Hamostaseologie 2009; 29(01): 32-38
DOI: 10.1055/s-0037-1616936
Original article
Schattauer GmbH

Role of von Willebrand factor in vascular disease

P. Paulinska
1   Department of Clinical Pharmacology, Medical University of Vienna, Austria
,
A. Spiel
1   Department of Clinical Pharmacology, Medical University of Vienna, Austria
,
B. Jilma
1   Department of Clinical Pharmacology, Medical University of Vienna, Austria
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
29. Dezember 2017 (online)

Summary

Plasma levels of von Willebrand factor (VWF) are increased in patients with cardiovascular risk factors. Various studies aimed to elucidate the relation of VWF with thrombo - embolic cardiovascular events, ischaemic stroke as well as with peripheral arterial occlusive disease. In the general population, there is only a weak association between VWF levels and future cardiovascular events or stroke. In contrast, VWF levels are predictive in patients with documented vascular disease. Those patients with increased VWF suffer a higher incidence of major adverse cardiac events including death. The extent of the VWF release and its levels independently predict clinical outcome in patients with acute coronary syndromes. Elevated VWF levels have also been observed in patients with atrial fibrillation compared to controls and predict outcome. This may at least in part be attributable to the association of VWF with underlying cardiovascular risk factors. Hence, VWF correlates with Framingham and CHADS stroke risk stratification score and can be used as a marker in patients with AF. However, VWF is not only a predictor; it also plays a crucial role in thrombogenesis. This fact has made VWF a promising target for research into new antiplatelet therapies that specifically inhibit VWF.

This review focuses on the role of VWF in ACS, ischaemic stroke and peripheral arterial disease and the relevance of therapeutic interventions targeting VWF for ACS patients.

 
  • References

  • 1 Ruggeri ZM, Ware J. Von Willebrand factor. Faseb J 1993; 7: 308-316.
  • 2 Fredrickson BJ, Dong JF, McIntire LV, Lopez JA. Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex. Blood 1998; 92: 3684-3693.
  • 3 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-246.
  • 4 Siedlecki CA, Lestini BJ, Kottke-Marchant KK. et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 1996; 88: 2939-2950.
  • 5 Hollestelle MJ, Thinnes T, Crain K. et al. Tissue distribution of factor VIII gene expression in vivo--a closer look. Thromb Haemost 2001; 86: 855-861.
  • 6 Mannucci PM. Platelet von Willebrand factor in inherited and acquired bleeding disorders. Proc Natl Acad Sci USA 1995; 92: 2428-2432.
  • 7 Blann A. Von Willebrand factor and the endothelium in vascular disease. Br J Biomed Sci 1993; 50: 125-134.
  • 8 Brinkhous KM, Sandberg H, Garris JB. et al. Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs. Proc Natl Acad Sci USA 1985; 82: 8752-8756.
  • 9 Lip GY, Blann A. Von Willebrand factor: a marker of endothelial dysfunction in vascular disorders?. Cardiovasc Res 1997; 34: 255-265.
  • 10 Spiel AO, Gilbert JC, Jilma B. Von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation 2008; 117: 1449-1459.
  • 11 Pinsky DJ, Naka Y, Liao H. et al. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97: 493-500.
  • 12 Paleolog EM, Crossman DC, McVey JH, Pearson JD. Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells. Blood 1990; 75: 688-695.
  • 13 Levine JD, Harlan JM, Harker LA. et al. Thrombin- mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture. Blood 1982; 60: 531-534.
  • 14 Chignard M, Balloy V, Renesto P. Leucocyte elastase- mediated release of von Willebrand factor from cultured endothelial cells. Eur Respir J 1993; 6: 791-796.
  • 15 Jilma B, Pernerstorfer T, Dirnberger E. et al. Effects of histamine and nitric oxide synthase inhibition on plasma levels of von Willebrand factor antigen. J Lab Clin Med 1998; 131: 151-156.
  • 16 Schorer AE, Moldow CF, Rick ME. Interleukin 1 or endotoxin increases the release of von Willebrand factor from human endothelial cells. Br J Haematol 1987; 67: 193-197.
  • 17 Rickles FR, Hoyer LW, Rick ME, Ahr DJ. The effects of epinephrine infusion in patients with von Willebrand’s disease. J Clin Invest 1976; 57: 1618-1625.
  • 18 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; 1: 869-872.
  • 19 Pernerstorfer T, Stohlawetz P, Kapiotis S. et al. Partial inhibition of nitric oxide synthase primes the stimulated pathway of VWF-secretion in man. Atherosclerosis 2000; 148: 43-47.
  • 20 Jilma B, Dirnberger E, Eichler HG. et al. Partial blockade of nitric oxide synthase blunts the exercise- induced increase of von Willebrand factor antigen and of factor VIII in man. Thromb Haemost 1997; 78: 1268-1271.
  • 21 Gallinaro L, Cattini MG, Sztukowska M. et al. A shorter von Willebrand factor survival in 0 blood group subjects explains how AB0 determinants influence plasma von Willebrand factor. Blood 2008; 111: 3540-3545.
  • 22 Kadir RA, Economides DL, Sabin CA. et al. Variations in coagulation factors in women: effects of age, ethnicity, menstrual cycle and combined oral contraceptive. Thromb Haemost 1999; 82: 1456-1461.
  • 23 Blann AD. Plasma von Willebrand factor, thrombosis, and the endothelium: the first 30 years. Thromb Haemost 2006; 95: 49-55.
  • 24 Miura S, Li CQ, Cao Z. et al. Interaction of von Willebrand factor domain A1 with platelet glycoprotein Ibalpha-(1–289). Slow intrinsic binding kinetics mediate rapid platelet adhesion. J Biol Chem 2000; 275: 7539-7546.
  • 25 Bonnefoy A, Yamamoto H, Thys C. et al. Shielding the front-strand beta 3 of the von Willebrand factor A1 domain inhibits its binding to platelet glycoprotein Ibalpha. Blood 2003; 101: 1375-1383.
  • 26 Reininger AJ, Heijnen HF, Schumann H. et al. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006; 107: 3537-3545.
  • 27 Casonato A, Steffan A, Pontara E. et al. Post- DDAVP thrombocytopenia in type 2B von Willebrand disease is not associated with platelet consumption: failure to demonstrate glycocalicin increase or platelet activation. Thromb Haemost 1999; 81: 224-228.
  • 28 Ruggeri ZM, Orje JN, Habermann R. et al. Activation- independent platelet adhesion and aggregation under elevated shear stress. Blood 2006; 108: 1903-1910.
  • 29 Santoro SA. Adsorption of von Willebrand factor/ factor VIII by the genetically distinct interstitial collagens. Thromb Res 1981; 21: 689-691.
  • 30 Koedam JA, Meijers JC, Sixma JJ, Bouma BN. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. J Clin Invest 1988; 82: 1236-1243.
  • 31 Bendetowicz AV, Wise RJ, Gilbert GE. Collagenbound von Willebrand factor has reduced affinity for factor VIII. J Biol Chem 1999; 274: 12300-12307.
  • 32 Chung DW, Fujikawa K. Processing of von Willebrand factor by ADAMTS-13. Biochemistry 2002; 41: 11065-11070.
  • 33 Dong JF, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
  • 34 Terrell DR, Williams LA, Vesely SK. et al. The incidence of thrombotic thrombocytopenic purpura- hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost 2005; 3: 1432-1436.
  • 35 Conway DS, Pearce LA, Chin BS. et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003; 107: 3141-3145.
  • 36 Lip GY, Blann AD. Von Willebrand factor and its relevance to cardiovascular disorders. Br Heart J 1995; 74: 580-583.
  • 37 Vischer UM. Von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost 2006; 4: 1186-1193.
  • 38 Charles MA, Morange P, Eschwege E. et al. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Diabetes Care 1998; 21: 1967-1972.
  • 39 Blann AD, Jackson P, Bath PM, Watts GF. Von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long-term compliance with a lipid-lowering diet. J Intern Med 1995; 237: 557-561.
  • 40 Blann AD, Waite MA. Von Willebrand factor and soluble E-selectin in hypertension: influence of treatment and value in predicting the progression of atherosclerosis. Coron Artery Dis 1996; 7: 143-147.
  • 41 Goto S, Sakai H, Ikeda Y, Handa S. Acute myocardial infarction plasma augments platelet thrombus growth in high shear rates. Lancet 1997; 349: 543-544.
  • 42 Goto S, Sakai H, Goto M. et al. Enhanced shear-induced platelet aggregation in acute myocardial infarction. Circulation 1999; 99: 608-613.
  • 43 Yamashita A, Sumi T, Goto S. et al. Detection of von Willebrand factor and tissue factor in platelets- fibrin rich coronary thrombi in acute myocardial infarction. Am J Cardiol 2006; 97: 26-28.
  • 44 Hoshiba Y, Hatakeyama K, Tanabe T. et al. Co-localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction. J Thromb Haemost 2006; 4: 114-120.
  • 45 Lee KW, Blann AD, Lip GY. Effects of omega-3 polyunsaturated fatty acids on plasma indices of thrombogenesis and inflammation in patients post-myocardial infarction. Thromb Res 2006; 118: 305-312.
  • 46 Cucuianu MP, Missits I, Olinic N, Roman S. Increased ristocetin-cofactor in acute myocardial in- farction: a component of the acute phase reaction. Thromb Haemost 1980; 43: 41-44.
  • 47 Haines AP, Howarth D, North WR. et al. Haemo - static variables and the outcome of myocardial infarction. Thromb Haemost 1983; 50: 800-803.
  • 48 Vaziri ND, Kennedy SC, Kennedy D, Gonzales E. Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris. Am J Med 1992; 93: 651-657.
  • 49 Yazdani S, Simon AD, Kovar L. et al. Percutaneous interventions alter the hemostatic profile of patients with unstable versus stable angina. J Am Coll Cardiol 1997; 30: 1284-1287.
  • 50 Eto K, Isshiki T, Yamamoto H. et al. AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol 1999; 19: 877-882.
  • 51 Lip GY, Lydakis C, Nuttall SL. et al. A pilot study of streptokinase-induced endothelial injury and platelet activation following acute myocardial infarction. J Intern Med 2000; 248: 316-318.
  • 52 Sakai H, Goto S, Kim JY. et al. Plasma concentration of von Willebrand factor in acute myocardial infarction. Thromb Haemost 2000; 84: 204-209.
  • 53 Tanigawa T, Nishikawa M, Kitai T. et al. Increased platelet aggregability in response to shear stress in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazol after coronary intervention. Am J Cardiol 2000; 85: 1054-1059.
  • 54 Qi X, Peng Y, Gu J. et al. Inflammatory cytokine release in patients with unstable angina after coronary angioplasty. Jpn Heart J 2002; 43: 103-115.
  • 55 Frossard M, Fuchs I, Leitner JM. et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004; 110: 1392-1397.
  • 56 Lee KW, Blann AD, Lip GY. Interrelationships of indices of endothelial damage/dysfunction to tissue factor and interleukin-6 in acute coronary syndromes. Int J Cardiol 2006; 111: 302-308.
  • 57 Lee KW, Lip GY, Tayebjee M. et al. Circulating endothelial cells, von Willebrand factor, interleukin- 6, and prognosis in patients with acute coronary syndromes. Blood 2005; 105: 526-532.
  • 58 Tousoulis D, Bosinakou E, Kotsopoulou M. et al. Effects of early administration of atorvastatin treatment on thrombotic process in normocholesterolemic patients with unstable angina. Int J Cardiol 2006; 106: 333-337.
  • 59 Thompson SG, Kienast J, Pyke SD. et al. Hemo - static factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332: 635-641.
  • 60 Jansson JH, Nilsson TK, Johnson O. Von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66: 351-355.
  • 61 Wiman B, Andersson T, Hallqvist J. et al. 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: 2019-2023.
  • 62 Kaikita K, Soejima K, Matsukawa M. et al. Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction. J Thromb Haemost 2006; 4: 2490-2493.
  • 63 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.
  • 64 Collet JP, Montalescot G, Vicaut E. et al. Acute release of plasminogen activator inhibitor-1 in STsegment elevation myocardial infarction predicts mortality. Circulation 2003; 108: 391-394.
  • 65 Ray KK, Morrow DA, Gibson CM. et al. Predictors of the rise in VWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRETIMI 23 substudy. Eur Heart J 2005; 26: 440-446.
  • 66 Margulis T, David M, Maor N. et al. The von Willebrand factor in myocardial infarction and unstable angina: a kinetic study. Thromb Haemost 1986; 55: 366-368.
  • 67 Montalescot G, Collet JP, Choussat R. et al. A rise of troponin and/or von Willebrand factor over the first 48 h is associated with a poorer 1-year outcome in unstable angina patients. Int J Cardiol 2000; 72: 293-294.
  • 68 Montalescot G, Collet JP, Lison L. et al. Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina. J Am Coll Cardiol 2000; 36: 110-114.
  • 69 Vila V, Martinez-Sales V, Reganon E. et al. Effects of unfractionated and low molecular weight heparins on plasma levels of hemostatic factors in patients with acute coronary syndromes. Haematologica 2001; 86: 729-734.
  • 70 Hodl R, Huber K, Kraxner W. et al. Comparison of effects of dalteparin and enoxaparin on hemostatic parameters and von Willebrand factor in patients with unstable angina pectoris or non--ST- segment elevation acute myocardial infarction. Am J Cardiol 2002; 89: 589-592.
  • 71 Fuchs I, Frossard M, Spiel A. et al. Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS. J Thromb Haemost 2006; 4: 2547-2552.
  • 72 Campo G, Valgimigli M, Gemmati D. et al. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study. J Am Coll Cardiol 2006; 48: 2178-2185.
  • 73 Blann A, Midgley H, Burrows G. et al. Free radicals, antioxidants, and endothelial cell damage after percutaneous transluminal coronary angioplasty. Coron Artery Dis 1993; 4: 905-910.
  • 74 Kefer JM, Galanti LM, Desmet S. et al. Time course of release of inflammatory markers after coronary stenting: comparison between bare metal stent and sirolimus-eluting stent. Coron Artery Dis 2005; 16: 505-509.
  • 75 Federici AB, Berkowitz SD, Zimmerman TS, Mannucci PM. Proteolysis of von Willebrand factor after thrombolytic therapy in patients with acute myocardial infarction. Blood 1992; 79: 38-44.
  • 76 Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: populationbased estimates. Am J Cardiol 1998; 82: 2N-9N.
  • 77 Sato M, Suzuki A, Nagata K, Uchiyama S. Increased von Willebrand factor in acute stroke patients with atrial fibrillation. J Stroke Cerebrovasc Dis 2006; 15: 1-7.
  • 78 Yip HK, Lai SL, Lan MY. et al. Time course of platelet activation and von Willebrand factor in patients with non-valvular atrial fibrillation after ischemic stroke. Circ J 2007; 71: 321-326.
  • 79 Pinto A, Tuttolomondo A, Casuccio A. et al. Immuno- inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation. Clin Sci (Lond). 2008
  • 80 Bath PM, Blann A, Smith N, Butterworth RJ. Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type and functional outcome. Platelets 1998; 9: 155-159.
  • 81 Nomura E, Kohriyama T, Kozuka K. et al. Sequential changes in von Willebrand factor and soluble thrombomodulin in acute ischemic stroke. J Stroke Cerebrovasc Dis 2001; 10: 257-264.
  • 82 Bongers TN, de Maat MP, van Goor ML. et al. High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke 2006; 37: 2672-2677.
  • 83 Beuth W, Kasprzak H, Wozniak B. et al. Von Willebrand factor in patients with subarachnoid hemorrhage. Neurol Neurochir Pol 2001; 35: 130-134.
  • 84 Roldan V, Marin F, Garcia-Herola A, Lip GY. Correlation of plasma von Willebrand factor levels, an index of endothelial damage/dysfunction, with two point-based stroke risk stratification scores in atrial fibrillation. Thromb Res 2005; 116: 321-325.
  • 85 Smith FB, Lee AJ, Hau CM. et al. Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study. Blood Coagul Fibrinolysis 2000; 11: 43-50.
  • 86 Tsakiris DA, Tschopl M, Jager K. et al. Circulating cell adhesion molecules and endothelial markers before and after transluminal angioplasty in peripheral arterial occlusive disease. Atherosclerosis 1999; 142: 193-200.
  • 87 Smith FB, Lowe GD, Fowkes FG. et al. Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease. Atherosclerosis 1993; 102: 155-162.
  • 88 Woodburn KR, Rumley A, Lowe GD. et al. Clinical, biochemical, and rheologic factors affecting the outcome of infrainguinal bypass grafting. J Vasc Surg 1996; 24: 639-646.
  • 89 Cassar K, Bachoo P, Ford I. et al. Markers of coagulation activation, endothelial stimulation and inflammation in patients with peripheral arterial disease. Eur J Vasc Endovasc Surg 2005; 29: 171-176.
  • 90 Blann AD, Naqvi T, Waite M, McCollum CN. Von Willebrand factor and endothelial damage in essential hypertension. J Hum Hypertens 1993; 7: 107-111.
  • 91 Woodburn KR, Rumley A, Murtagh A, Lowe GD. Acute exercise and markers of endothelial injury in peripheral arterial disease. Eur J Vasc Endovasc Surg 1997; 14: 140-142.
  • 92 McCarthy LJ, Danielson CF, Skipworth EM. et al. Myocardial infarction/injury is relatively common at presentation of acute thrombotic thrombocytopenic purpura: the Indiana University experience. Ther Apher 2002; 6: 2-4.
  • 93 Patschan D, Witzke O, Duhrsen U. et al. Acute myocardial infarction in thrombotic microangiopathies-- clinical characteristics, risk factors and outcome. Nephrol Dial Transplant 2006; 21: 1549-1554.
  • 94 Hasper D, Schrage D, Niesporek S. et al. Extensive coronary thrombosis in thrombotic-thrombocytopenic purpura. Int J Cardiol 2006; 106: 407-409.
  • 95 Lapp H, Shin DI, Kroells W. et al. Cardiogenic shock due to thrombotic thrombocytopenic purpura. Z Kardiol 2004; 93: 486-492.
  • 96 Hoylaerts MF, Thys C, Arnout J, Vermylen J. Recurrent arterial thrombosis linked to autoimmune antibodies enhancing von Willebrand factor binding to platelets and inducing Fc gamma RII receptor- mediated platelet activation. Blood 1998; 91: 2810-2817.
  • 97 Girolami A, Tezza F, Scapin M. et al. Arterial and venous thrombosis in patients with von Willebrand’s disease: a critical review of the literature. J Thromb Thrombolysis 2006; 21: 175-178.
  • 98 Bronte-Stewart B, Botha MC, Krut LH. AB0 blood groups in relation to ischaemic heart disease. Br Med J 1962; 1: 1646-1650.
  • 99 Meade TW, Cooper JA, Stirling Y. et al. Factor VIII, AB0 blood group and the incidence of ischaemic heart disease. Br J Haematol 1994; 88: 601-607.
  • 100 Von Beckerath N, Koch W, Mehilli J. et al. AB0 locus 01 allele and risk of myocardial infarction. Blood Coagul Fibrinolysis 2004; 15: 61-67.
  • 101 O’Brien JR, Green PJ, Salmon G. et al. Desmopressin and myocardial infarction. Lancet 1989; 1: 664-665.
  • 102 McLeod BC. Myocardial infarction in a blood donor after administration of desmopressin. Lancet 1990; 336: 1137-1138.
  • 103 Lowe GD. Desmopressin and myocardial infarction. Lancet 1989; 1: 895-896.
  • 104 Bond L, Bevan D. Myocardial infarction in a patient with hemophilia treated with DDAVP. N Engl J Med 1988; 318: 121.
  • 105 Ruggeri ZM. Von Willebrand factor as a target for antithrombotic intervention. Circulation 1992; 86: III26-III29.
  • 106 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.
  • 107 Mohri H, Yoshioka A, Zimmerman TS, Ruggeri ZM. 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.
  • 108 Montalescot G, Philippe F, Ankri A. et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial. Circulation 1998; 98: 294-299.
  • 109 Gold HK, Gimple LW, Yasuda T. et al. Pharmacodynamic study of F(ab’)2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris. J Clin Invest 1990; 86: 651-659.
  • 110 Turner NA, Moake JL, Kamat SG. et al. Comparative real-time effects on platelet adhesion and aggregation under flowing conditions of in vivo aspirin, heparin, and monoclonal antibody fragment against glycoprotein IIb-IIIa. Circulation 1995; 91: 1354-1362.
  • 111 Goto S, Tamura N, Li M. et al. Different effects of various anti-GPIIb-IIIa agents on shear-induced platelet activation and expression of procoagulant activity. J Thromb Haemost 2003; 1: 2022-2030.
  • 112 Dardik R, Ruggeri ZM, Savion N. et al. Platelet aggregation on extracellular matrix: effect of a recombinant GPIb-binding fragment of VWF. Thromb Haemost 1993; 70: 522-526.
  • 113 Fontayne A, Meiring M, Lamprecht S. et al. The humanized anti-glycoprotein Ib monoclonal antibody h6B4-Fab is a potent and safe antithrombotic in a high shear arterial thrombosis model in baboons. Thromb Haemost 2008; 100: 670-677.
  • 114 Staelens S, Hadders MA, Vauterin S. et al. Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain. J Biol Chem 2006; 281: 2225-2231.
  • 115 Wilson C, Keefe AD. Building oligonucleotide therapeutics using non-natural chemistries. Curr Opin Chem Biol 2006; 10: 607-614.
  • 116 Lee JF, Stovall GM, Ellington AD. Aptamer therapeutics advance. Curr Opin Chem Biol 2006; 10: 282-289.
  • 117 Yamamoto H, Vreys I, Stassen JM. et al. Antagonism of vWF inhibits both injury induced arterial and venous thrombosis in the hamster. Thromb Haemost 1998; 79: 202-210.
  • 118 Kageyama S, Yamamoto H, Nagano M. et al. Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor. Br J Pharmacol 1997; 122: 165-171.
  • 119 Kageyama S, Yamamoto H, Yoshimoto R. Antihuman von willebrand factor monoclonal antibody AJvW-2 prevents thrombus deposition and neointima formation after balloon injury in guinea pigs. Arterioscler Thromb Vasc Biol 2000; 20: 2303-2308.
  • 120 Kageyama S, Yamamoto H, Nakazawa H. et al. Pharmacokinetics and pharmacodynamics of AJW200, a humanized monoclonal antibody to von Willebrand factor, in monkeys. Arterioscler Thromb Vasc Biol 2002; 22: 187-192.
  • 121 Kageyama S, Matsushita J, Yamamoto H. Effect of a humanized monoclonal antibody to von Willebrand factor in a canine model of coronary arterial thrombosis. Eur J Pharmacol 2002; 443: 143-149.
  • 122 Gilbert JC, DeFeo-Fraulini T, Hutabarat RM. et al. First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation 2007; 116: 2678-2686.
  • 123 Nylaende M, Kroese A, Stranden E. et al. Prothrombotic activity is associated with the anatomical as well as the functional severity of peripheral arterial occlusive disease. Thromb Haemost 2006; 95: 702-707.