Download PDF
Thromb Haemost 2014; 112(03): 427-431
DOI: 10.1160/TH13-11-0952
Review Article
Schattauer GmbH

Gastrointestinal angiodysplasia and bleeding in von Willebrand disease

Massimo Franchini
1   Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantova, Italy
,
Pier Mannuccio Mannucci
2   Scientific Direction, IRCCS Cà Granda Foundation Maggiore Hospital, Milan, Italy
› Author Affiliations
Further Information

Publication History

Received: 19 November 2013

Accepted after minor revision: 08 April 2014

Publication Date:
20 November 2017 (online)

    Permissions and Reprints

Summary

Von Willebrand disease (VWD), the most common genetic bleeding disorder, is characterised by a quantitative or qualitative defect of von Willebrand factor (VWF). Patients with VWD suffer from mucocutaneous bleeding, of severity usually proportional to the degree of VWF defect. In particular, gastrointestinal bleeding associated with angiodysplasia is often a severe symptom of difficult management. This review focuses on the pathophysiology, diagnosis and treatment of VWD-associated gastrointestinal angiodysplasia and related bleeding.

Keywords

von Willebrand disease - bleeding - gastrointestinal angiodysplasia - therapy
 

  • References

  • 1 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987; 69: 454-459.
    PubMedGoogle Scholar
  • 2 Sadler JE, Budde U, Eikenboom JC. et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 04: 2103-2114.
    CrossrefPubMedGoogle Scholar
  • 3 Mannucci PM. How I treat patients with von Willebrand disease. Blood 2001; 97: 1915-1919.
    CrossrefPubMedGoogle Scholar
  • 4 Federici AB, Castaman G, Mannucci PM. Italian Association of Haemophilia Centers (AICE). Guidelines for the diagnosis and management of von Wille-brand disease in Italy. Haemophilia 2002; 08: 607-621.
    CrossrefPubMedGoogle Scholar
  • 5 Mannucci PM. Treatment of von Willebrand’s disease. N Engl J Med 2004; 351: 683-694.
    CrossrefPubMedGoogle Scholar
  • 6 Mannucci PM, Franchini M, Castaman G. et al. on behalf of AICE.. Evidence based recommendations on the treatment of von Willebrand disease in Italy. Blood Transfus 2009; 07: 117-126.
    PubMedGoogle Scholar
  • 7 Favaloro EJ, Franchini M, Lippi G. Biological therapies for von Willebrand disease. Expert Opin Biol Ther 2012; 12: 551-564.
    CrossrefPubMedGoogle Scholar
  • 8 Mannucci PM. Haemostatic drugs. N Engl J Med 1998; 339: 245-253.
    CrossrefPubMedGoogle Scholar
  • 9 Luo GP, Ni B, Yang X. et al. Von Willebrand factor: more than a regulator of haemostasis and thrombosis. Acta Haematol 2012; 128: 158-169.
    CrossrefPubMedGoogle Scholar
  • 10 Lenting P, Casari C, Christophe OD. et al. Von Willebrand factor: the old, the new and the unknown. J Thromb Haemost 2012; 10: 2428-2437.
    CrossrefPubMedGoogle Scholar
  • 11 Franchini M, Mannucci PM. Von Willebrand disease-associated angiodysplasia: a few answers, still many questions. Br J Haematol 2013; 161: 177-182.
    CrossrefPubMedGoogle Scholar
  • 12 Starke RD, Ferraro F, Paschalaki KE. et al. Endothelial von Willebrand factor regulates angiogenesis. Blood 2011; 117: 1071-1080.
    CrossrefPubMedGoogle Scholar
  • 13 Odouard S, Christophe OD, de Groot PG. et al. Identification of galectin-1 and galectin-3 as novel partner for von Willebrand factor. Arterioscler Thromb Vasc Biol 2012; 32: 894-901.
    CrossrefPubMedGoogle Scholar
  • 14 Pi L, Shenoy AK, Liu J. et al. CCN2/CTGF regulates neovessel formation via targeting structurally conserved cystine knot motifs in multiple angiogenic regulators. FASEB J 2012; 26: 3365-3379.
    CrossrefPubMedGoogle Scholar
  • 15 van Breevoort D, van Agtmaal EL, Dragt BS. et al. Proteomic screen identifies IGFBP7 as a novel component of endothelial cell- specific Weibel-Palade bodies. J Proteome Res 2012; 11: 2925-2936.
    CrossrefPubMedGoogle Scholar
  • 16 Gritti G, Cortelezzi A, Bucciarelli P. et al. Circulating and progenitor endothelial cells are abnormal in patients with different types of von Willebrand disease and correlate with markers of angiogenesis. Am J Hematol 2011; 86: 650-656.
    CrossrefPubMedGoogle Scholar
  • 17 Makris M. Gastrointestinal bleeding in von Willebrand disease. Thromb Res 2006; 118 (Suppl. 01) S13-17.
    CrossrefPubMedGoogle Scholar
  • 18 Warkentin TE, Moore JC, Anand SS. et al. Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfus Med Rev 2003; 17: 272-286.
    CrossrefPubMedGoogle Scholar
  • 19 Ramsay DM, Buist TA, Macleod DA. et al. Persistent gastrointestinal bleeding due to angiodysplasia of the gut in von Willebrand’s disease. Lancet 1976; 2: 275-278.
    PubMedGoogle Scholar
  • 20 Warkentin TE, Moore JC, Anand SS. et al. Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfusion Med Rev 2003; 17: 272-286.
    CrossrefPubMedGoogle Scholar
  • 21 Fressinaud E, Meyer D. International survey of patients with von Willebrand disease and angiodysplasia. Thromb Haemost 1993; 70: 546.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Castaman G, Federici AB, Tosetto A. et al. Different bleeding risk in type 2 A and 2 M Von Willebrand disease: a two-year prospective study in 107 patients. J Thromb Haemost 2012; 10: 632-638.
    CrossrefPubMedGoogle Scholar
  • 23 Satoh Y, Kita H, Kihira K. et al. Gastrointestinal angiodysplasia in a patient with type 2 von Willebrand’s disease and analysis of exon 28 of the von Willebrand factor gene. Am J Gastroenterol 2004; 99: 2495-2498.
    CrossrefPubMedGoogle Scholar
  • 24 Vincentelli A, Susen S, Le Tourneau T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-349.
    CrossrefPubMedGoogle Scholar
  • 25 Federici AB, Stabile F, Castaman G. et al. Tretament of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches. Blood 1998; 92: 2707-2711.
    PubMedGoogle Scholar
  • 26 Morris ES, Hampton KK, Nesbitt IM. et al. The management of von Willebrand’s disease associated gastrointestinal dysplasia. Blood Coagul Fibrinolysis 2001; 12: 143-148.
    CrossrefPubMedGoogle Scholar
  • 27 Berntorp E, Windyga J. European Wilate Study Group. Treatment and prevention of acute bleedings in von Willebrand disease--efficacy and safety of Wilate, a new generation von Willebrand factor/factor VIII concentrate. Haemophilia 2009; 15: 122-130.
    CrossrefPubMedGoogle Scholar
  • 28 Zanon E, Vianello F, Casonato A. et al. Early transfusion of factor VIII/von Willebrand factor concentrates seems to be effective in the treatment of gastrointestinal bleeding in patients with von Willebrand type III disease. Haemophilia 2001; 07: 500-503.
    CrossrefPubMedGoogle Scholar
  • 29 Boneu B, Fernandez F. The role of hematocrit in bleeding. Transfus Med Rev 1987; 01: 182-185.
    CrossrefPubMedGoogle Scholar
  • 30 Eugster M, Reinhart WH. The influence of the haematocrit on primary haemostasis in vitro. Thromb Haemost 2005; 94: 1213-1218.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Siragusa S, Malato A, Lo Coco L. et al. Gastrointestinal bleeding due to angiodysplasia in patients with type 1 von Willebrand disease: report on association and management. Haemophilia 2008; 14: 150-152.
    PubMedGoogle Scholar
  • 32 Meijer K, Peters FT, van der Meer J. Recurrent severe bleeding from gastrointestinal angiodysplasia in a patient with von Willebrand’s disease, controlled with recombinant factor VIIa. Blood Coagul Fibrinolysis 2001; 12: 211-213.
    CrossrefPubMedGoogle Scholar
  • 33 Castillo R, Monteagudo J, Escolar G. et al. Haemostatic effect of normal platelet transfusion in severe von Willebrand disease patients. Blood 1991; 07: 1901-1905.
    PubMedGoogle Scholar
  • 34 Franchini M, Targher G, Lippi G. Prophylaxis in von Willebrand disease. Ann Hematol 2007; 86: 699-704.
    CrossrefPubMedGoogle Scholar
  • 35 Federici AB. Prophylaxis of bleeding episodes in patients with von Willebrand’s disease. Blood Transfus 2008; 06 (Suppl. 02) s26-s32.
    PubMedGoogle Scholar
  • 36 Abshire T. The role of prophylaxis in the management of von Willebrand disease: today and tomorrow. Thromb Res 2009; 124 (Suppl. 01) S15-S19.
    CrossrefPubMedGoogle Scholar
  • 37 Berntorp E, Petrini P. Long-term prophylaxis in von Willebrand disease. Blood Coagul Fibrinolysis 2005; 16 (Suppl. 01) S23-S26.
    CrossrefPubMedGoogle Scholar
  • 38 Federici AB, Gianniello F, Mannucci PM. Secondary long-term prophylaxis in severe patients with von Willebrand’s disease: an Italian cohort study. Haematologica Reports 2005; 01: 15-20.
    PubMedGoogle Scholar
  • 39 Federici AB, Castaman G, Franchini M. et al. Clinical use of Haemate P in inherited von Willebrand disease: a cohort study on 100 Italian patients. Haematologica 2007; 92: 944-951.
    CrossrefPubMedGoogle Scholar
  • 40 Abshire TC, Federici AB, Alvárez MT. et al. VWD, PN. Prophylaxis in severe forms of von Willebrand’s disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN). Haemophilia 2013; 19: 76-81.
    CrossrefPubMedGoogle Scholar
  • 41 Mannucci PM, Pareti FI, Holmberg L. et al. Studies on the prolonged bleeding time in von Willebrand’s disease. J Lab Clin Med 1976; 88: 662-671.
    PubMedGoogle Scholar
  • 42 Chey WD, Hasler WL, Bockenstedt PL. Angiodysplasia and von Willebrand’s disease type IIB treated with estrogen/progesterone therapy. Am J Hematol 1992; 41: 276-279.
    CrossrefPubMedGoogle Scholar
  • 43 Bowers M, McNulty O, Mayne E. Octreotide in the treatment of gastrointestinal bleeding caused by angiodysplasia in two patients with von Willebrand’s disease. Br J Haematol 2000; 108: 524-527.
    CrossrefPubMedGoogle Scholar
  • 44 Franchini M, Frattini F, Crestani S. et al. Novel treatments for epistaxis in hereditary haemorrhagic telangiectasia: a systematic review of the clinical experience with thalidomide. J Thromb Thrombolysis 2013; 36: 355-357.
    CrossrefPubMedGoogle Scholar
  • 45 Hirri HM, Green PJ, Lindsay J. Von Willebrand’s disease and angiodysplasia treated with thalidomide. Haemophilia 2006; 12: 285-286.
    CrossrefPubMedGoogle Scholar
  • 46 Nomikou E, Tsevrenis V, Gafou A. et al. Type IIb von Willebrand disease with angiodysplasias and refractory gastrointestinal bleeding successfully treated with thalidomide. Haemophilia 2009; 15: 1340-1342.
    CrossrefPubMedGoogle Scholar
  • 47 Alikhan R, Keeling D. Von Willebrand disease, angiodysplasia and atorvastatin. Br J Haematol 2009; 149: 159-160.
    PubMedGoogle Scholar
  • 48 Sohal M, Laffan M. Von Willebrand disease and angiodysplasia responding to atorvastatin. Br J Haematol 2008; 142: 309.
    CrossrefPubMedGoogle Scholar
  • 49 Mannucci PM, Tenconi PM, Castaman G. et al. Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial. Blood 1992; 79: 3130-3137.
    PubMedGoogle Scholar
  • 50 Mannucci PM, Kempton C, Millar C. et al. Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial. Blood 2013; 122: 648-657.
    CrossrefPubMedGoogle Scholar
  • 51 Mannucci PM, Pareti FI, Holmberg L. et al. Studies on the prolonged bleeding time in von Willebrand’s disease. J Lab Clin Med 1976; 88: 662-671.
    PubMedGoogle Scholar