Skip to main content
Top
Published in: International Journal of Hematology 4/2012

01-04-2012 | Progress in Hematology

von Willebrand factor: at the crossroads of bleeding and thrombosis

Authors: Cécile V. Denis, Peter J. Lenting

Published in: International Journal of Hematology | Issue 4/2012

Login to get access

Abstract

Hemostasis and thrombosis represent two sides of the same coin. Hemostasis maintains blood fluidity in the vascular system while allowing for rapid thrombus formation to prevent excessive hemorrhage after blood vessel injury. Thrombosis is a pathologic extension of the normal hemostatic mechanism, occurring when unwanted clot formation develops in certain pathological situations. The molecular mechanisms underlying both phenomena are fundamentally identical. One of the key players in both processes is the plasma glycoprotein von Willebrand factor, which perfectly illustrates this duality between hemostatic and thrombotic mechanisms. The purpose of this review is to discuss novel findings on the role of von Willebrand factor at this interface, and how some of these findings may help develop new therapeutic strategies.
Literature
1.
go back to reference Reininger AJ. Function of von Willebrand factor in haemostasis and thrombosis. Haemophilia. 2008;14(Suppl 5):11–26.PubMedCrossRef Reininger AJ. Function of von Willebrand factor in haemostasis and thrombosis. Haemophilia. 2008;14(Suppl 5):11–26.PubMedCrossRef
3.
go back to reference Lenting PJ, Van Schooten CJ, Denis CV. Clearance mechanisms of von Willebrand factor and factor VIII. J Thromb Haemost. 2007;5:1353–60.PubMedCrossRef Lenting PJ, Van Schooten CJ, Denis CV. Clearance mechanisms of von Willebrand factor and factor VIII. J Thromb Haemost. 2007;5:1353–60.PubMedCrossRef
4.
5.
go back to reference Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VIII/von Willebrand factor. Blood. 1981;57:1140–3.PubMed Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VIII/von Willebrand factor. Blood. 1981;57:1140–3.PubMed
6.
go back to reference Furlan M. von Willebrand factor: molecular size and functional activity. Ann Hematol. 1996;72:341–8.PubMedCrossRef Furlan M. von Willebrand factor: molecular size and functional activity. Ann Hematol. 1996;72:341–8.PubMedCrossRef
7.
go back to reference Barr J, Motto D. Modulation of von Willebrand factor by ADAMTS13. In: Federici AB, Lee CA, Berntorp EE, Lillicrap D, Montgomery RR, editors. Von Willebrand disease: basic and clinical aspects. Chichester: Wiley-Blackwell; 2011. p. 49–62.CrossRef Barr J, Motto D. Modulation of von Willebrand factor by ADAMTS13. In: Federici AB, Lee CA, Berntorp EE, Lillicrap D, Montgomery RR, editors. Von Willebrand disease: basic and clinical aspects. Chichester: Wiley-Blackwell; 2011. p. 49–62.CrossRef
8.
go back to reference Springer TA. Biology and physics of von Willebrand factor concatamers. J Thromb Haemost. 2011;9(Suppl 1):130–43.PubMedCrossRef Springer TA. Biology and physics of von Willebrand factor concatamers. J Thromb Haemost. 2011;9(Suppl 1):130–43.PubMedCrossRef
9.
go back to reference Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, 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;4:2103–14.PubMedCrossRef Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, 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;4:2103–14.PubMedCrossRef
10.
go back to reference Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update. Semin Hematol. 2005;42:15–28.PubMedCrossRef Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update. Semin Hematol. 2005;42:15–28.PubMedCrossRef
11.
go back to reference Schneppenheim R, Budde U. von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein. J Thromb Haemost. 2011;9(Suppl 1):209–15.PubMedCrossRef Schneppenheim R, Budde U. von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein. J Thromb Haemost. 2011;9(Suppl 1):209–15.PubMedCrossRef
12.
go back to reference Rayes J, Hommais A, Legendre P, Tout H, Veyradier A, Obert B, et al. Effect of von Willebrand disease type 2B and type 2M mutations on the susceptibility of von Willebrand factor to ADAMTS-13. J Thromb Haemost. 2007;5:321–8.PubMedCrossRef Rayes J, Hommais A, Legendre P, Tout H, Veyradier A, Obert B, et al. Effect of von Willebrand disease type 2B and type 2M mutations on the susceptibility of von Willebrand factor to ADAMTS-13. J Thromb Haemost. 2007;5:321–8.PubMedCrossRef
13.
go back to reference Federici AB, Mannucci PM, Castaman G, Baronciani L, Bucciarelli P, Canciani MT, et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood. 2009;113:526–34.PubMedCrossRef Federici AB, Mannucci PM, Castaman G, Baronciani L, Bucciarelli P, Canciani MT, et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood. 2009;113:526–34.PubMedCrossRef
14.
go back to reference Rayes J, Hollestelle MJ, Legendre P, Marx I, de Groot PG, Christophe OD, et al. Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B. Blood. 2010;115:4870–7.PubMedCrossRef Rayes J, Hollestelle MJ, Legendre P, Marx I, de Groot PG, Christophe OD, et al. Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B. Blood. 2010;115:4870–7.PubMedCrossRef
15.
go back to reference Nishino M, Girma JP, Rothschild C, Fressinaud E, Meyer D. New variant of von Willebrand disease with defective binding to factor VIII. Blood. 1989;74:1591–9.PubMed Nishino M, Girma JP, Rothschild C, Fressinaud E, Meyer D. New variant of von Willebrand disease with defective binding to factor VIII. Blood. 1989;74:1591–9.PubMed
16.
go back to reference Flood VH, Lederman CA, Wren JS, Christopherson PA, Friedman KD, Hoffmann RG, et al. Absent collagen binding in a VWF A3 domain mutant: utility of the VWF:CB in diagnosis of VWD. J Thromb Haemost. 2010;8:1431–3.PubMedCrossRef Flood VH, Lederman CA, Wren JS, Christopherson PA, Friedman KD, Hoffmann RG, et al. Absent collagen binding in a VWF A3 domain mutant: utility of the VWF:CB in diagnosis of VWD. J Thromb Haemost. 2010;8:1431–3.PubMedCrossRef
17.
go back to reference Ribba AS, Loisel I, Lavergne JM, Juhan-Vague I, Obert B, Cherel G, et al. Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thromb Haemost. 2001;86:848–54.PubMed Ribba AS, Loisel I, Lavergne JM, Juhan-Vague I, Obert B, Cherel G, et al. Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thromb Haemost. 2001;86:848–54.PubMed
18.
go back to reference Riddell AF, Gomez K, Millar CM, Mellars G, Gill S, Brown SA, et al. Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor. Blood. 2009;114:3489–96.PubMedCrossRef Riddell AF, Gomez K, Millar CM, Mellars G, Gill S, Brown SA, et al. Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor. Blood. 2009;114:3489–96.PubMedCrossRef
19.
go back to reference Marx I, Christophe OD, Lenting PJ, Rupin A, Vallez MO, Verbeuren TJ, et al. Altered thrombus formation in von Willebrand factor-deficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa. Blood. 2008;112:603–9.PubMedCrossRef Marx I, Christophe OD, Lenting PJ, Rupin A, Vallez MO, Verbeuren TJ, et al. Altered thrombus formation in von Willebrand factor-deficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa. Blood. 2008;112:603–9.PubMedCrossRef
20.
go back to reference Casonato A, Pontara E, Sartorello F, Cattini MG, Sartori MT, Padrini R, et al. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease. Blood. 2002;99:180–4.PubMedCrossRef Casonato A, Pontara E, Sartorello F, Cattini MG, Sartori MT, Padrini R, et al. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease. Blood. 2002;99:180–4.PubMedCrossRef
21.
go back to reference Lenting PJ, Westein E, Terraube V, Ribba AS, Huizinga EG, Meyer D, et al. An experimental model to study the in vivo survival of von Willebrand factor. Basic aspects and application to the R1205H mutation. J Biol Chem. 2004;279:12102–9.PubMedCrossRef Lenting PJ, Westein E, Terraube V, Ribba AS, Huizinga EG, Meyer D, et al. An experimental model to study the in vivo survival of von Willebrand factor. Basic aspects and application to the R1205H mutation. J Biol Chem. 2004;279:12102–9.PubMedCrossRef
22.
go back to reference Pruss CM, Golder M, Bryant A, Hegadorn CA, Burnett E, Laverty K, et al. Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models. Blood. 2011;117:4358–66.PubMedCrossRef Pruss CM, Golder M, Bryant A, Hegadorn CA, Burnett E, Laverty K, et al. Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models. Blood. 2011;117:4358–66.PubMedCrossRef
23.
go back to reference Denis CV, Christophe OD, Oortwijn BD, Lenting PJ. Clearance of von Willebrand factor. Thromb Haemost. 2008;99:271–8.PubMed Denis CV, Christophe OD, Oortwijn BD, Lenting PJ. Clearance of von Willebrand factor. Thromb Haemost. 2008;99:271–8.PubMed
24.
go back to reference Haberichter SL, Castaman G, Budde U, Peake I, Goodeve A, Rodeghiero F, et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood. 2008;111:4979–85.PubMedCrossRef Haberichter SL, Castaman G, Budde U, Peake I, Goodeve A, Rodeghiero F, et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood. 2008;111:4979–85.PubMedCrossRef
25.
go back to reference Van Schooten CJ, Tjernberg P, Westein E, Terraube V, Castaman G, Mourik JA, et al. Cysteine-mutations in von Willebrand factor associated with increased clearance. J Thromb Haemost. 2005;3:2228–37.PubMedCrossRef Van Schooten CJ, Tjernberg P, Westein E, Terraube V, Castaman G, Mourik JA, et al. Cysteine-mutations in von Willebrand factor associated with increased clearance. J Thromb Haemost. 2005;3:2228–37.PubMedCrossRef
26.
go back to reference Federici AB, Bucciarelli P, Castaman G, Baronciani L, Canciani MT, Mazzucconi MG, et al. Management of inherited von Willebrand disease in Italy: results from the retrospective study on 1234 patients. Semin Thromb Hemost. 2011;37:511–21.PubMedCrossRef Federici AB, Bucciarelli P, Castaman G, Baronciani L, Canciani MT, Mazzucconi MG, et al. Management of inherited von Willebrand disease in Italy: results from the retrospective study on 1234 patients. Semin Thromb Hemost. 2011;37:511–21.PubMedCrossRef
27.
go back to reference Castaman G, Tosetto A, Federici AB, Rodeghiero F. Bleeding tendency and efficacy of anti-haemorrhagic treatments in patients with type 1 von Willebrand disease and increased von Willebrand factor clearance. Thromb Haemost. 2011;105:647–54.PubMedCrossRef Castaman G, Tosetto A, Federici AB, Rodeghiero F. Bleeding tendency and efficacy of anti-haemorrhagic treatments in patients with type 1 von Willebrand disease and increased von Willebrand factor clearance. Thromb Haemost. 2011;105:647–54.PubMedCrossRef
28.
go back to reference Shetty S, Kasatkar P, Ghosh K. Pathophysiology of acquired von Willebrand disease: a concise review. Eur J Haematol. 2011;87:99–106.PubMedCrossRef Shetty S, Kasatkar P, Ghosh K. Pathophysiology of acquired von Willebrand disease: a concise review. Eur J Haematol. 2011;87:99–106.PubMedCrossRef
29.
go back to reference Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood. 2011;117:6777–85.PubMedCrossRef Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood. 2011;117:6777–85.PubMedCrossRef
30.
go back to reference Budde U, Scharf RE, Franke P, Hartmann-Budde K, Dent J, Ruggeri ZM. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood. 1993;82:1749–57.PubMed Budde U, Scharf RE, Franke P, Hartmann-Budde K, Dent J, Ruggeri ZM. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood. 1993;82:1749–57.PubMed
31.
go back to reference Richard C, Cuadrado MA, Prieto M, Batlle J, Lopez Fernandez MF, Rodriguez Salazar ML, et al. Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells. Am J Hematol. 1990;35:114–7.PubMedCrossRef Richard C, Cuadrado MA, Prieto M, Batlle J, Lopez Fernandez MF, Rodriguez Salazar ML, et al. Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells. Am J Hematol. 1990;35:114–7.PubMedCrossRef
32.
go back to reference Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood. 1986;67:758–61.PubMed Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood. 1986;67:758–61.PubMed
33.
go back to reference Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand’s disease the link? Lancet. 1992;340:35–7.PubMedCrossRef Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand’s disease the link? Lancet. 1992;340:35–7.PubMedCrossRef
34.
go back to reference 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;349:343–9.PubMedCrossRef 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;349:343–9.PubMedCrossRef
35.
go back to reference Banerjee AK. Angiodysplasia associated with hypertrophic obstructive cardiomyopathy (HOCM). Br J Clin Pract. 1990;44:326–7.PubMed Banerjee AK. Angiodysplasia associated with hypertrophic obstructive cardiomyopathy (HOCM). Br J Clin Pract. 1990;44:326–7.PubMed
36.
go back to reference Le Tourneau T, Susen S, Caron C, Millaire A, Marechaux S, Polge AS, et al. Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction. Circulation. 2008;118:1550–7.PubMedCrossRef Le Tourneau T, Susen S, Caron C, Millaire A, Marechaux S, Polge AS, et al. Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction. Circulation. 2008;118:1550–7.PubMedCrossRef
37.
go back to reference Slaughter MS. Hematologic effects of continuous flow left ventricular assist devices. J Cardiovasc Transl Res. 2010;3:618–24.PubMedCrossRef Slaughter MS. Hematologic effects of continuous flow left ventricular assist devices. J Cardiovasc Transl Res. 2010;3:618–24.PubMedCrossRef
38.
go back to reference Pareti FI, Lattuada A, Bressi C, Zanobini M, Sala A, Steffan A, et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation. 2000;102:1290–5.PubMed Pareti FI, Lattuada A, Bressi C, Zanobini M, Sala A, Steffan A, et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation. 2000;102:1290–5.PubMed
39.
go back to reference Zhang X, Halvorsen K, Zhang CZ, Wong WP, Springer TA. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science. 2009;324:1330–4.PubMedCrossRef Zhang X, Halvorsen K, Zhang CZ, Wong WP, Springer TA. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science. 2009;324:1330–4.PubMedCrossRef
40.
go back to reference van Schie MC, van Loon JE, de Maat MP, Leebeek FW. Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review. J Thromb Haemost. 2011;9:899–908.PubMedCrossRef van Schie MC, van Loon JE, de Maat MP, Leebeek FW. Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review. J Thromb Haemost. 2011;9:899–908.PubMedCrossRef
41.
go back to reference De Meyer SF, De Maeyer B, Deckmyn H, Vanhoorelbeke K. Von Willebrand factor: drug and drug target. Cardiovasc Hematol Disord: Drug Targets. 2009;9:9–20.CrossRef De Meyer SF, De Maeyer B, Deckmyn H, Vanhoorelbeke K. Von Willebrand factor: drug and drug target. Cardiovasc Hematol Disord: Drug Targets. 2009;9:9–20.CrossRef
42.
go back to reference Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Yudkin JS, Nijpels G, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscler Thromb Vasc Biol. 1999;19:3071–8.PubMedCrossRef Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Yudkin JS, Nijpels G, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscler Thromb Vasc Biol. 1999;19:3071–8.PubMedCrossRef
43.
go back to reference Wiman B, Andersson T, Hallqvist J, Reuterwall C, Ahlbom A, de Faire U. Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. Arterioscler Thromb Vasc Biol. 2000;20:2019–23.PubMedCrossRef Wiman B, Andersson T, Hallqvist J, Reuterwall C, Ahlbom A, de Faire U. Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. Arterioscler Thromb Vasc Biol. 2000;20:2019–23.PubMedCrossRef
44.
go back to reference Klemm T, Mehnert AK, Siegemund A, Wiesner TD, Gelbrich G, Bluher M, et al. Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes. 2005;113:568–72.PubMedCrossRef Klemm T, Mehnert AK, Siegemund A, Wiesner TD, Gelbrich G, Bluher M, et al. Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes. 2005;113:568–72.PubMedCrossRef
45.
go back to reference Lacquemant C, Gaucher C, Delorme C, Chatellier G, Gallois Y, Rodier M, et al. Association between high von willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes. The GENEDIAB Study Group and the DESIR Study Group. Kidney Int. 2000;57:1437–43.PubMedCrossRef Lacquemant C, Gaucher C, Delorme C, Chatellier G, Gallois Y, Rodier M, et al. Association between high von willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes. The GENEDIAB Study Group and the DESIR Study Group. Kidney Int. 2000;57:1437–43.PubMedCrossRef
46.
go back to reference van der Meer IM, Brouwers GJ, Bulk S, Leebeek FW, van der Kuip DA, Hofman A, et al. Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study. Br J Haematol. 2004;124:343–7.PubMedCrossRef van der Meer IM, Brouwers GJ, Bulk S, Leebeek FW, van der Kuip DA, Hofman A, et al. Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study. Br J Haematol. 2004;124:343–7.PubMedCrossRef
47.
go back to reference Smith NL, Rice KM, Bovill EG, Cushman M, Bis JC, McKnight B, et al. Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood. 2011;117:6007–11.PubMedCrossRef Smith NL, Rice KM, Bovill EG, Cushman M, Bis JC, McKnight B, et al. Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood. 2011;117:6007–11.PubMedCrossRef
48.
go back to reference Antoni G, Oudot-Mellakh T, Dimitromanolakis A, Germain M, Cohen W, Wells P, et al. Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels. BMC Med Genet. 2011;12:102.PubMedCrossRef Antoni G, Oudot-Mellakh T, Dimitromanolakis A, Germain M, Cohen W, Wells P, et al. Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels. BMC Med Genet. 2011;12:102.PubMedCrossRef
49.
go back to reference Smith NL, Chen MH, Dehghan A, Strachan DP, Basu S, Soranzo N, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation. 2010;121:1382–92.PubMedCrossRef Smith NL, Chen MH, Dehghan A, Strachan DP, Basu S, Soranzo N, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation. 2010;121:1382–92.PubMedCrossRef
50.
go back to reference van Loon JE, Leebeek FW, Deckers JW, Dippel DW, Poldermans D, Strachan DP, et al. Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von Willebrand factor concentration and cardiovascular risk. Circ Cardiovasc Genet. 2010;3:507–12.PubMedCrossRef van Loon JE, Leebeek FW, Deckers JW, Dippel DW, Poldermans D, Strachan DP, et al. Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von Willebrand factor concentration and cardiovascular risk. Circ Cardiovasc Genet. 2010;3:507–12.PubMedCrossRef
51.
go back to reference Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995;345:152–5.PubMedCrossRef Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995;345:152–5.PubMedCrossRef
52.
go back to reference Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Tracy RP, Aleksic N, et al. Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med. 2002;113:636–42.PubMedCrossRef Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Tracy RP, Aleksic N, et al. Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med. 2002;113:636–42.PubMedCrossRef
53.
go back to reference Takahashi M, Yamashita A, Moriguchi-Goto S, Marutsuka K, Sato Y, Yamamoto H, et al. Critical role of von Willebrand factor and platelet interaction in venous thromboembolism. Histol Histopathol. 2009;24:1391–8.PubMed Takahashi M, Yamashita A, Moriguchi-Goto S, Marutsuka K, Sato Y, Yamamoto H, et al. Critical role of von Willebrand factor and platelet interaction in venous thromboembolism. Histol Histopathol. 2009;24:1391–8.PubMed
54.
go back to reference Chauhan AK, Kisucka J, Lamb CB, Bergmeier W, Wagner DD. von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood. 2007;109:2424–9.PubMedCrossRef Chauhan AK, Kisucka J, Lamb CB, Bergmeier W, Wagner DD. von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. Blood. 2007;109:2424–9.PubMedCrossRef
55.
go back to reference Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Kollnberger M, et al. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011;117:1400–7.PubMedCrossRef Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Kollnberger M, et al. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood. 2011;117:1400–7.PubMedCrossRef
56.
go back to reference Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 2010;107:15880–5.PubMedCrossRef Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 2010;107:15880–5.PubMedCrossRef
57.
go back to reference Fuchs TA, Bhandari AA, Wagner DD. Histones induce rapid and profound thrombocytopenia in mice. Blood. 2011;118:3708–14.PubMedCrossRef Fuchs TA, Bhandari AA, Wagner DD. Histones induce rapid and profound thrombocytopenia in mice. Blood. 2011;118:3708–14.PubMedCrossRef
58.
go back to reference Brill A, Fuchs TA, Savchenko A, Thomas GM, Martinod K, De Meyer SF, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2011 (Epub ahead of print). Brill A, Fuchs TA, Savchenko A, Thomas GM, Martinod K, De Meyer SF, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2011 (Epub ahead of print).
59.
go back to reference Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307:1432–5.PubMedCrossRef Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307:1432–5.PubMedCrossRef
61.
go back to reference Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011;118:3212–21.PubMedCrossRef Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011;118:3212–21.PubMedCrossRef
62.
go back to reference Lenting PJ, Pegon JN, Groot E, de Groot PG. Regulation of von Willebrand factor–platelet interactions. Thromb Haemost. 2010;104:449–55.PubMedCrossRef Lenting PJ, Pegon JN, Groot E, de Groot PG. Regulation of von Willebrand factor–platelet interactions. Thromb Haemost. 2010;104:449–55.PubMedCrossRef
63.
go back to reference De Ceunynck K, Rocha S, Feys HB, De Meyer SF, Uji-i H, Deckmyn H, et al. Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis. J Biol Chem. 2011;286:36361–7.PubMedCrossRef De Ceunynck K, Rocha S, Feys HB, De Meyer SF, Uji-i H, Deckmyn H, et al. Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis. J Biol Chem. 2011;286:36361–7.PubMedCrossRef
64.
go back to reference Schneider SW, Nuschele S, Wixforth A, Gorzelanny C, Alexander-Katz A, Netz RR, et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci U S A. 2007;104:7899–903.PubMedCrossRef Schneider SW, Nuschele S, Wixforth A, Gorzelanny C, Alexander-Katz A, Netz RR, et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci U S A. 2007;104:7899–903.PubMedCrossRef
65.
go back to reference Lenting PJ, Rastegarlari G. ADAMTS-13: double trouble for von Willebrand factor. J Thromb Haemost. 2010;8:2775–7.PubMedCrossRef Lenting PJ, Rastegarlari G. ADAMTS-13: double trouble for von Willebrand factor. J Thromb Haemost. 2010;8:2775–7.PubMedCrossRef
66.
go back to reference Ganderton T, Berndt MC, Chesterman CN, Hogg PJ. Hypothesis for control of von Willebrand factor multimer size by intra-molecular thiol-disulphide exchange. J Thromb Haemost. 2007;5:204–6.PubMedCrossRef Ganderton T, Berndt MC, Chesterman CN, Hogg PJ. Hypothesis for control of von Willebrand factor multimer size by intra-molecular thiol-disulphide exchange. J Thromb Haemost. 2007;5:204–6.PubMedCrossRef
67.
go back to reference Li Y, Choi H, Zhou Z, Nolasco L, Pownall HJ, Voorberg J, et al. Covalent regulation of ULVWF string formation and elongation on endothelial cells under flow conditions. J Thromb Haemost. 2008;6:1135–43.PubMedCrossRef Li Y, Choi H, Zhou Z, Nolasco L, Pownall HJ, Voorberg J, et al. Covalent regulation of ULVWF string formation and elongation on endothelial cells under flow conditions. J Thromb Haemost. 2008;6:1135–43.PubMedCrossRef
68.
go back to reference Yeh HC, Zhou Z, Choi H, Tekeoglu S, May W 3rd, Wang C, et al. Disulfide bond reduction of von Willebrand factor by ADAMTS-13. J Thromb Haemost. 2010;8:2778–88.PubMedCrossRef Yeh HC, Zhou Z, Choi H, Tekeoglu S, May W 3rd, Wang C, et al. Disulfide bond reduction of von Willebrand factor by ADAMTS-13. J Thromb Haemost. 2010;8:2778–88.PubMedCrossRef
69.
go back to reference Fu X, Chen J, Gallagher R, Zheng Y, Chung DW, Lopez JA. Shear stress-induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region. Blood. 2011;118:5283–91.PubMedCrossRef Fu X, Chen J, Gallagher R, Zheng Y, Chung DW, Lopez JA. Shear stress-induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region. Blood. 2011;118:5283–91.PubMedCrossRef
70.
go back to reference Chen J, Fu X, Wang Y, Ling M, McMullen B, Kulman J, et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115:706–12.PubMedCrossRef Chen J, Fu X, Wang Y, Ling M, McMullen B, Kulman J, et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115:706–12.PubMedCrossRef
71.
go back to reference Lancellotti S, De Filippis V, Pozzi N, Peyvandi F, Palla R, Rocca B, et al. Formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13: A new prothrombotic mechanism in diseases associated with oxidative stress. Free Radic Biol Med. 2010;48:446–56.PubMedCrossRef Lancellotti S, De Filippis V, Pozzi N, Peyvandi F, Palla R, Rocca B, et al. Formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13: A new prothrombotic mechanism in diseases associated with oxidative stress. Free Radic Biol Med. 2010;48:446–56.PubMedCrossRef
72.
go back to reference De Filippis V, Lancellotti S, Maset F, Spolaore B, Pozzi N, Gambaro G, et al. Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure. Biochem J. 2011 (Epub ahead of print). De Filippis V, Lancellotti S, Maset F, Spolaore B, Pozzi N, Gambaro G, et al. Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure. Biochem J. 2011 (Epub ahead of print).
73.
go back to reference Hulstein JJ, de Groot PG, Silence K, Veyradier A, Fijnheer R, Lenting PJ. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood. 2005;106:3035–42.PubMedCrossRef Hulstein JJ, de Groot PG, Silence K, Veyradier A, Fijnheer R, Lenting PJ. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood. 2005;106:3035–42.PubMedCrossRef
74.
go back to reference Hulstein JJ, Lenting PJ, de Laat B, Derksen RH, Fijnheer R, de Groot PG. beta2-Glycoprotein I inhibits von Willebrand factor dependent platelet adhesion and aggregation. Blood. 2007;110:1483–91.PubMedCrossRef Hulstein JJ, Lenting PJ, de Laat B, Derksen RH, Fijnheer R, de Groot PG. beta2-Glycoprotein I inhibits von Willebrand factor dependent platelet adhesion and aggregation. Blood. 2007;110:1483–91.PubMedCrossRef
75.
go back to reference de Laat B, de Groot PG, Derksen RH, Urbanus RT, Mertens K, Rosendaal FR, et al. Association between beta2-glycoprotein I plasma levels and the risk of myocardial infarction in older men. Blood. 2009;114:3656–61.PubMedCrossRef de Laat B, de Groot PG, Derksen RH, Urbanus RT, Mertens K, Rosendaal FR, et al. Association between beta2-glycoprotein I plasma levels and the risk of myocardial infarction in older men. Blood. 2009;114:3656–61.PubMedCrossRef
76.
go back to reference De Meyer SF, Stoll G, Wagner DD and Kleinschnitz C. von Willebrand factor: an emerging target in stroke therapy. Stroke. 2011 (Epub ahead of print). De Meyer SF, Stoll G, Wagner DD and Kleinschnitz C. von Willebrand factor: an emerging target in stroke therapy. Stroke. 2011 (Epub ahead of print).
77.
go back to reference Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009;113:3600–3.PubMedCrossRef Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009;113:3600–3.PubMedCrossRef
78.
go back to reference De Meyer SF, Schwarz T, Deckmyn H, Denis CV, Nieswandt B, Stoll G, et al. Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, but not to glycoprotein IIb/IIIa, contributes to ischemic stroke in mice—brief report. Arterioscler Thromb Vasc Biol. 2010;30:1949–51.PubMedCrossRef De Meyer SF, Schwarz T, Deckmyn H, Denis CV, Nieswandt B, Stoll G, et al. Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, but not to glycoprotein IIb/IIIa, contributes to ischemic stroke in mice—brief report. Arterioscler Thromb Vasc Biol. 2010;30:1949–51.PubMedCrossRef
79.
go back to reference Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, et al. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest. 2011;121:593–603.PubMedCrossRef Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, et al. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest. 2011;121:593–603.PubMedCrossRef
Metadata
Title
von Willebrand factor: at the crossroads of bleeding and thrombosis
Authors
Cécile V. Denis
Peter J. Lenting
Publication date
01-04-2012
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 4/2012
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-012-1041-x

Other articles of this Issue 4/2012

International Journal of Hematology 4/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine