Folgen des erworbenen VWS befassen. Die Autoren werden Anfang 2004 eine aktualisierte Fassung des International Registry on AVWS auflegen, das eine direkte Online-Eingabe neu entdeckter Fälle ermöglichen soll.

• References

• 1 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.
  PubMedGoogle Scholar
• 2 Brody JI, Levison SP, Jung CJ. Sickle cell trait and hematuria associated with von Willebrand syndromes. Ann Intern Med 1977; 86: 529-33.
  CrossrefPubMedGoogle Scholar
• 3 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. Sem Thromb Hemost 2002; 28: 227-38.
  Article in Thieme ConnectPubMedGoogle Scholar
• 4 Budde U, Dent JA, Berkowitz SD. et al. Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome. Blood 1986; 68: 1213.
  PubMedGoogle Scholar
• 5 Budde U, Schaefer G, Mueller N. et al. Acquired von Willebrand’s disease in the myeloproliferative syndrome. Blood 1984; 64: 981.
  PubMedGoogle Scholar
• 6 Budde U, van Genderen PJJ. Acquired von Willebrand disease in patients with high platelet counts. Sem Thromb Hemost 1997; 23: 425-31.
  Article in Thieme ConnectPubMedGoogle Scholar
• 7 Cappell MS, Lebwohl O. Cessation of recurrent bleeding from gastrointestinal angiodysplasia after aortic valve replacement. Ann Int Med 1986; 105: 54-7.
  CrossrefPubMedGoogle Scholar
• 8 Carter C, Boughton BJ. Acquired von Willebrand’s disease in myeloproliferative syndrome: spontaneous remission during pregnancy. Thromb Haemost 1992; 67: 387.
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Castaman G, Lattuada A, Mannucci PM. et al. 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.
  CrossrefPubMedGoogle Scholar
• 10 Castaman G, Rodeghiero F. Acquired transitory von Willebrand syndrome with ciprofloxacin. Lancet 1994; 1: 492-3.
  PubMedGoogle Scholar
• 11 Clough V, MacFarlane IA, OConnor J. et al. Acquired von Willebrand’s syndrome and Ehlers-Danlos syndrome presenting with gastrointestinal bleeding. Scand J Haematol 1979; 22: 305-10.
  PubMedGoogle Scholar
• 12 Conrad ME, Latour LF. Acquired von Willebrand’s disease, IgE polyclonal gammopathy and griseofulvin therapy. Am J Hematol 1992; 41: 143.
  PubMedGoogle Scholar
• 13 Coppes MJ, Zandvoort SWH, Sparling CR. et al. Acquired von Willebrand disease in Wilms’ tumor patients. J Clin Onc 1992; 10: 422-7.
  CrossrefPubMedGoogle Scholar
• 14 Dalrymphyle-Hay M, Aitchison R, Collins R. et al. Hydroxyethyl starch induced acquired von Willebrand’s disease. Clin Lab Haematol 1992; 14: 209-11.
  PubMedGoogle Scholar
• 15 Duran-Saurez JR, Pico M, Zuazu J. et al. Acquired von Willebrand’s disease caused by a chronic granulocytic leukemia. Br J Haematol 1981; 48: 173-5.
  CrossrefPubMedGoogle Scholar
• 16 Facon T, Caron C, Courtin P. et al. Acquired type II von Willebrand’s disease associated with adrenal cortical carcinoma. Br J Haematol 1992; 80: 488-94.
  CrossrefPubMedGoogle Scholar
• 17 Federici AB, Rand JH, Bucciarelli P. et al. Acquired von Willebrand Syndrome: data from an International Registry. Thromb Haemost 2000; 84: 345.
  Article in Thieme ConnectPubMedGoogle Scholar
• 18 Federici AB, Rand JH, Mannucci PM. Acquired von Willebrand syndrome: an important bleeding complication to be considered in patients with lymphoproliferative and myeloproliferative disorders. Hematol J 2001; 2: 358-62.
  CrossrefPubMedGoogle Scholar
• 19 Federici AB, Stabile F, Castaman G. et al. Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches. Blood 1998; 92: 2707.
  CrossrefPubMedGoogle Scholar
• 20 Federici AB. Therapeutic approaches to acquired von Willebrand syndrome. Expert Opinion Investigation Drugs 2000; 9: 347.
  PubMedGoogle Scholar
• 21 Friederich PW, Wever PC, Briet E. et al. Successful treatment with recombinant factor VIIa of therapy-resistant severe bleeding in a patient with acquired von Willebrand disease. Am J Hematol 2001; 66: 292-4.
  CrossrefPubMedGoogle Scholar
• 22 Gill JC, Wilson AD, Endres-Brooks J. et al. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986; 67: 758-61.
  PubMedGoogle Scholar
• 23 Holland L, Adamson A, Ingram GI. et al. Acquired von Willebrand’s syndrome. Br J Haematol 1980; 45: 161-4.
  CrossrefPubMedGoogle Scholar
• 24 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 Haematol 1997; 96: 179-82.
  CrossrefPubMedGoogle Scholar
• 25 Ingram GIC, Kingston PJ, Leslie J. et al. Four cases of acquired von Willebrand’s syndrome. Br J Haematol 1971; 21: 184.
  PubMedGoogle Scholar
• 26 Jakway JL. Acquired von Willebrand’s disease. Hematol Oncol Clin North Am 1992; 6: 1409-19.
  CrossrefPubMedGoogle Scholar
• 27 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.
  CrossrefPubMedGoogle Scholar
• 28 Kinoshita S, Yoshioka K, Kasahara M. et al. Acquired von Willebrand disease after Epstein-Barr virus infection. J Pediatr 1991; 119: 595-8.
  CrossrefPubMedGoogle Scholar
• 29 Kreuz W, Linde R, Funk M. et al. Induction of von Willebrand disease type I by valproic acid. Lancet 1990; 335: 1350-1.
  PubMedGoogle Scholar
• 30 Lazarchick J, Green C. Acquired von Willebrand’s disease following bone marrow transplantation. Ann Clin Lab Sci 1994; 24: 211-5.
  PubMedGoogle Scholar
• 31 Mannucci PM, Lombardi R, Bader R. et al. Studies of the pathophysiology of acquired von Willebrand disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. Blood 1984; 64: 614.
  PubMedGoogle Scholar
• 32 Mannucci PM, Remuzzi G, Pusineri F. et al. Deamino-8-D-arginine vasopressin (DDAVP) increases Factor VIII/von Willebrand factor and shortens the bleeding time in uraemia. N Engl J Med 1983; 308: 8-12.
  CrossrefPubMedGoogle Scholar
• 33 McGrath KM, Johnson CA, Stuart JJ. Acquired von Willebrand disease associated with an inhibitor to factor VIII antigen and gastrointestinal telangiectasia. Am J Med 1979; 67: 693-6.
  CrossrefPubMedGoogle Scholar
• 34 Meyer D, Jenkins CSP, Dreyfus M. et al. Willebrand factor and ristocetin. II. Relationship between Willebrand factor, Willebrand antigen and factor VIII activity. Br J Haematol 1974; 28: 579-99.
  CrossrefPubMedGoogle Scholar
• 35 Michiels JJ, Budde U, van der Planken M. et al. Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Practice & Research Clinical Hematology 2001; 14: 401-36.
  PubMedGoogle Scholar
• 36 Mohri H, Motomura S, Kanamori H. et al. Clinical significance of inhibitors in acquired von Willebrand syndrome. Blood 1998; 91: 3623.
  PubMedGoogle Scholar
• 37 Mohri H. Acquired von Willebrand disease in patients with polycythemia rubra vera. Am J Hematol 1987; 26: 135.
  CrossrefPubMedGoogle Scholar
• 38 Murakawa M, Okamura T, Tsutsumi K. et al. Acquired von Willebrand’s disease in association with essential thrombocythemia: regression following treatment. Acta Haematol 1992; 87: 83-7.
  CrossrefPubMedGoogle Scholar
• 39 Nitu-Whalley IC, Lee CA. Acquired von Willebrand syndrome – report of 10 cases and review of the literature. Haemophilia 1999; 5: 318-26.
  CrossrefPubMedGoogle Scholar
• 40 Noronha PA, Hruby MA, Maurer HS. Acquired von Willebrand disease in a patient with Wilms tumor. J Pediatr 1979; 95: 997-9.
  CrossrefPubMedGoogle Scholar
• 41 Nowak-Göttl U, Kehrel B, Budde U. et al. Acquired von Willebrand disease in malignant peripheral neuroectodermal tumor (PNET). Med Pediatr Oncol 1995; 25: 117-8.
  CrossrefPubMedGoogle Scholar
• 42 Pareti FI, Lattuada A, Bressi C. et al. Proteolysis of von Willebrand factor and shear-stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000; 102: 1290-5
  CrossrefPubMedGoogle Scholar
• 43 Pickering NJ, Brody JI, Barrett MJ. Von Willebrand syndromes and mitral-valve prolapse: linked mesenchymal dysplasias. N Engl J Med 1981; 305: 131-4.
  CrossrefPubMedGoogle Scholar
• 44 Raman BKS, Sawdyk M, Saeed M. Essential thrombocythemia with acquired von Willebrand’s disease. Am J Clin Pathol 1987; 88: 102.
  CrossrefPubMedGoogle Scholar
• 45 Rauch R, Budde U, Koch A. et al. Acquired von Willebrand syndrome in children with patent ductus arteriosus. Heart 2002; 88: 87-8.
  CrossrefPubMedGoogle Scholar
• 46 Richard C, Sedano MC, Cuadrado MA. et al. Acquired von Willebrand’s syndrome associated with hydatid disease of the spleen – disappearance after splenectomy. Thromb Haemost 1984; 52: 90-3.
  PubMedGoogle Scholar
• 47 Rinder MR, Richard RE, Rinder HM. Acquired von Willebrand’s disease: A concise review. Am J Hematol 1997; 54: 139.
  CrossrefPubMedGoogle Scholar
• 48 Rogers II JS, Shane SR, Jencks FS. Factor VIII activity and thyroid function. Ann Int Med 1982; 97: 713-6.
  CrossrefPubMedGoogle Scholar
• 49 Scott JP, Montgomery RR, Tubergen DG. et al. Acquired von Willebrand’s disease in association with Wilm’s tumor: regression following treatment. Blood 1981; 58: 665-9.
  PubMedGoogle Scholar
• 50 Simone JV, Cornet JA, Abildgaard CF. Acquired von Willebrand’s syndrome in systemic lupus erythematosus. Blood 1968; 31: 806.
  PubMedGoogle Scholar
• 51 Stableforth P, Tamagnini GL, Dormandy KM. Acquired von Willebrand syndrome with inhibitors both to factor VIII clotting activity and ristocetin-induced platelet aggregation. Br J Haematol 1976; 33: 565-73.
  CrossrefPubMedGoogle Scholar
• 52 Strauss RG, Stump DC, Henriksen RA. Hydroxyethyl starch accentuates von Willebrand’s disease. Transfusion 1985; 25: 235-7.
  CrossrefPubMedGoogle Scholar
• 53 Tatewaki W, Takahashi H, Hanano M. et al. Multimeric composition of plasma von Willebrand factor in chronic myelocytic leukaemia. Thromb Res 1988; 52: 23.
  CrossrefPubMedGoogle Scholar
• 54 Tefferi A, Nichols WL. Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis and treatment. Am J Med 1997; 103: 536.
  CrossrefPubMedGoogle Scholar
• 55 Tran TC, Mannucci PM, Schneider P. et al. Profound alterations of the multimeric structure of von Willebrand factor in a patient with malignant lymphoma. Br J Haematol 1985; 61: 307-14.
  CrossrefPubMedGoogle Scholar
• 56 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.
  Article in Thieme ConnectPubMedGoogle Scholar
• 57 van Genderen PJJ, Leenknegt H, Michiels JJ. et al. Acquired von Willebrand disease in myeloproliferative disorders. Leukemia and Lymphoma 1996; 22: 79.
  PubMedGoogle Scholar
• 58 van Genderen PJJ, Michiels JJ, van der Poelvan de Luytgaarde SC. et al. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: relationship with platelet count. Ann Hematol 1994; 69: 81.
  CrossrefPubMedGoogle Scholar
• 59 Veyradier A, Jenkins CS, Fressinaud E. et al. Acquired von Willebrand syndrome: from pathophysiology to management. Thromb Haemost 2000; 84: 175.
  Article in Thieme ConnectPubMedGoogle Scholar
• 60 Vincentelli A, Susen S, Le Tourneau T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003; 349: 343-9.
  CrossrefPubMedGoogle Scholar
• 61 Weinstein M, Ware JA, Troll JH. et al. Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. Blood 1988; 71: 1648-55.
  PubMedGoogle Scholar
• 62 Yoshida H, Arai K, Wakashin M. Development of acquired von Willebrand’s disease after mixed connective tissue disease. Am J Med 1988; 85: 445-6.
  PubMedGoogle Scholar