Platelet receptors and signaling in the dynamics of thrombus formation

Haematologica

Volumn 94, Issue 5, 2009, Pages 700-711

  Rivera, José ^a   Lozano, María Luisa ^a   Navarro Núñez, Leyre ^a   Vicente García, Vicente ^a  

^a UNIVERSITY OF MURCIA   (Spain)

Author keywords

Platelet; Receptors; Thrombus formation

Indexed keywords

ADENOSINE DIPHOSPHATE; ALPHA2BBETA3 INTEGRIN; CD31 ANTIGEN; COLLAGEN RECEPTOR; EPHRIN; EPHRIN RECEPTOR; FIBRINOGEN; G PROTEIN COUPLED RECEPTOR; GLYCOPROTEIN IB; GLYCOPROTEIN V; MEMBRANE RECEPTOR; SERUM AMYLOID P; THROMBIN; THROMBOCYTE RECEPTOR; THROMBOXANE A2; UNCLASSIFIED DRUG; VERY LATE ACTIVATION ANTIGEN 2; VERY LATE ACTIVATION ANTIGEN 5; VERY LATE ACTIVATION ANTIGEN 6; VITRONECTIN RECEPTOR; VON WILLEBRAND FACTOR;

AUTOCRINE EFFECT; BINDING AFFINITY; BLOOD CLOT RETRACTION; BLOOD VESSEL INJURY; HEMOSTASIS; HUMAN; HUMAN CELL; INTRACELLULAR TRANSPORT; PARACRINE SIGNALING; PROTEIN PROTEIN INTERACTION; REVIEW; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOGENESIS; THROMBOSIS;

ANIMALS; BLOOD PLATELETS; HUMANS; MODELS, BIOLOGICAL; PLATELET GLYCOPROTEIN GPIB-IX COMPLEX; PLATELET MEMBRANE GLYCOPROTEINS; PROTEIN BINDING; SIGNAL TRANSDUCTION; THROMBOSIS;

EID: 66049107647     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2008.003178     Document Type: Review

References (110)

1. Clemetson KJ, Clemetson JM. Platelet receptors. In: Michelson AD, editor. Platelets 2nd ed. San Diego, CA: Elsevier/Academic Press; 2007, p.117-143
2. George JN. Platelets. Lancet 2000; 355:1531-1539
3. Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007;100:1673-1685 (Pubitemid 46987859)
4. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007;357:2482-2494
5. Prandoni P. Links between arterial and venous disease. J Intern Med 2007;262:341-350 (Pubitemid 47246969)
6. Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008;359:938-949
7. Cosemans JMEM, Munnix ICA, Wetzker R, Heller R, Jackson SP, Heemskerk JWM. Continuous signalling via PI3K isoforms β and γ is required for platelet ADP receptor function in dynamic thrombus stabilization. J Thromb Haemost 2006; 108:3045-3052
8. 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 (Pubitemid 28427584)
9. Jackson SP, Nesbitt WS, Kulkarni S. Signaling event underlying thrombus formation. J Thromb Haemost 2003;1:1602-1612
10. Siedlecki CA, Lestini BJ, Kottke- Marchant KK, Eppell SJ, Wilson DL, Marchant RE. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 1996;88:2939-2950 (Pubitemid 26357374)
11. 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 USA 2007;104:7899-7903
12. Rivera J, Lozano ML, Corral J, González-Conejero R, Martínez C, Vicente V. Platelet GP Ib/IX/V complex: physiological role. J Physiol Biochem 2000;56:355-365 (Pubitemid 33601115)
13. Luo SZ, Mo X, Afshar-Kharghan V, Srinivasan S, Lopez JA, Li R. Glycoprotein Ibalpha forms disulfide bonds with 2 glycoproteins Ibbeta subunits in the resting platelets. Blood 2007;109:603-609 (Pubitemid 46105958)
14. Bergmeier W, Piffath CL, Goerge T, Cifuni SM, Ruggeri ZM, Ware J, et al. The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci USA 2006;103:16900-16905
15. Dubois C, Panicot-Dubois L, Gainor JF, Furie BC, Furie B. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Invest 2007;117:953-960 (Pubitemid 46556751)
16. Wu D, Vanhoorelbeke K, Cauwenberghs N, Meiring M, Depraetere H, Kotze HF, 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
17. Fontayne A, Vanhoorelbeke K, Pareyn I, Van Rompaey I, Meiring M, Lamprecht S, et al. Rational humanization of the powerful antithrombotic anti-GPIbalpha antibody: 6B4. Thromb Haemost 2006; 96:671-684
18. Ozaki Y, Asazuma N, Suzuki-Inoue, Berndt MC. Platelet GPIb/IX/Vdependent signaling. J Thromb Haemost 2005;3:1745-1751
19. Du X. Signaling and regulation of the glycoprotein Ib/IX/V complex. Curr Opin Hematol 2007;14:262-269 (Pubitemid 46597613)
20. López JA, del Conde I, Shrimpton CN. Receptors, rafts, and microvesicles in thrombosis and inflammation. J Thromb Haemost 2005;3: 1737-1744 (Pubitemid 41716560)
21. Gibbins JM. Platelet adhesion signalling and the regulation of thrombus formation. J Cell Sci 2004;117: 3415-3425 (Pubitemid 39206382)
22. Savage B, Ginsberg MH, Ruggeri ZM. Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow. Blood 1999;94:2704-2715 (Pubitemid 29477299)
23. Nieswandt B, Watson SP. Plateletcollagen interaction: is GPVI the central receptor? Blood 2003;102: 449-461
24. Watson SP, Auger JM, McCarty OJ, Pearce AC. GPVI and intregrin αIIbβ3 signaling in platelets. J Thromb Haemost 2005;3:1752-1762 (Pubitemid 41716562)
25. Kato K, Kanaji T, Russell S, Kunicki TJ, Furihata K, Kanaji S, et al. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 2003;102: 1701-1707
26. Poole A, Gibbins JM, Turner M, van Vugt MJ, van de Winkel JG, Saito T, et al. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 1997; 16:2333-2341
27. Li H, Lockyer S, Concepcion A, Gong X, Takizawa H, Guertin M, et al. The Fab fragment of a novel anti- GPVI monoclonal antibody, OM4, reduces in vivo thrombosis without bleeding risk in rats. Arterioscler Thromb Vasc Biol 2007;27:1199-1205
28. Corral J, González-Conejero R, Rivera J, Ortuño F, Aparicio P, Vicente V. Role of the 807 C/T polymorphism of the alpha2 gene in platelet GP Ia collagen receptor expression and function-effect in thromboembolic diseases. Thromb Haemost 1999;81:951-956 (Pubitemid 29312714)
29. Kritzik M, Savage B, Nugent DJ, Santoso S, Ruggeri ZM, Kunicki TJ. Nucleotide polymorphisms in the α2 gene define multiple alleles that are associated with differences in platelet α2 β1 density. Blood 1998; 92:2382-2388 (Pubitemid 28452981)
30. Nieuwenhuis HK, Akkerman JW, Houdijk WP, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985;318:470-472 (Pubitemid 16195848)
31. Holtkötter O, Nieswandt B, Smyth N, Müller W, Hafner M, Schulte V, et al. Integrin α 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen. J Biol Chem 2002;277:10789-10794
32. Grüner S, Prostredna M, Schulte V, Krieg T, Eckes B, Brakebusch C, et al. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo. Blood 2003;102:4021-4027
33. He L, Pappan LK, Grenache DG, Li Z, Tollefsen DM, Santoro SA, el al. The contributions of the alpha2 beta1 integrin to vascular thrombosis in vivo. Blood 2003;102:3652-3657
34. Kuijpers MJ, Pozgajova M, Cosemans JM, Munnix IC, Eckes B, Nieswandt B, et al. Role of murine integrin alpha2beta1 in thrombus stabilization and embolization: contribution of thromboxane A2. Thromb Haemost 2007;98:1072-1080
35. Van de Walle GR, Schoolmeester A, Iserbyt BF, Cosemans JM, Heemskerk JW, Hoylaerts MF, et al. Activation of αIIbβ3 is a sufficient but also an imperative prerequisite for activation of α2β1 on platelets. Blood 2007;109:595-602.
36. Cosemans JM, Iserbyt BF, Deckmyn H, Heemskerk JW. Multiple ways to switch platelet integrins on and off. J Thromb Haemost 2008;6:1253-1261
37. Sarratt KL, Chen H, Zutter MM, Santoro SA, Hammer DA, Kahn ML. GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood 2005; 106:1268-1277 (Pubitemid 41129590)
38. Arthur JF, Dunkley S, Andrews RK. Platelet glycoprotein VI-related clinical defects. Br J Haematol 2007;139: 363-372 (Pubitemid 47515353)
39. Barret NE, Jones L, Kaiser WJ, Moraes LA, Rana R, Sage T, et al. Future innovations in anti-platelet therapies. Br J Pharmacol 2008; 154: 918-939
40. Petrich BG, Marchese P, Ruggeri ZM, Spiess S, Weichert RA, Ye F, et al. Talin is required for integrinmediated platelet function in hemostasis and thrombosis. J Exp Med 2007;204:3103-3111
41. Han J, Lim CJ, Watanabe N, Soriani A, Ratnikov B, Calderwood DA, et al. 2006. Reconstructing and deconstructing agonist-induced activation of integrin αIIbβ3. Curr Biol 2006; 16:1796-1806
42. Moser M, Nieswandt B, Ussar S, Pozgajova M, Fässler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med 2008; 14:325-330
43. Pasvolsky R, Feigelson SW, Kilic SS, Simon AJ, Tal-Lapidot G, Grabovsky V, et al. LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med 2007;204:1571-1582
44. Kuijpers TW, van de Vijver E, Weterman MA, de Boer M, Tool AT, van den Berg TK, et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood 2008 Dec 8 [Epub ahead of print as doi: 10.1182/blood-2008-10-182154].
45. Offermanns S. Activation of platelet function through G protein-coupled receptors. Circ Res 2006;99:1293-1304
46. Woulfe D, Yang J, Prevost N, O'Brien P, Fortna R, Tognolini M, et al. Signaling receptors on platelets and megakaryocytes. Methods Mol Biol 2004;273:3-31.
47. Gachet C. P2 receptors, platelet function and pharmacological implications. Thromb Haemost 2008;99: 466-472
48. Jirouskova M, Shet AS, Johnson GJ. A guide to murine platelet structure, function, assays, and genetic alterations. J Thromb Haemost 2007;5: 661-669 (Pubitemid 46563562)
49. Salles II, Feys HB, Iserbyt BF, De Meyer SF, Vanhoorelbeke K, Deckmy H. Inherited traits affecting platelet function. Blood Rev 2008; 22:155-172
50. Hechler B, Zhang Y, Eckly A, Cazenave JP, Gachet C, Ravid K. Lineage-specific overexpression of the P2Y1 receptor induces platelet hyper-reactivity in transgenic mice. J Thromb Haemost 2003;1:155-163
51. Nakahata N. Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 2008;118: 18-35.
52. Niccoli G, Giubilato S, Russo E, Spaziani C, Leo A, Porto I, et al. Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention. Eur Heart J 2008;29:1843-1850.
53. Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 2008; 51:1829-1843.
54. Barstad RM, Orvim U, Hamers MJ, Tjønnfjord GE, Brosstad FR, Sakariassen KS. Reduced effect of aspirin on thrombus formation at high shear and disturbed laminar blood flow. Thromb Haemost 1996; 75:827-832 (Pubitemid 26181858)
55. Maalej N, Folts JD. Increased shear stress overcomes the antithrombotic platelet inhibitory effect of aspirin in stenosed dog coronary arteries. Circulation 1996;9:1201-1205 (Pubitemid 26087023)
56. Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Cir Res 2007; 100:1261-1275 (Pubitemid 46742917)
57. Huang JS, Ramamurthy SK, Lin X, Le Breton GC. Cell signaling through thromboxane A2 receptors. Cell Signal 2004;16:521-533 (Pubitemid 38125140)
58. Nieswandt B, Aktas B, Mores A, Sachs UJH. Platelet in atherothrombosis: lesson from mouse models. J Thromb Haemost 2005;3:1725-1736 (Pubitemid 41716559)
59. Crawley JTB, Zarnardelli S, Chion CKN, Lane DA. The central role of thrombin in hemostasis. J Thromb Haemost 2007;5 (Suppl 1):95-101. (Pubitemid 46958822)
60. Vandendries ER, Hamilton JR, Coughlin SR, Furie B, Furie BC. Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci USA 2007; 104:288-292 (Pubitemid 46068024)
61. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005;3:1800-1814 (Pubitemid 41716567)
62. Mazzucato M, Marco LD, Masotti A, Pradella P, Bahou WF, Ruggeri ZM. Characterization of the initial alpha-thrombin interaction with glycoprotein Ib alpha in relation to platelet activation.J Biol Chem 1998; 273:1880-1887.
63. Celikel R, McClintock RA, Roberts JR, Mendolicchio GL, Ware J, Varughese KI, et al. Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Iba. Science 2003;301:218-221
64. Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L. Crystal structure of the GpIbα-thrombin complex essential for platelet aggregation. Science 2003;301:222-226 (Pubitemid 36868962)
65. Adam F, Guillin MC, Jandrot-Perrus M. Glycoprotein Ib-mediated platelet activation. A signaling pathway triggered by thrombin. Eur J Biochem 2003;270:2959-2970
66. López JA, Andrews RK, Afshar- Kharghan V, Berndt MC. Bernard- Soulier Syndrome. Blood 1998;91: 4397-4418
67. nd, Ruggeri ZM. Function of glycoprotein Ib α in platelet activation induced by alphathrombin. J Biol Chem 1991;266: 23776-23783
68. Lozano ML, Rivera J, González- Conejero R, Moraleda JM, Vicente V. Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin. Transfusion 1997;37:368-375 (Pubitemid 27193549)
69. De Candia E, Hall SW, Rutella S, Landolfi R, Andrews RK, De Cristofaro R. Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets. J Biol Chem 2001;276: 4692-4698 (Pubitemid 37371351)
70. Ramakrishnan V, Reeves PS, DeGuzman F, Deshpande U, Ministri-Madrid K, DuBridge RB, et al. Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc Natl Acad Sci USA 1999;96:13336-13341
71. Ni H, Ramakrishnan V, Ruggeri ZM, Papalia JM, Phillips DR, Wagner DD. Increased thrombogenesis and embolus formation in mice lacking glycoprotein V. Blood 2001;98:368-373
72. Ramakrishnan V, DeGuzman F, Bao M, Hall SW, Leung LL, Phillips DR. A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V. Proc Natl Acad Sci USA 2001;98:1823-1828. (Pubitemid 32165582)
73. Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry 2000;39:5458-5467 (Pubitemid 30257087)
74. Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 2001;293: 1666-1670 (Pubitemid 32807847)
75. Sambrano GR, Weiss EJ, Zheng YW, Huang W, Coughlin SR. Role of thrombin signaling in platelets in haemostasis and thrombosis. Nature 2001;413:74-78 (Pubitemid 32843490)
76. Weiss EJ, Hamilton JR, Lease KE, Coughlin SR. Protection against thrombosis in mice lacking PAR3. Blood 2002;100:3240-3244 (Pubitemid 35217073)
77. Derian CK, Damiano BP, Addo MF, Darrow AL, D'Andrea MR, Nedelman M, et al. Blockade of the thrombin receptor protease-activated receptor-1 with a small-molecule antagonist prevents thrombus formation and vascular occlusion in nonhuman primates. J Pharmacol Exp Ther 2003;304:855-861
78. Rao AK, Willis J, Kowalska MA, Wachtfogel YT, Colman RW. Differential requirements for platelet aggregation and inhibition of adenylate cyclase by epinephrine. Studies of a familial platelet α 2- adrenergic receptor defect. Blood 1988;71:494-501.
79. Yang J, Wu J, Kowalska MA, Dalvi A, Prevost N, O'Brien PJ, et al. Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs. Proc Natl Acad Sci USA 2000;97:9984-9989
80. Pozgajová M, Sachs UJ, Hein L, Nieswandt B. Reduced thrombus stability in mice lacking the a2Aadrenergic receptor. Blood 2006; 108:510-514
81. Wang JS, Cheng LJ. Effect of strenuous, acute exercise on alpha2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 1999;19:1559-1565 (Pubitemid 29263029)
82. Kaywin P, McDonough M, Insel PA, Shattil SJ. Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet α- adrenergic receptors. N Engl J Med 1978;299:505-509
83. Yabe M, Matsubara Y, Takahashi S, Ishihara H, Shibano T, Miyaki K, et al. Identification of ADRA2A polymorphisms related to shear-mediated platelet function. Biochem Biophys Res Commun 2006;347: 1001-1005
84. Yee DL, Bergeron AL, Sun CW, Dong JF, Bray PF. Platelet hyperreactivity generalizes to multiple forms of stimulation. J Thromb Haemost 2006;4:2043-2050 (Pubitemid 44226787)
85. Bray PF, Mathias RA, Faraday N, Yanek LR, Fallin MD, Herrera- Galeano JE, et al. Heritability of platelet function in families with premature coronary artery disease. J Thromb Haemost 2007;5:1617-1623
86. Coller BS, Shattil SJ. The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008;112:3011-3025
87. nd edition, San Diego, CA, USA. Elsevier/Academic Press; 2007. p.347-357
88. Brass LF, Zhu L, Stalker TJ. Novel therapeutic targets at the platelet vascular interface. Arterioscler Thromb Vasc Biol 2008;28:s43-50.
89. Hermann A, Rauch BH, Braun M, Schrör K, Weber AA. Platelet CD40 ligand (CD40L)-subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets 2001;12:74-82. (Pubitemid 32281113)
90. André P, Prasad KS, Denis CV, He M, Papalia JM, Hynes RO, et al. CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism. Nat Med 2002;8:247-252
91. Prévost N, Woulfe DS, Jiang H, Stalker TJ, Marchese P, Ruggeri ZM, et al. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside- in signaling in platelets. Proc Natl Acad Sci USA 2005;102:9820-9825
92. Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, et al. Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci USA 2007;104:1621-1626
93. Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med 2001;7:215-221
94. Saller F, Burnier L, Schapira M, Angelillo-Scherrer A. Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization. Blood Cells Mol Dis 2006;36:373-378 (Pubitemid 43776182)
95. Balogh I, Hafizi S, Stenhoff J, Hansson K, Dahlbäck B. Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol 2005;25:1280-1286 (Pubitemid 40776622)
96. Herrera-Galeano JE, Becker DM, Wilson AF, Yanek LR, Bray P, Vaidya D, et al. A novel variant in the platelet endothelial aggregation receptor-1 gene is associated with increased platelet aggregability. Arterioscler Thromb Vasc Biol 2008;28:1484-1490
97. Nanda N, Phillips DR. Novel targets for antithrombotic drug discovery. Blood Cells Mol Dis 2006;36:228-231
98. Chou J, Mackman N, Merrill- Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104:3190-3197 (Pubitemid 39507134)
99. Falati S, Liu Q, Gross P, Merrill- Skoloff G, Chou J, Vandendries E, et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle Pselectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197:1585-1598
100. Day SM, Reeve JL, Pedersen B, Farris DM, Myers DD, Im M, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 2005;105:192-198
101. López-Vilchez I, Escolar G, Diaz- Ricart M, Fuste B, Galan AM, White JG. Tissue factor-enriched vesicles are taken up by platelets and induce platelet aggregation in the presence of factor VIIa. Thromb Haemost 2007;97:202-211 (Pubitemid 46592140)
102. Panes O, Matus V, Sáez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood 2007;109:5242-5250 (Pubitemid 46890544)
103. Geiger J, Inhibitors of platelet signal transduction as anti-aggregatory drugs. Expert Opin Invest Drugs 2001;10:865-890 (Pubitemid 32427654)
104. Radomski MW, Palmer RM, Moncada S. Endogenous nitricoxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987;2:1057-1058 (Pubitemid 17154788)
105. Wee JL, Jackson DE. The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signalling properties of integrin αIIbβ3 in platelets. Blood 2005;106:3816-3823
106. Rathore V, Stapleton MA, Hillery CA, Montgomery RR, Nichols TC, Merricks EP, et al. PECAM-1 negatively regulates GPIb/V/IX signalling in murine platelets. Blood 2003;102:3658-3664
107. Thai le M, Ashman LK, Harbour SN, Hogarth PM, Jackson DE. Physical proximity and functional interplay of PECAM-1 with the Fc receptor FcgRIIa on the platelet plasma membrane. Blood 2003;102: 3637-3645
108. Cicmil M, Thomas JM, Leduc M, Bon C, Gibbins JM. Platelet endothelial cell adhesion molecule- 1 signaling inhibits the activation of human platelets. Blood 2002;99; 137-144 (Pubitemid 34532975)
109. Andrews RK, Karunakaran D, Gardiner EE, Berndt MC. Platelet receptor proteolysis. A mechanism for downregulating platelet reactivity. Arterioscler Thromb Vasc Biol 2007;27:1511-1520
110. Shida Y, Nishio K, Sugimoto M, Mizuno T, Hamada M, Kato S, et al. Functional imaging of sheardependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions. Blood 2008;111:1295-1298.