Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000077.xml
Download PDF
Semin Thromb Hemost 2017; 43(06): 572-580
DOI: 10.1055/s-0037-1599145
DOI: 10.1055/s-0037-1599145
Review Article
Angiodysplasia in von Willebrand Disease: Understanding the Clinical and Basic Science
Further Information
Publication History
Publication Date:
05 May 2017 (online)
Abstract
Severe and intractable gastrointestinal bleeding caused by angiodysplasia is a debilitating problem for up to 20% of patients with von Willebrand disease (VWD). Currently, the lack of an optimal treatment for this recurrent problem presents an ongoing challenge for many physicians in their management of affected patients. Over the past few years, studies have pointed to a regulatory role for the hemostatic protein, von Willebrand factor (VWF), in angiogenesis, providing a novel target for the modulation of vessel development. This article will review the clinical implications and molecular pathology of angiodysplasia in VWD.
-
References
- 1 Wagner DD, Olmsted JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 1982; 95 (01) 355-360
- 2 Kanaji S, Fahs SA, Shi Q, Haberichter SL, Montgomery RR. Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis. J Thromb Haemost 2012; 10 (08) 1646-1652
- 3 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424
- 4 Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 1996; 87 (10) 4223-4234
- 5 Sadler JE. von Willebrand factor assembly and secretion. J Thromb Haemost 2009; 7 (Suppl. 01) 24-27
- 6 Lenting PJ, Casari C, Christophe OD, Denis CV. von Willebrand factor: the old, the new and the unknown. J Thromb Haemost 2012; 10 (12) 2428-2437
- 7 Casari C, Lenting PJ, Christophe OD, Denis CV. Von Willebrand factor abnormalities studied in the mouse model: what we learned about VWF functions. Mediterr J Hematol Infect Dis 2013; 5 (01) e2013047
- 8 von Willebrand EA. Hereditar pseudohemofili. Fin Lakarsallskapets Handl 1926; 67 (07) 87-112
- 9 Fressinaud E, Meyer D. International survey of patients with von Willebrand disease and angiodysplasia. Thromb Haemost 1993; 70 (03) 546
- 10 Bowman M, Hopman WM, Rapson D, Lillicrap D, James P. The prevalence of symptomatic von Willebrand disease in primary care practice. J Thromb Haemost 2010; 8 (01) 213-216
- 11 James PD, Goodeve AC. von Willebrand disease. Genet Med 2011; 13 (05) 365-376
- 12 James PD, Lillicrap D. The molecular characterization of von Willebrand disease: good in parts. Br J Haematol 2013; 161 (02) 166-176
- 13 James PD, Notley C, Hegadorn C. , et al. The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study. Blood 2007; 109 (01) 145-154
- 14 Sadler JE, Budde U, Eikenboom JC. , et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4 (10) 2103-2114
- 15 Bowman M, Tuttle A, Notley C. , et al; Association of Hemophilia Clinic Directors of Canada. The genetics of Canadian type 3 von Willebrand disease: further evidence for co-dominant inheritance of mutant alleles. J Thromb Haemost 2013; 11 (03) 512-520
- 16 Franchini M, Mannucci PM. Von Willebrand disease-associated angiodysplasia: a few answers, still many questions. Br J Haematol 2013; 161 (02) 177-182
- 17 Quick AJ. Telangiectasia: its relationship to the Minot-von Willebrand syndrome. Am J Med Sci 1967; 254 (05) 585-601
- 18 Koscielny JK, Latza R, Mürsdorf S. , et al. Capillary microscopic and rheological dimensions for the diagnosis of von Willebrand disease in comparison to other haemorrhagic diatheses. Thromb Haemost 2000; 84 (06) 981-988
- 19 Lemesh RA. Case report: recurrent hematuria and hematospermia due to prostatic telangiectasia in classic von Willebrand's disease. Am J Med Sci 1993; 306 (01) 35-36
- 20 Conlon CL, Weinger RS, Cimo PL, Moake JL, Olson JD. Telangiectasia and von Willebrand's disease in two families. Ann Intern Med 1978; 89 (06) 921-924
- 21 Ramsay DM, Buist TAS, Macleod DAD, Heading RC. Persistent gastrointestinal bleeding due to angiodysplasia of the gut in von Willebrand's disease. Lancet 1976; 2 (7980): 275-278
- 22 Castaman G, Federici AB, Tosetto A. , et al. Different bleeding risk in type 2A and 2M von Willebrand disease: a 2-year prospective study in 107 patients. J Thromb Haemost 2012; 10 (04) 632-638
- 23 Warkentin TE, Moore JC, Anand SS, Lonn EM, Morgan DG. Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfus Med Rev 2003; 17 (04) 272-286
- 24 Makris M. Gastrointestinal bleeding in von Willebrand disease. Thromb Res 2006; 118 (Suppl. 01) S13-S17
- 25 Franchini M, Mannucci PM. Gastrointestinal angiodysplasia and bleeding in von Willebrand disease. Thromb Haemost 2014; 112 (03) 427-431
- 26 Boley SJ, Sammartano R, Adams A, DiBiase A, Kleinhaus S, Sprayregen S. On the nature and etiology of vascular ectasias of the colon. Degenerative lesions of aging. Gastroenterology 1977; 72 (4, Pt 1): 650-660
- 27 Starke RD, Ferraro F, Paschalaki KE. , et al. Endothelial von Willebrand factor regulates angiogenesis. Blood 2011; 117 (03) 1071-1080
- 28 Zanon E, Vianello F, Casonato A, Girolami A. 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; 7 (05) 500-503
- 29 Foutch PG, Rex DK, Lieberman DA. Prevalence and natural history of colonic angiodysplasia among healthy asymptomatic people. Am J Gastroenterol 1995; 90 (04) 564-567
- 30 Makris M, Federici AB, Mannucci PM. , et al. The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease. Haemophilia 2015; 21 (03) 338-342
- 31 Simone JV, Cornet JA, Abildgaard CF. Acquired von Willebrand's syndrome in systemic lupus erythematosus. Blood 1968; 31 (06) 806-812
- 32 Federici AB, Rand JH, Bucciarelli P. , et al; Subcommittee on von Willebrand Factor. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 2000; 84 (02) 345-349
- 33 Fricke WA, Brinkhous KM, Garris JB, Roberts HR. Comparison of inhibitory and binding characteristics of an antibody causing acquired von Willebrand syndrome: an assay for von Willebrand factor binding by antibody. Blood 1985; 66 (03) 562-569
- 34 Lazarchick J, Pappas AA, Kizer J, Hall SA. Acquired von Willebrand syndrome due to an inhibitor specific for von Willebrand factor antigens. Am J Hematol 1986; 21 (03) 305-314
- 35 Mohri H, Ohkubo T. Acquired von Willebrand's syndrome due to an inhibitor of IgG specific for von Willebrand's factor in polycythemia rubra vera. Acta Haematol 1987; 78 (04) 258-264
- 36 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 (02) 227-233
- 37 Mannucci PM, Lombardi R, Bader R. , et al. Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. Blood 1984; 64 (03) 614-621
- 38 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 (10) 3378-3384
- 39 Coleman R, Favaloro EJ, Soltani S, Keng TB. Acquired von Willebrand disease: potential contribution of the VWF:CB to the identification of functionally inhibiting auto-antibodies to von Willebrand factor. J Thromb Haemost 2006; 4 (09) 2085-2088
- 40 Guerin V, Ryman A, Velez F. Acquired von Willebrand disease: potential contribution of the von Willebrand factor collagen-binding to the identification of functionally inhibiting auto-antibodies to von Willebrand factor: a rebuttal. J Thromb Haemost 2008; 6 (06) 1051-1052
- 41 Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood 1994; 83 (08) 2171-2179
- 42 Wu T, Lin J, Cruz MA, Dong JF, Zhu C. Force-induced cleavage of single VWFA1A2A3 tridomains by ADAMTS-13. Blood 2010; 115 (02) 370-378
- 43 Yoshida K, Tobe S, Kawata M, Yamaguchi M. Acquired and reversible von Willebrand disease with high shear stress aortic valve stenosis. Ann Thorac Surg 2006; 81 (02) 490-494
- 44 Michiels JJ, Schroyens W, Berneman Z, van der Planken M. Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after treatment with thyroxine. Clin Appl Thromb Hemost 2001; 7 (02) 113-115
- 45 Schödel J, Obergfell A, Maass AH. Severe aortic valve stenosis and nosebleed. Int J Cardiol 2007; 120 (02) 286-287
- 46 Veyradier A, Balian A, Wolf M. , et al. Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract. Gastroenterology 2001; 120 (02) 346-353
- 47 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 (11) 1290-1295
- 48 Vincentelli A, Susen S, Le Tourneau T. , et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349 (04) 343-349
- 49 Slaughter MS. Hematologic effects of continuous flow left ventricular assist devices. J Cardiovasc Transl Res 2010; 3 (06) 618-624
- 50 Heyde E. Gastrointestinal bleeding in aortic stenosis. N Engl J Med 1958; 259: 196
- 51 Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link?. Lancet 1992; 340 (8810): 35-37
- 52 Crawley JTB, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood 2011; 118 (12) 3212-3221
- 53 Panzer S, Badr Eslam R, Schneller A. , et al. Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis. Thromb Haemost 2010; 103 (02) 408-414
- 54 Massyn MW, Khan SA. Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age Ageing 2009; 38 (03) 267-270 , discussion 251
- 55 King RM, Pluth JR, Giuliani ER. The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. Ann Thorac Surg 1987; 44 (05) 514-516
- 56 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 (01) 122-130
- 57 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 (01) 76-81
- 58 Mannucci PM, Pareti FI, Holmberg L, Nilsson IM, Ruggeri ZM. Studies on the prolonged bleeding time in von Willebrand's disease. J Lab Clin Med 1976; 88 (04) 662-671
- 59 Plaimauer B, Schlokat U, Turecek PL. , et al. Recombinant von Willebrand factor: preclinical development. Semin Thromb Hemost 2001; 27 (04) 395-403
- 60 Mannucci PM, Kempton C, Millar C. , et al; rVWF Ad Hoc Study Group. Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial. Blood 2013; 122 (05) 648-657
- 61 Morris ES, Hampton KK, Nesbitt IM, Preston FE, Thomas EG, Makris M. The management of von Willebrand's disease-associated gastrointestinal angiodysplasia. Blood Coagul Fibrinolysis 2001; 12 (02) 143-148
- 62 Nomikou E, Tsevrenis V, Gafou A, Bellia M, Theodossiades G. Type IIb von Willebrand disease with angiodysplasias and refractory gastrointestinal bleeding successfully treated with thalidomide. Haemophilia 2009; 15 (06) 1340-1342
- 63 Bauditz J, Schachschal G, Wedel S, Lochs H. Thalidomide for treatment of severe intestinal bleeding. Gut 2004; 53 (04) 609-612
- 64 Alikhan R, Keeling D. Von Willebrand disease, angiodysplasia and atorvastatin. Br J Haematol 2010; 149 (01) 159-160
- 65 Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001; 280 (06) C1358-C1366
- 66 Junquera F, Saperas E, de Torres I, Vidal MT, Malagelada J-R. Increased expression of angiogenic factors in human colonic angiodysplasia. Am J Gastroenterol 1999; 94 (04) 1070-1076
- 67 Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003; 9 (06) 677-684
- 68 Semenza GL. Transcriptional regulation by hypoxia-inducible factor 1 molecular mechanisms of oxygen homeostasis. Trends Cardiovasc Med 1996; 6 (05) 151-157
- 69 Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006; 7 (05) 359-371
- 70 Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9 (06) 685-693
- 71 Hansen TM, Singh H, Tahir TA, Brindle NP. Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface. Cell Signal 2010; 22 (03) 527-532
- 72 Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219 (4587): 983-985
- 73 Thurston G, Suri C, Smith K. , et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 1999; 286 (5449): 2511-2514
- 74 Fiedler U, Scharpfenecker M, Koidl S. , et al. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 2004; 103 (11) 4150-4156
- 75 Holash J, Wiegand SJ, Yancopoulos GD. New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene 1999; 18 (38) 5356-5362
- 76 Somanath PR, Malinin NL, Byzova TV. Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis. Angiogenesis 2009; 12 (02) 177-185
- 77 Huang J, Roth R, Heuser JE, Sadler JE. Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress. Blood 2009; 113 (07) 1589-1597
- 78 Brooks PC, Strömblad S, Klemke R, Visscher D, Sarkar FH, Cheresh DA. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. J Clin Invest 1995; 96 (04) 1815-1822
- 79 Hodivala-Dilke K. alphavbeta3 integrin and angiogenesis: a moody integrin in a changing environment. Curr Opin Cell Biol 2008; 20 (05) 514-519
- 80 Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9 (06) 653-660
- 81 Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011; 146 (06) 873-887
- 82 Randi AM, Laffan MA, Starke RD. Von Willebrand factor, angiodysplasia and angiogenesis. Mediterr J Hematol Infect Dis 2013; 5 (01) e2013060
- 83 Thomas M, Felcht M, Kruse K. , et al. Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation. J Biol Chem 2010; 285 (31) 23842-23849
- 84 Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci U S A 2002; 99 (17) 11205-11210
- 85 Reynolds LE, Wyder L, Lively JC. , et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 2002; 8 (01) 27-34
- 86 Wang JW, Eikenboom J. Von Willebrand disease and Weibel-Palade bodies. Hamostaseologie 2010; 30 (03) 150-155
- 87 Wang JW, Valentijn KM, de Boer HC. , et al. Intracellular storage and regulated secretion of von Willebrand factor in quantitative von Willebrand disease. J Biol Chem 2011; 286 (27) 24180-24188
- 88 Michaux G, Hewlett LJ, Messenger SL. , et al. Analysis of intracellular storage and regulated secretion of 3 von Willebrand disease-causing variants of von Willebrand factor. Blood 2003; 102 (07) 2452-2458
- 89 Haberichter SL, Allmann AM, Jozwiak MA, Montgomery RR, Gill JC. Genetic alteration of the D2 domain abolishes von Willebrand factor multimerization and trafficking into storage. J Thromb Haemost 2009; 7 (04) 641-650
- 90 Jeanneau C, Avner P, Sultan Y. Use of monoclonal antibody and colloidal gold in E.M. localization of von Willebrand factor in megakaryocytes and platelets. Cell Biol Int Rep 1984; 8 (10) 841-848
- 91 Haberichter SL, Budde U, Obser T, Schneppenheim S, Wermes C, Schneppenheim R. The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF. Blood 2010; 115 (22) 4580-4587
- 92 Castaman G, Giacomelli SH, Jacobi P. , et al. Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotype. J Thromb Haemost 2010; 8 (09) 2011-2016
- 93 Berber E, James PD, Hough C, Lillicrap D. An assessment of the pathogenic significance of the R924Q von Willebrand factor substitution. J Thromb Haemost 2009; 7 (10) 1672-1679
- 94 Booyse FM, Quarfoot AJ, Chediak J, Stemerman MB, Maciag T. Characterization and properties of cultured human von Willebrand umbilical vein endothelial cells. Blood 1981; 58 (04) 788-796
- 95 Ewenstein BM, Inbal A, Pober JS, Handin RI. Molecular studies of von Willebrand disease: reduced von Willebrand factor biosynthesis, storage, and release in endothelial cells derived from patients with type I von Willebrand disease. Blood 1990; 75 (07) 1466-1472
- 96 Federici AB, de Groot PG, Moia M, Ijsseldijk MJ, Sixma JJ, Mannucci PM. Type I von Willebrand disease, subtype ‘platelet low’: decreased platelet adhesion can be explained by low synthesis of von Willebrand factor in endothelial cells. Br J Haematol 1993; 83 (01) 88-93
- 97 de Groot PG, Federici AB, de Boer HC, d'Alessio P, Mannucci PM, Sixma JJ. von Willebrand factor synthesized by endothelial cells from a patient with type IIB von Willebrand disease supports platelet adhesion normally but has an increased affinity for platelets. Proc Natl Acad Sci U S A 1989; 86 (10) 3793-3797
- 98 Levene RB, Booyse FM, Chediak J, Zimmerman TS, Livingston DM, Lynch DC. Expression of abnormal von Willebrand factor by endothelial cells from a patient with type IIA von Willebrand disease. Proc Natl Acad Sci U S A 1987; 84 (18) 6550-6554
- 99 Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105 (01) 71-77
- 100 Wang JW, Bouwens EA, Pintao MC. , et al. Analysis of the storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from patients with von Willebrand disease. Blood 2013; 121 (14) 2762-2772
- 101 Starke RD, Paschalaki KE, Dyer CEF. , et al. Cellular and molecular basis of von Willebrand disease: studies on blood outgrowth endothelial cells. Blood 2013; 121 (14) 2773-2784
- 102 Groeneveld DJ, van Bekkum T, Dirven RJ. , et al. Angiogenic characteristics of blood outgrowth endothelial cells from patients with von Willebrand disease. J Thromb Haemost 2015; 13 (10) 1854-1866
- 103 Selvam SN, Casey L, Bowman M. , et al. Abnormal angiogenesis in blood outgrowth endothelial cells derived from von Willebrand disease patients. Blood Coagul Fibrinolysis 2017;