Thromb Haemost 2007; 98(01): 55-62
DOI: 10.1160/TH07-04-0279
Anniversary Issue Contribution
Schattauer GmbH

Von Willebrand factor: Looking back and looking forward

Zaverio M. Ruggeri
1   Roon Research Center for Arteriosclerosis and Thrombosis, Division of Blood Cell and Vascular Biology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
› Author Affiliations
Further Information

Correspondence to:

Zaverio M. Ruggeri, MD
The Scripps Research Institute
MEM-175
10550 N. Torrey Pines Road
La Jolla, CA 92037, USA
Phone: +1 858 7848950   
Fax: +1 858 7842026   

Publication History

Received 16 April 2007

Accepted 11 May 2007

Publication Date:
29 November 2017 (online)

 

Summary

Looking back at the last thirty years of studies on von Willebrand factor is a lesson on the importance of combining clinical observations with basic research. Most of what we know today originates from the perceptive evaluation of patients with congenital disorders of haemostasis such as haemophilia and von Willebrand disease. Understanding the causes of these diseases was akin to the current approach of using mutagenesis in animal models to get insights into the function of specific gene products. The information generated to date has been detailed and comprehensive, but looking into the future one sees that much remains to be done to understand how the role of von Willebrand factor and its primary platelet receptor, glycoprotein Ib, is integrated into the complex responses to vascular injury. Many challenges remain, along with the hope of translating the knowledge acquired into new and efficacious treatments for arterial thrombosis.


#

 


#
  • References

  • 1 Pool JG, Gershgold EJ, Pappenhagen AR. High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate. Nature 1964; 203: 312.
  • 2 Pool JG, Shannon AE. Production of high-potency concentrates of antihemophilic globulin in a closedbag system. N Engl J Med 1965; 273: 1443-1447.
  • 3 Denson KW, Biggs R, Mannucci PM. An investigation of three patients with Christmas disease due to an abnormal type of factor IX. J Clin Pathol 1968; 21: 160-165.
  • 4 Zimmerman TS, Ratnoff OD. Powell AE. Immunologic differentiation of classic hemophilia (Factor VIII deficiency) and von Willebrand’s disease. With observations on combined deficiencies of antihemophilic factor and proaccelerin (Factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest 1971; 50: 244-254.
  • 5 Weiss HJ, Hoyer LW. von Willebrand factor: Dissociation from antihemophilic factor procoagulant activity. Science 1973; 182: 1149-1151.
  • 6 Nilsson IM, Cronberg S. A severe haemorrhagic disorder with prolonged bleeding time due to a plasma defect but with normal factor VIII. Acta Med Scand 1968; 184: 181-186.
  • 7 Holmberg L, Nilsson IM. Haemophilia A and von Willebrand’s disease in a Swedish family. Acta Paediatr Scand 1972; 61: 517-525.
  • 8 Holmberg L, Nilsson IM. Two genetic variants of von Willebrand’s disease. N Engl J Med 1973; 288: 595-598.
  • 9 Larrieu MJ, Caen JP, Meyer D. et al. Congenital bleeding disorders with long bleeding time and normal platelet count. II. von Willebrand’s disease (report of 37 patients). Am J Med 1968; 45: 354-372.
  • 10 Meyer D, Lavergne JM, Larrieu MJ. et al. Crossreacting material in congenital Factor VIII deficiencies (Hemophilia A and von Willebrand’s disease). Thromb Res 1972; 1: 183-195.
  • 11 Meyer D, Jenkins CSP, Dreyfus M. et al. Experimental model for von Willebrand’s disease. Nature 1973; 243: 293-294.
  • 12 Zimmerman TS, Ratnoff OD. Littell AS. Detection of carriers of classic hemophilia using an immunologic assay for antihemophilic factor (Factor VIII). J Clin Invest 1971; 50: 255-258.
  • 13 Mannucci PM, Ruggeri ZM, Gagnatelli G. Nervous regulation of factor-VIII levels in man. Br J Haematol 1971; 20: 195-207.
  • 14 Mannucci PM, Ruggeri ZM, Pareti FI. et al. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; I: 869-872.
  • 15 Nilsson IM, Holmberg L, Aberg M. et al. The release of plasminogen activator and factor VIII after injection of DDAVP in healthy volunteers and in patients with von Willebrand’s disease. Scand J Haematol 1980; 24: 351-359.
  • 16 Holmberg L, Nilsson IM, Borge L. et al. Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand’s disease. N Engl J Med 1983; 309: 816-821.
  • 17 Nurden AT, Caen JP. An abnormal glycoprotein pattern in three cases of Glanzmann’s thrombasthenia. Br J Haematol 1974; 28: 253-260.
  • 18 Nurden AT, Caen JP. Specific roles for platelet surface glycoproteins in platelet function. Nature 1975; 255: 720-722.
  • 19 Caen JP, Nurden AT, Jeanneau C. et al. Bernard- Soulier syndrome: A new platelet glycoprotein abnormality. Its relationship with platelet adhesion to subendothelium and with the factor VIII von Willebrand protein. J Lab Clin Med 1976; 87: 586-596.
  • 20 Phillips DR, Agin PP. Platelet membrane defects in Glanzmann’s thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 1977; 60: 535-545.
  • 21 Baumgartner HR. The role of blood flow in platelet adhesion, fibrin deposition and formation of mural thrombi. Microvasc Res 1973; 5: 167-179.
  • 22 Glover CJ, McIntire LV, Leverett LB. et al. Effect of shear stress on clot structure formation. Transactions - American Society for Artificial Internal Organs 1974; XX: 463-468.
  • 23 Brown CH, Leverett LB, Lewis CN. et al. Morphological, biochemical and functional changes in human platelets subjected to shear stress. J Lab Clin Med 1975; 86: 462-471.
  • 24 Turitto VT, Baumgartner HR. Effect of physical factors on platelet adherence to subendothelium. Thromb Diath Haemorrh 1974; 60 Suppl 17-24.
  • 25 Tschopp TB, Weiss HJ, Baumgartner HR. Decreased adhesion of platelets to subendothelium in von Willebrand’s disease. J Lab Clin Med 1974; 83: 296-300.
  • 26 Weiss HJ, Tschopp TB, Baumgartner HR. et al. Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium. Further implications on the role of the von Willebrand factor in hemostasis. Am J Med 1974; 57: 920-925.
  • 27 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate-dependent decrease of adhesion in von Willebrand’s disease and the Bernard-Soulier syndrome. J Lab Clin Med 1978; 92: 750-764.
  • 28 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII/von Willebrand factor bound to the subendothelium. Nature 1979; 279: 636-638.
  • 29 Zimmerman TS, Fulcher CA. Factor VIII procoagulant protein. Clin Haematol 1985; 14: 343-358.
  • 30 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325.
  • 31 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of Factor VIII/von Willebrand factor. Blood 1981; 57: 1140-1143.
  • 32 Ruggeri ZM. Type IIB von Willebrand disease: a paradox explains how von Willebrand works. J Thromb Haemost 2004; 2: 2-6.
  • 33 Ruggeri ZM, Pareti FI, Mannucci PM. et al. Heightened interaction between platelets and Factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051.
  • 34 Ginsburg D, Handin RI, Bonthron DT. et al. Human von Willebrand factor (vWF): Isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 1985; 228: 1401-1406.
  • 35 Sadler JE, Shelton-Inloes BB, Sorace JM. et al. Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci 1985; 82: 6394-6398.
  • 36 Lynch DC, Zimmerman TS, Collins CJ. et al. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell 1985; 41: 49-56.
  • 37 Titani K, Kumar S, Takio K. et al. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-3184.
  • 38 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells: identification of a large precursor polypeptide chain. J Biol Chem 1983; 258: 2065-2067.
  • 39 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol 1984; 99: 2123-2130.
  • 40 Sporn LA, Chavin SI, Marder VJ. et al. Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest 1985; 76: 1102-1106.
  • 41 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-190.
  • 42 Moake JL, Rudy CK, Troll JH. et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982; 307: 1432-1435.
  • 43 Dent JA, Berkowitz SD, Ware J. et al. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci USA 1990; 87: 6306-6310.
  • 44 Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88: 774-782.
  • 45 Levy GG, Nichols WC, Lian EC. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-494.
  • 46 Furlan M, Robles R, Lammle 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: 4223-4234.
  • 47 Montgomery RR, Zimmerman TS. von Willebrand’s disease antigen II: A new plasma and platelet antigen deficient in severe von Willebrand’s disease. J Clin Invest 1978; 61: 1498-1507.
  • 48 Fay PJ, Kawai Y, Wagner DD. et al. Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II. Science 1986; 232: 995-998.
  • 49 Tangelder GJ, Slaaf DW, Arts T. et al. Wall shear rate in arterioles in vivo: least estimates from platelet velocity profiles. AmJPhysiol 1988; 254: H1059-H1064.
  • 50 Mailhac A, Badimon JJ, Fallon JT. et al. Effect of an eccentric severe stenosis on fibrin(ogen) deposition on severely damaged vessel wall in arterial thrombosis. Relative contribution of fibrin(ogen) and platelets. Circulation 1994; 90: 988-996.
  • 51 Siegel JM, Markou CP, Ku DN. et al. A scaling law for wall shear rate through an arterial stenosis. J Biomech Eng 1994; 116: 446-451.
  • 52 Bluestein D, Niu L, Schoephoerster RT. et al. Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus. Ann Biomed Eng 1997; 25: 344-356.
  • 53 Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-666.
  • 54 Konstantinides S, Ware J, Marchese P. et al. Distinct antithrombotic consequences of platelet glycoprotein Iba and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost 2006; 4: 2014-2021.
  • 55 Andrews RK, Gardiner EE, Shen Y. et al. Glycoprotein Ib-IX-V. Int J Biochem Cell Biol 2003; 35: 170-1174.
  • 56 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 289-297.
  • 57 Stel HV, Sakariassen KS, de Groot PG. et al. Von Willebrand factor in the vessel wall mediates platelet adherence. Blood 1985; 65: 85-90.
  • 58 Turitto VT, Weiss HJ, Zimmerman TS. et al. Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion. Blood 1985; 65: 823-831.
  • 59 Houdijk WPM, de Groot PG, Nievelstein PFEM. et al. Subendothelial proteins and platelet adhesion. Arteriosclerosis 1986; 6: 24-33.
  • 60 Bowie EJ, Solberg Jr, LA, Fass DN. et al. Transplantation of normal bone marrow into a pig with severe von Willebrand’s disease. J Clin Invest 1986; 78: 26-30.
  • 61 Farndale RW, Sixma JJ, Barnes MJ. et al. The role of collagen in thrombosis and hemostasis. J Thromb Haemost 2004; 2: 561-573.
  • 62 Sixma JJ, van Zanten GH, Saelman EU. et al. Platelet adhesion to collagen. Thromb Haemost 1995; 74: 454-459.
  • 63 Rand JH, Glanville RW, Wu X-X. et al. The significance of subendothelial von Willebrand factor. Thromb Haemost 1997; 78: 445-450.
  • 64 Mazzucato M, Spessotto P, Masotti A. et al. Identification of domains responsible for von Willebrand factor type VI collagen interaction mediating platelet adhesion under high flow. J Biol Chem 1999; 274: 3033-3041.
  • 65 vander Plas RM, Gomes L, Marquart JA. et al. Binding of von Willebrand factor to collagen type III: Role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains. Thromb Haemost 2000; 84: 1005-1111.
  • 66 Bonnefoy A, Romijn RA, Vander voort PA. et al. von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen. J Thromb Haemost 2006; 4: 2151-2161.
  • 67 Ruggeri ZM. Von Willebrand factor. Curr Opin Hematol 2003; 10: 142-149.
  • 68 Pareti FI, Fujimura Y, Dent JA. et al. Isolation and characterization of a collagen binding domain in human von Willebrand factor. J Biol Chem 1986; 261: 15310-15315.
  • 69 Pareti FI, Niiya K, McPherson JM. et al. Isolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen Types I and III. J Biol Chem 1987; 262: 13835-13841.
  • 70 Roth GJ, Titani K, Hoyer LW. et al. Localization of binding sites within human von Willebrand factor for monomeric Type III collagen. Biochemistry 1986; 25: 8357-8361.
  • 71 Hoylaerts MF, Yamamoto H, Nuyts K. et al. von Willebrand factor binds to native collagen VI primarily via its A1 domain. Biochem J 1997; 324: 185-191.
  • 72 Colombatti A, Bonaldo P. The superfamily of proteins with von Willebrand factor type A-like domains: One theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms. Blood 1991; 77: 2305-2315.
  • 73 Cruz MA, Yuan H, Lee JR. et al. Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides. J Biol Chem 1995; 270: 10822-10827. Erratum in: J Biol Chem. 1995; 270: 19668.
  • 74 Lankhof H, van Hoeij M, Schiphorst ME. et al. A3 domain is essential for interaction of von Willebrand factor with collagen type III. Thromb Haemost 1996; 75: 950-958.
  • 75 Romijn RA, Westein E, Bouma B. et al. Mapping the collagen-binding site in the von Willebrand factor- A3 domain. J Biol Chem 2003; 278: 15035-15039.
  • 76 Nishida N, Sumikawa H, Sakakura M. et al. Collagen- binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment. Nat Struct Biol 2003; 10: 53-58.
  • 77 Lisman T, Raynal N, Groeneveld D. et al. A single high-affinity binding site for von Willebrand Factor in collagen III, identified using synthetic triple-helical peptides. Blood. 2006 epub ahead of print.
  • 78 Santoro SA. Preferential binding of high molecular weight forms of von Willebrand factor to fibrillar collagen. Biochim Biophys Acta 1983; 756: 123-126.
  • 79 Wu D, Vanhoorelbeke K, Cauwenberghs N. et al. Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 2002; 99: 3623-3628.
  • 80 Ribba AS, Loisel I, Lavergne JM. 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. Thromb Haemost 2001; 86: 848-854.
  • 81 Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: A 2004 update. Semin Hematol 2005; 42: 15-28.
  • 82 Denis C, Baruch D, Kielty CM. et al. Localization on von Willebrand factor binding domains to endothelial extracellular matrix and to type VI collagen. Arterioscler Thromb Vasc Biol 1993; 13: 398-406.
  • 83 Fujimura Y, Titani K, Holland LZ. et al. A heparinbinding domain of human von Willebrand factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728. J Biol Chem 1987; 262: 1734-1739.
  • 84 Mohri H, Yoshioka A, Zimmerman TS. et al. Isolation of the von Willebrand factor domain interacting with platelet glycoprotein Ib, heparin, and collagen, and characterization of its three distinct functional sites. J Biol Chem 1989; 264: 17361-17367.
  • 85 Sobel M, Soler DF, Kermode JC. et al. Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. J Biol Chem 1992; 267: 8857-8862.
  • 86 Fretto LJ, Fowler WE, McCaslin DR. et al. Substructure of human von Willebrand factor. Proteolysis by V8 and characterization of two functional domains. J Biol Chem 1986; 261: 15679-15689.
  • 87 Guidetti GF, Bartolini B, Bernardi B. et al. Binding of von Willebrand factor to the small proteoglycan decorin. FEBS Lett 2004; 574: 95-100.
  • 88 Roberts DD, Williams SB, Gralnick HR. et al. von Willebrand factor binds specifically to sulfated glycolipids. J Biol Chem 1986; 261: 3306-3309.
  • 89 Data RE, Williams SB, Roberts DD. et al. Platelets adhere to sulfatides by von Willebrand factor dependent and independent mechanisms. Thromb Haemost 1991; 65: 581-587.
  • 90 Christophe O, Obert B, Meyer D. et al. The binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein Ib, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673. Blood 1991; 78: 2310-2317.
  • 91 Andrews RJ, Booth WJ, Bendall LJ. et al. The amino acid sequence glutamine-628 to valine-646 within the A1 repeat domain mediates binding of von Willebrand factor to bovine brain sulfatides and equine tendon collagen. Platelets 1995; 6: 245-251.
  • 92 Borthakur G, Cruz MA, Dong JF. et al. Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood. J Thromb Haemost 2003; 1: 1288-1295.
  • 93 Sobel M, McNeill PM, Carlson PL. et al. Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo. J Clin Invest 1991; 87: 1787-1793.
  • 94 Hada M, Kaminski M, Bockenstedt P. et al. Covalent crosslinking of von Willebrand Factor to fibrin. Blood 1986; 68: 95-101.
  • 95 Ribes JA, Francis CW. Multimer size dependence of von Willebrand factor binding to crosslinked or noncrosslinked fibrin. Blood 1990; 75: 1460-1465.
  • 96 Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8: 1227-1234.
  • 97 Savage B, Sixma JJ, Ruggeri ZM. Functional self-association of von Willebrand factor during platelet adhesion under flow. Proc Natl Acad Sci USA 2002; 99: 425-430.
  • 98 Arya M, Anvari B, Romo GM. et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib- IX complex: studies using optical tweezers. Blood 2002; 99: 3971-3977.
  • 99 Shankaran H, Alexandridis P, Neelamegham S. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension. Blood 2003; 101: 2637-2645.
  • 100 Goto S, Salomon DR, Ikeda Y. et al. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 1995; 270: 23352-23361.
  • 101 Ulrichts H, Vanhoorelbeke K, Girma JP. et al. The von Willebrand factor self-association is modulated by a multiple domain interaction. J Thromb Haemost 2005; 3: 552-561.
  • 102 Siediecki CA, Lestini BJ, Kottke-Marchant K. et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand Factor. Blood 1996; 88: 2939-2950.
  • 103 Celikel R, Ruggeri ZM, Varughese KI. von Willebrand factor conformation and adhesive function is modulated by an internalized water molecule. Nat Struct Biol 2000; 7: 881-884.
  • 104 Hulstein JJ, de Groot PG, Silence K. et al. 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: 3035-3042.
  • 105 Huizinga EG, Tsuji S, Romijn RA. et al. Structures of glycoprotein Ib? and its complex with von Willebrand factor A1 domain. Science 2002; 297: 1176-1179.
  • 106 Dumas JJ, Kumar R, McDonagh T. et al. Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ib? complex reveals conformation differences with a complex bearing von Willebrand disease mutations. J Biol Chem 2004; 279: 23327-22334.
  • 107 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110.
  • 108 Lopez-Fernandez MF, Ginsberg MH, Ruggeri ZM. et al. Multimeric structure of platelet factor VIII/ von Willebrand factor. The presence of larger multimers and their reassociation with thrombinstimulated platelets. Blood 1982; 60: 1132-1138.
  • 109 Dong J-F, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultra-large von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
  • 110 Zimmerman TS, Dent JA, Ruggeri ZM. et al. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (Types IIC, IID and IIE). J Clin Invest 1986; 77: 947-951.
  • 111 Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347: 589-600.
  • 112 Donadelli R, Orje JN, Capoferri C. et al. Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS-13 in flowing blood. Blood 2006; 107: 1943-1950.
  • 113 Chauhan AK, Motto DG, Lamb CB. et al. Systemic antithrombotic effects of ADAMTS13. J Exp Med 2006; 203: 767-776.
  • 114 Ruggeri ZM, Dent JA, Saldivar E. Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. Blood 1999; 94: 172-178.
  • 115 Ruggeri ZM, Orje JN, Habermann R. et al. Activation- independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-1910.
  • 116 Chion CK, Doggen CJ, Crawley JT. et al. ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men. Blood 2007; 109: 1998-2000.
  • 117 Ruggeri ZM, Bader R, De Marco L. Glanzmann thrombasthenia: Deficient binding of von Willebrand factor to thrombin-stimulated platelets. Proc Natl Acad Sci 1982; 79: 6038-6041.
  • 118 Ruggeri ZM, De Marco L, Gatti L. et al. Platelets have more than one binding site for von Willebrand factor. J Clin Invest 1983; 72: 1-12.
  • 119 Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol 2005; 17: 509-516.
  • 120 Coller BS, Cheresh DA, Asch E. et al. Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel. Blood 1991; 77: 75-83.
  • 121 Dejana E, Lampugnani MG, Giorgi M. et al. von Willebrand factor promotes endothelial cell adhesion via an arg-gly-asp-dependent mechanism. J Cell Biol 1989; 109: 367-375.
  • 122 Romo GM, Dong JF, Schade AJ. et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190: 803-814.
  • 123 Simon DI, Chen Z, Xu H. et al. Platelet glycoprotein Ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
  • 124 Wagner DD, Burger PC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2003; 23: 2131-2137.
  • 125 Coller BS, Peerschke EI, Scudder LE. et al. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic- like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-338.
  • 126 Ginsberg MH, Forsyth J, Lightsey A. et al. Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets. J Clin Invest 1983; 71: 619-624.
  • 127 Andre P, Prasad KS, Denis CV. et al. CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism. Nat Med 2002; 8: 247-252.
  • 128 Fujimura Y, Titani K, Holland LZ. et al. von Willebrand factor. A reduced and alkylated 52/48 kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem 1986; 261: 381-385.
  • 129 Shelton-Inloes BB, Titani K, Sadler JE. cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms. Biochemistry 1986; 25: 3164-3171.
  • 130 Doggett TA, Girdhar G, Lawshe A. et al. Selectinlike kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIbalpha-vWF tether bond. Biophys J 2002; 83: 194-205.
  • 131 André P, Denis CV, Ware J. et al. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-3328.
  • 132 Frenette PS, Johnson RC, Hynes RO. et al. Platelets roll on stimulated endothelium in vivo: An interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
  • 133 Plow EF, McEver RP, Coller BS. et al. Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombinstimulated human platelets. Blood 1985; 66: 724-727.
  • 134 Plow EF, Pierschbacher MD, Ruoslahti E. et al. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci 1985; 82: 8057-8061.
  • 135 Clemetson KJ, Clemetson JM. Platelet collagen receptors. Thromb Haemost 2001; 86: 189-197.
  • 136 Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor?. Blood 2003; 102: 449-461.
  • 137 Nesbitt WS, Kulkarni S, Giuliano S. et al. Distinct glycoprotein Ib/V/IX and integrin ?IIb?3-dependent calcium signals cooperatively regulate platelet adhesion under flow. J Biol Chem 2002; 277: 2965-2972.
  • 138 Mazzucato M, Pradella P, Cozzi MR. et al. Sequential cytoplasmic calcium signals in a two-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor. Blood 2002; 100: 2793-2800.
  • 139 Mazzucato M, Cozzi MR, Pradella P. et al. Distinct roles of ADP receptors in von Willebrand factor-mediated platelet signaling and activation under high flow. Blood 2004; 104: 3221-3227.
  • 140 Kasirer-Friede A, Cozzi MR, Mazzucato M. et al. Signaling through GP Ib-IX-V activates ?IIb?3 independently of other receptors. Blood 2004; 103: 3403-3411.
  • 141 Kasirer-Friede A, Moran PB, Nagrampa-Orje J. et al. ADAP is required for normal {alpha}IIb{beta}3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2006 Epub ahead of print.
  • 142 Jurk K, Clemetson KJ, de Groot PG. et al. Thrombospondin- 1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. FASEB J 2003; 17: 1490-1492.
  • 143 Baglia FA, Shrimpton CN, Emsley J. et al. Factor XI interacts with leucine-rich repeats of glycoprotein Ib? on the activated platelet. J Biol Chem 2004; 279: 49323-49329.
  • 144 Celikel R, McClintock RA, Roberts JR. et al. Modulation of α-thrombin function by distinct interactions with platelet glycoprotein Ibα. Science 2003; 301: 218-221.
  • 145 Dumas JJ, Kumar R, Seehra J. et al. Crystal structure of the GpIbα-thrombin complex essential for platelet aggregation. Science 2003; 301: 222-226.
  • 146 Dormann D, Clemetson KJ, Kehrel BE. The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. Blood 2000; 96: 2469-2478.
  • 147 Kisucka J, Butterfield CE, Duda DG. et al. Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci USA 2006; 103: 855-860.

Correspondence to:

Zaverio M. Ruggeri, MD
The Scripps Research Institute
MEM-175
10550 N. Torrey Pines Road
La Jolla, CA 92037, USA
Phone: +1 858 7848950   
Fax: +1 858 7842026   

  • References

  • 1 Pool JG, Gershgold EJ, Pappenhagen AR. High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate. Nature 1964; 203: 312.
  • 2 Pool JG, Shannon AE. Production of high-potency concentrates of antihemophilic globulin in a closedbag system. N Engl J Med 1965; 273: 1443-1447.
  • 3 Denson KW, Biggs R, Mannucci PM. An investigation of three patients with Christmas disease due to an abnormal type of factor IX. J Clin Pathol 1968; 21: 160-165.
  • 4 Zimmerman TS, Ratnoff OD. Powell AE. Immunologic differentiation of classic hemophilia (Factor VIII deficiency) and von Willebrand’s disease. With observations on combined deficiencies of antihemophilic factor and proaccelerin (Factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest 1971; 50: 244-254.
  • 5 Weiss HJ, Hoyer LW. von Willebrand factor: Dissociation from antihemophilic factor procoagulant activity. Science 1973; 182: 1149-1151.
  • 6 Nilsson IM, Cronberg S. A severe haemorrhagic disorder with prolonged bleeding time due to a plasma defect but with normal factor VIII. Acta Med Scand 1968; 184: 181-186.
  • 7 Holmberg L, Nilsson IM. Haemophilia A and von Willebrand’s disease in a Swedish family. Acta Paediatr Scand 1972; 61: 517-525.
  • 8 Holmberg L, Nilsson IM. Two genetic variants of von Willebrand’s disease. N Engl J Med 1973; 288: 595-598.
  • 9 Larrieu MJ, Caen JP, Meyer D. et al. Congenital bleeding disorders with long bleeding time and normal platelet count. II. von Willebrand’s disease (report of 37 patients). Am J Med 1968; 45: 354-372.
  • 10 Meyer D, Lavergne JM, Larrieu MJ. et al. Crossreacting material in congenital Factor VIII deficiencies (Hemophilia A and von Willebrand’s disease). Thromb Res 1972; 1: 183-195.
  • 11 Meyer D, Jenkins CSP, Dreyfus M. et al. Experimental model for von Willebrand’s disease. Nature 1973; 243: 293-294.
  • 12 Zimmerman TS, Ratnoff OD. Littell AS. Detection of carriers of classic hemophilia using an immunologic assay for antihemophilic factor (Factor VIII). J Clin Invest 1971; 50: 255-258.
  • 13 Mannucci PM, Ruggeri ZM, Gagnatelli G. Nervous regulation of factor-VIII levels in man. Br J Haematol 1971; 20: 195-207.
  • 14 Mannucci PM, Ruggeri ZM, Pareti FI. et al. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; I: 869-872.
  • 15 Nilsson IM, Holmberg L, Aberg M. et al. The release of plasminogen activator and factor VIII after injection of DDAVP in healthy volunteers and in patients with von Willebrand’s disease. Scand J Haematol 1980; 24: 351-359.
  • 16 Holmberg L, Nilsson IM, Borge L. et al. Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand’s disease. N Engl J Med 1983; 309: 816-821.
  • 17 Nurden AT, Caen JP. An abnormal glycoprotein pattern in three cases of Glanzmann’s thrombasthenia. Br J Haematol 1974; 28: 253-260.
  • 18 Nurden AT, Caen JP. Specific roles for platelet surface glycoproteins in platelet function. Nature 1975; 255: 720-722.
  • 19 Caen JP, Nurden AT, Jeanneau C. et al. Bernard- Soulier syndrome: A new platelet glycoprotein abnormality. Its relationship with platelet adhesion to subendothelium and with the factor VIII von Willebrand protein. J Lab Clin Med 1976; 87: 586-596.
  • 20 Phillips DR, Agin PP. Platelet membrane defects in Glanzmann’s thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 1977; 60: 535-545.
  • 21 Baumgartner HR. The role of blood flow in platelet adhesion, fibrin deposition and formation of mural thrombi. Microvasc Res 1973; 5: 167-179.
  • 22 Glover CJ, McIntire LV, Leverett LB. et al. Effect of shear stress on clot structure formation. Transactions - American Society for Artificial Internal Organs 1974; XX: 463-468.
  • 23 Brown CH, Leverett LB, Lewis CN. et al. Morphological, biochemical and functional changes in human platelets subjected to shear stress. J Lab Clin Med 1975; 86: 462-471.
  • 24 Turitto VT, Baumgartner HR. Effect of physical factors on platelet adherence to subendothelium. Thromb Diath Haemorrh 1974; 60 Suppl 17-24.
  • 25 Tschopp TB, Weiss HJ, Baumgartner HR. Decreased adhesion of platelets to subendothelium in von Willebrand’s disease. J Lab Clin Med 1974; 83: 296-300.
  • 26 Weiss HJ, Tschopp TB, Baumgartner HR. et al. Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium. Further implications on the role of the von Willebrand factor in hemostasis. Am J Med 1974; 57: 920-925.
  • 27 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate-dependent decrease of adhesion in von Willebrand’s disease and the Bernard-Soulier syndrome. J Lab Clin Med 1978; 92: 750-764.
  • 28 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII/von Willebrand factor bound to the subendothelium. Nature 1979; 279: 636-638.
  • 29 Zimmerman TS, Fulcher CA. Factor VIII procoagulant protein. Clin Haematol 1985; 14: 343-358.
  • 30 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325.
  • 31 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of Factor VIII/von Willebrand factor. Blood 1981; 57: 1140-1143.
  • 32 Ruggeri ZM. Type IIB von Willebrand disease: a paradox explains how von Willebrand works. J Thromb Haemost 2004; 2: 2-6.
  • 33 Ruggeri ZM, Pareti FI, Mannucci PM. et al. Heightened interaction between platelets and Factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051.
  • 34 Ginsburg D, Handin RI, Bonthron DT. et al. Human von Willebrand factor (vWF): Isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 1985; 228: 1401-1406.
  • 35 Sadler JE, Shelton-Inloes BB, Sorace JM. et al. Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci 1985; 82: 6394-6398.
  • 36 Lynch DC, Zimmerman TS, Collins CJ. et al. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell 1985; 41: 49-56.
  • 37 Titani K, Kumar S, Takio K. et al. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-3184.
  • 38 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells: identification of a large precursor polypeptide chain. J Biol Chem 1983; 258: 2065-2067.
  • 39 Wagner DD, Marder VJ. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol 1984; 99: 2123-2130.
  • 40 Sporn LA, Chavin SI, Marder VJ. et al. Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest 1985; 76: 1102-1106.
  • 41 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-190.
  • 42 Moake JL, Rudy CK, Troll JH. et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982; 307: 1432-1435.
  • 43 Dent JA, Berkowitz SD, Ware J. et al. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci USA 1990; 87: 6306-6310.
  • 44 Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88: 774-782.
  • 45 Levy GG, Nichols WC, Lian EC. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-494.
  • 46 Furlan M, Robles R, Lammle 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: 4223-4234.
  • 47 Montgomery RR, Zimmerman TS. von Willebrand’s disease antigen II: A new plasma and platelet antigen deficient in severe von Willebrand’s disease. J Clin Invest 1978; 61: 1498-1507.
  • 48 Fay PJ, Kawai Y, Wagner DD. et al. Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II. Science 1986; 232: 995-998.
  • 49 Tangelder GJ, Slaaf DW, Arts T. et al. Wall shear rate in arterioles in vivo: least estimates from platelet velocity profiles. AmJPhysiol 1988; 254: H1059-H1064.
  • 50 Mailhac A, Badimon JJ, Fallon JT. et al. Effect of an eccentric severe stenosis on fibrin(ogen) deposition on severely damaged vessel wall in arterial thrombosis. Relative contribution of fibrin(ogen) and platelets. Circulation 1994; 90: 988-996.
  • 51 Siegel JM, Markou CP, Ku DN. et al. A scaling law for wall shear rate through an arterial stenosis. J Biomech Eng 1994; 116: 446-451.
  • 52 Bluestein D, Niu L, Schoephoerster RT. et al. Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus. Ann Biomed Eng 1997; 25: 344-356.
  • 53 Savage B, Almus-Jacobs F, Ruggeri ZM. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-666.
  • 54 Konstantinides S, Ware J, Marchese P. et al. Distinct antithrombotic consequences of platelet glycoprotein Iba and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost 2006; 4: 2014-2021.
  • 55 Andrews RK, Gardiner EE, Shen Y. et al. Glycoprotein Ib-IX-V. Int J Biochem Cell Biol 2003; 35: 170-1174.
  • 56 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84: 289-297.
  • 57 Stel HV, Sakariassen KS, de Groot PG. et al. Von Willebrand factor in the vessel wall mediates platelet adherence. Blood 1985; 65: 85-90.
  • 58 Turitto VT, Weiss HJ, Zimmerman TS. et al. Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion. Blood 1985; 65: 823-831.
  • 59 Houdijk WPM, de Groot PG, Nievelstein PFEM. et al. Subendothelial proteins and platelet adhesion. Arteriosclerosis 1986; 6: 24-33.
  • 60 Bowie EJ, Solberg Jr, LA, Fass DN. et al. Transplantation of normal bone marrow into a pig with severe von Willebrand’s disease. J Clin Invest 1986; 78: 26-30.
  • 61 Farndale RW, Sixma JJ, Barnes MJ. et al. The role of collagen in thrombosis and hemostasis. J Thromb Haemost 2004; 2: 561-573.
  • 62 Sixma JJ, van Zanten GH, Saelman EU. et al. Platelet adhesion to collagen. Thromb Haemost 1995; 74: 454-459.
  • 63 Rand JH, Glanville RW, Wu X-X. et al. The significance of subendothelial von Willebrand factor. Thromb Haemost 1997; 78: 445-450.
  • 64 Mazzucato M, Spessotto P, Masotti A. et al. Identification of domains responsible for von Willebrand factor type VI collagen interaction mediating platelet adhesion under high flow. J Biol Chem 1999; 274: 3033-3041.
  • 65 vander Plas RM, Gomes L, Marquart JA. et al. Binding of von Willebrand factor to collagen type III: Role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains. Thromb Haemost 2000; 84: 1005-1111.
  • 66 Bonnefoy A, Romijn RA, Vander voort PA. et al. von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen. J Thromb Haemost 2006; 4: 2151-2161.
  • 67 Ruggeri ZM. Von Willebrand factor. Curr Opin Hematol 2003; 10: 142-149.
  • 68 Pareti FI, Fujimura Y, Dent JA. et al. Isolation and characterization of a collagen binding domain in human von Willebrand factor. J Biol Chem 1986; 261: 15310-15315.
  • 69 Pareti FI, Niiya K, McPherson JM. et al. Isolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen Types I and III. J Biol Chem 1987; 262: 13835-13841.
  • 70 Roth GJ, Titani K, Hoyer LW. et al. Localization of binding sites within human von Willebrand factor for monomeric Type III collagen. Biochemistry 1986; 25: 8357-8361.
  • 71 Hoylaerts MF, Yamamoto H, Nuyts K. et al. von Willebrand factor binds to native collagen VI primarily via its A1 domain. Biochem J 1997; 324: 185-191.
  • 72 Colombatti A, Bonaldo P. The superfamily of proteins with von Willebrand factor type A-like domains: One theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms. Blood 1991; 77: 2305-2315.
  • 73 Cruz MA, Yuan H, Lee JR. et al. Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides. J Biol Chem 1995; 270: 10822-10827. Erratum in: J Biol Chem. 1995; 270: 19668.
  • 74 Lankhof H, van Hoeij M, Schiphorst ME. et al. A3 domain is essential for interaction of von Willebrand factor with collagen type III. Thromb Haemost 1996; 75: 950-958.
  • 75 Romijn RA, Westein E, Bouma B. et al. Mapping the collagen-binding site in the von Willebrand factor- A3 domain. J Biol Chem 2003; 278: 15035-15039.
  • 76 Nishida N, Sumikawa H, Sakakura M. et al. Collagen- binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment. Nat Struct Biol 2003; 10: 53-58.
  • 77 Lisman T, Raynal N, Groeneveld D. et al. A single high-affinity binding site for von Willebrand Factor in collagen III, identified using synthetic triple-helical peptides. Blood. 2006 epub ahead of print.
  • 78 Santoro SA. Preferential binding of high molecular weight forms of von Willebrand factor to fibrillar collagen. Biochim Biophys Acta 1983; 756: 123-126.
  • 79 Wu D, Vanhoorelbeke K, Cauwenberghs N. et al. Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 2002; 99: 3623-3628.
  • 80 Ribba AS, Loisel I, Lavergne JM. 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. Thromb Haemost 2001; 86: 848-854.
  • 81 Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: A 2004 update. Semin Hematol 2005; 42: 15-28.
  • 82 Denis C, Baruch D, Kielty CM. et al. Localization on von Willebrand factor binding domains to endothelial extracellular matrix and to type VI collagen. Arterioscler Thromb Vasc Biol 1993; 13: 398-406.
  • 83 Fujimura Y, Titani K, Holland LZ. et al. A heparinbinding domain of human von Willebrand factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728. J Biol Chem 1987; 262: 1734-1739.
  • 84 Mohri H, Yoshioka A, Zimmerman TS. et al. Isolation of the von Willebrand factor domain interacting with platelet glycoprotein Ib, heparin, and collagen, and characterization of its three distinct functional sites. J Biol Chem 1989; 264: 17361-17367.
  • 85 Sobel M, Soler DF, Kermode JC. et al. Localization and characterization of a heparin binding domain peptide of human von Willebrand factor. J Biol Chem 1992; 267: 8857-8862.
  • 86 Fretto LJ, Fowler WE, McCaslin DR. et al. Substructure of human von Willebrand factor. Proteolysis by V8 and characterization of two functional domains. J Biol Chem 1986; 261: 15679-15689.
  • 87 Guidetti GF, Bartolini B, Bernardi B. et al. Binding of von Willebrand factor to the small proteoglycan decorin. FEBS Lett 2004; 574: 95-100.
  • 88 Roberts DD, Williams SB, Gralnick HR. et al. von Willebrand factor binds specifically to sulfated glycolipids. J Biol Chem 1986; 261: 3306-3309.
  • 89 Data RE, Williams SB, Roberts DD. et al. Platelets adhere to sulfatides by von Willebrand factor dependent and independent mechanisms. Thromb Haemost 1991; 65: 581-587.
  • 90 Christophe O, Obert B, Meyer D. et al. The binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein Ib, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673. Blood 1991; 78: 2310-2317.
  • 91 Andrews RJ, Booth WJ, Bendall LJ. et al. The amino acid sequence glutamine-628 to valine-646 within the A1 repeat domain mediates binding of von Willebrand factor to bovine brain sulfatides and equine tendon collagen. Platelets 1995; 6: 245-251.
  • 92 Borthakur G, Cruz MA, Dong JF. et al. Sulfatides inhibit platelet adhesion to von Willebrand factor in flowing blood. J Thromb Haemost 2003; 1: 1288-1295.
  • 93 Sobel M, McNeill PM, Carlson PL. et al. Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo. J Clin Invest 1991; 87: 1787-1793.
  • 94 Hada M, Kaminski M, Bockenstedt P. et al. Covalent crosslinking of von Willebrand Factor to fibrin. Blood 1986; 68: 95-101.
  • 95 Ribes JA, Francis CW. Multimer size dependence of von Willebrand factor binding to crosslinked or noncrosslinked fibrin. Blood 1990; 75: 1460-1465.
  • 96 Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002; 8: 1227-1234.
  • 97 Savage B, Sixma JJ, Ruggeri ZM. Functional self-association of von Willebrand factor during platelet adhesion under flow. Proc Natl Acad Sci USA 2002; 99: 425-430.
  • 98 Arya M, Anvari B, Romo GM. et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib- IX complex: studies using optical tweezers. Blood 2002; 99: 3971-3977.
  • 99 Shankaran H, Alexandridis P, Neelamegham S. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension. Blood 2003; 101: 2637-2645.
  • 100 Goto S, Salomon DR, Ikeda Y. et al. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 1995; 270: 23352-23361.
  • 101 Ulrichts H, Vanhoorelbeke K, Girma JP. et al. The von Willebrand factor self-association is modulated by a multiple domain interaction. J Thromb Haemost 2005; 3: 552-561.
  • 102 Siediecki CA, Lestini BJ, Kottke-Marchant K. et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand Factor. Blood 1996; 88: 2939-2950.
  • 103 Celikel R, Ruggeri ZM, Varughese KI. von Willebrand factor conformation and adhesive function is modulated by an internalized water molecule. Nat Struct Biol 2000; 7: 881-884.
  • 104 Hulstein JJ, de Groot PG, Silence K. et al. 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: 3035-3042.
  • 105 Huizinga EG, Tsuji S, Romijn RA. et al. Structures of glycoprotein Ib? and its complex with von Willebrand factor A1 domain. Science 2002; 297: 1176-1179.
  • 106 Dumas JJ, Kumar R, McDonagh T. et al. Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ib? complex reveals conformation differences with a complex bearing von Willebrand disease mutations. J Biol Chem 2004; 279: 23327-22334.
  • 107 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110.
  • 108 Lopez-Fernandez MF, Ginsberg MH, Ruggeri ZM. et al. Multimeric structure of platelet factor VIII/ von Willebrand factor. The presence of larger multimers and their reassociation with thrombinstimulated platelets. Blood 1982; 60: 1132-1138.
  • 109 Dong J-F, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultra-large von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
  • 110 Zimmerman TS, Dent JA, Ruggeri ZM. et al. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (Types IIC, IID and IIE). J Clin Invest 1986; 77: 947-951.
  • 111 Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347: 589-600.
  • 112 Donadelli R, Orje JN, Capoferri C. et al. Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS-13 in flowing blood. Blood 2006; 107: 1943-1950.
  • 113 Chauhan AK, Motto DG, Lamb CB. et al. Systemic antithrombotic effects of ADAMTS13. J Exp Med 2006; 203: 767-776.
  • 114 Ruggeri ZM, Dent JA, Saldivar E. Contribution of distinct adhesive interactions to platelet aggregation in flowing blood. Blood 1999; 94: 172-178.
  • 115 Ruggeri ZM, Orje JN, Habermann R. et al. Activation- independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-1910.
  • 116 Chion CK, Doggen CJ, Crawley JT. et al. ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men. Blood 2007; 109: 1998-2000.
  • 117 Ruggeri ZM, Bader R, De Marco L. Glanzmann thrombasthenia: Deficient binding of von Willebrand factor to thrombin-stimulated platelets. Proc Natl Acad Sci 1982; 79: 6038-6041.
  • 118 Ruggeri ZM, De Marco L, Gatti L. et al. Platelets have more than one binding site for von Willebrand factor. J Clin Invest 1983; 72: 1-12.
  • 119 Ginsberg MH, Partridge A, Shattil SJ. Integrin regulation. Curr Opin Cell Biol 2005; 17: 509-516.
  • 120 Coller BS, Cheresh DA, Asch E. et al. Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel. Blood 1991; 77: 75-83.
  • 121 Dejana E, Lampugnani MG, Giorgi M. et al. von Willebrand factor promotes endothelial cell adhesion via an arg-gly-asp-dependent mechanism. J Cell Biol 1989; 109: 367-375.
  • 122 Romo GM, Dong JF, Schade AJ. et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190: 803-814.
  • 123 Simon DI, Chen Z, Xu H. et al. Platelet glycoprotein Ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
  • 124 Wagner DD, Burger PC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2003; 23: 2131-2137.
  • 125 Coller BS, Peerschke EI, Scudder LE. et al. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic- like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-338.
  • 126 Ginsberg MH, Forsyth J, Lightsey A. et al. Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets. J Clin Invest 1983; 71: 619-624.
  • 127 Andre P, Prasad KS, Denis CV. et al. CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism. Nat Med 2002; 8: 247-252.
  • 128 Fujimura Y, Titani K, Holland LZ. et al. von Willebrand factor. A reduced and alkylated 52/48 kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem 1986; 261: 381-385.
  • 129 Shelton-Inloes BB, Titani K, Sadler JE. cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms. Biochemistry 1986; 25: 3164-3171.
  • 130 Doggett TA, Girdhar G, Lawshe A. et al. Selectinlike kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIbalpha-vWF tether bond. Biophys J 2002; 83: 194-205.
  • 131 André P, Denis CV, Ware J. et al. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-3328.
  • 132 Frenette PS, Johnson RC, Hynes RO. et al. Platelets roll on stimulated endothelium in vivo: An interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
  • 133 Plow EF, McEver RP, Coller BS. et al. Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombinstimulated human platelets. Blood 1985; 66: 724-727.
  • 134 Plow EF, Pierschbacher MD, Ruoslahti E. et al. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci 1985; 82: 8057-8061.
  • 135 Clemetson KJ, Clemetson JM. Platelet collagen receptors. Thromb Haemost 2001; 86: 189-197.
  • 136 Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor?. Blood 2003; 102: 449-461.
  • 137 Nesbitt WS, Kulkarni S, Giuliano S. et al. Distinct glycoprotein Ib/V/IX and integrin ?IIb?3-dependent calcium signals cooperatively regulate platelet adhesion under flow. J Biol Chem 2002; 277: 2965-2972.
  • 138 Mazzucato M, Pradella P, Cozzi MR. et al. Sequential cytoplasmic calcium signals in a two-stage platelet activation process induced by the glycoprotein Ibα mechanoreceptor. Blood 2002; 100: 2793-2800.
  • 139 Mazzucato M, Cozzi MR, Pradella P. et al. Distinct roles of ADP receptors in von Willebrand factor-mediated platelet signaling and activation under high flow. Blood 2004; 104: 3221-3227.
  • 140 Kasirer-Friede A, Cozzi MR, Mazzucato M. et al. Signaling through GP Ib-IX-V activates ?IIb?3 independently of other receptors. Blood 2004; 103: 3403-3411.
  • 141 Kasirer-Friede A, Moran PB, Nagrampa-Orje J. et al. ADAP is required for normal {alpha}IIb{beta}3 activation by VWF/GP Ib-IX-V and other agonists. Blood. 2006 Epub ahead of print.
  • 142 Jurk K, Clemetson KJ, de Groot PG. et al. Thrombospondin- 1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. FASEB J 2003; 17: 1490-1492.
  • 143 Baglia FA, Shrimpton CN, Emsley J. et al. Factor XI interacts with leucine-rich repeats of glycoprotein Ib? on the activated platelet. J Biol Chem 2004; 279: 49323-49329.
  • 144 Celikel R, McClintock RA, Roberts JR. et al. Modulation of α-thrombin function by distinct interactions with platelet glycoprotein Ibα. Science 2003; 301: 218-221.
  • 145 Dumas JJ, Kumar R, Seehra J. et al. Crystal structure of the GpIbα-thrombin complex essential for platelet aggregation. Science 2003; 301: 222-226.
  • 146 Dormann D, Clemetson KJ, Kehrel BE. The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. Blood 2000; 96: 2469-2478.
  • 147 Kisucka J, Butterfield CE, Duda DG. et al. Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci USA 2006; 103: 855-860.