Skip to main content
SpringerLink
Log in

Structure and Function of Platelet Receptors Initiating Blood Clotting

  • Chapter
  • First Online:
A Systems Biology Approach to Blood

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 844))

Abstract

At the clinical level, recent studies reveal the link between coagulation and other pathophysiological processes, including platelet activation, inflammation, cancer, the immune response, and/or infectious diseases. These links are likely to underpin the coagulopathy associated with risk factors for venous thromboembolic (VTE) and deep vein thrombosis (DVT). At the molecular level, the interactions between platelet-specific receptors and coagulation factors could help explain coagulopathy associated with aberrant platelet function, as well as revealing new approaches targeting platelet receptors in diagnosis or treatment of VTE or DVT. Glycoprotein (GP)Ibα, the major ligand-binding subunit of the platelet GPIb-IX-V complex, that binds the adhesive ligand, von Willebrand factor (VWF), is co-associated with the platelet-specific collagen receptor, GPVI. The GPIb-IX-V/GPVI adheso-signaling complex not only initiates platelet activation and aggregation (thrombus formation) in response to vascular injury or disease but GPIbα also regulates coagulation through a specific interaction with thrombin and other coagulation factors. Here, we discuss the structure and function of key platelet receptors involved in thrombus formation and coagulation in health and disease, with a particular focus on platelet GPIbα.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med. 2010;38:S26–34.

    Article  CAS  PubMed  Google Scholar 

  2. del Conde I Shrimpton CN Thiagarajan P López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005;106(5):1604–11.

    Article  CAS  PubMed  Google Scholar 

  3. Müller F, Mutch NJ, Schenk WA, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139(6):1143–56.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Colace TV, Tormoen GW, McCarty OJ, Diamond SL. Microfluidics and coagulation biology. Ann Rev Biomed Eng. 2013;15:283–303.

    Article  CAS  Google Scholar 

  5. Jackson SP, Nesbitt WS, Westein E. Dynamics of platelet thrombus formation. J Thromb Haemost. 2009;7(s1):17–20.

    Article  CAS  PubMed  Google Scholar 

  6. Winckers K, ten Cate H, Hackeng TM. The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis. Blood Rev. 2013;27(3):119–32.

    Article  CAS  PubMed  Google Scholar 

  7. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93(1):327–58.

    Article  CAS  PubMed  Google Scholar 

  8. Chow TW, Hellums JD, Moake JL, Kroll MH. Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. Blood. 1992;80(1):113–20.

    CAS  PubMed  Google Scholar 

  9. Andrews RK, Shen Y, Gardiner EE, Berndt MC. Platelet adhesion receptors and (patho)physiological thrombus formation. Histol Histopathol. 2001;16(3):969–80.

    CAS  PubMed  Google Scholar 

  10. Cosemans JMEM, Schols SEM, Stefanini L, et al. Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow. Blood. 2011;117(2):651–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. van der Meijden PEJ, Schoenwaelder SM, Feijge MAH, et al. Dual P2Y12 receptor signaling in thrombin-stimulated platelets-involvement of phosphoinositide 3-kinase β but not γ isoform in Ca2+ mobilization and procoagulant activity. FEBS J. 2008;275(2):371–85.

    Article  PubMed  Google Scholar 

  12. Choi SH, Smith SA, Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood. 2011;118(26):6963–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Gardiner EE, Karunakaran D, Shen Y, Arthur JF, Andrews RK, Berndt MC. Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. J Thromb Haemost. 2007;5(7):1530–7.

    Article  CAS  PubMed  Google Scholar 

  14. Al-Tamimi M, Grigoriadis G, Tran H, et al. Coagulation-induced shedding of platelet glycoprotein VI mediated by Factor Xa. Blood. 2011;117(14):3912–20.

    Article  CAS  PubMed  Google Scholar 

  15. Rabie T, Strehl A, Ludwig A, Nieswandt B. Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J Biol Chem. 2005;280(15):14462–68.

    Article  CAS  PubMed  Google Scholar 

  16. Andrews RK, Gardiner EE, Shen Y, Whisstock JC, Berndt MC. Glycoprotein Ib-IX-V. Int J Biochem Cell Biol. 2003;35(8):1170–4.

    Article  CAS  PubMed  Google Scholar 

  17. Canobbio I, Balduini C, Torti M. Signalling through the platelet glycoprotein Ib-V-IX complex. Cell Signal. 2004;16(12):1329–44.

    Article  CAS  PubMed  Google Scholar 

  18. López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood. 1998;91(12):4397–418.

    PubMed  Google Scholar 

  19. Cranmer SL, Ashworth KJ, Yao Y, et al. High shear-dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIbα-filamin interaction. Blood. 2011;117(9):2718–27.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Dicker IB, Pedicord DL, Seiffert DA, Jamieson GA, Greco NJ. Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity. Thromb Haemost. 2001;86(4):1065–9.

    CAS  PubMed  Google Scholar 

  21. Luo S-Z, Mo X, Afshar-Kharghan V, Srinivasan S, Lopez JA, Li R. Glycoprotein Ibα forms disulfide bonds with 2 glycoprotein Ibβ subunits in the resting platelet. Blood. 2007;109(2):603–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Andrews RK, Berndt MC, López JA. The glycoprotein Ib-IX-V complex. In Michelson AD, editor. Platelets. San Diego: Academic; 2006:145–63.

    Google Scholar 

  23. Ward CM, Andrews RK, Smith AI, Berndt MC. Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibα. Identification of the sulfated tyrosine/anionic sequence Tyr-276-Glu-282 of glycoprotein Ibα as a binding site for von Willebrand factor and α-thrombin. Biochemistry. 1996;35(15):4929–38.

    Article  CAS  PubMed  Google Scholar 

  24. Cauwenberghs N, Vanhoorelbeke K, Vauterin S, et al. Epitope mapping of inhibitory antibodies against platelet glycoprotein Ibα reveals interaction between the leucine-rich repeat N-terminal and C-terminal flanking domains of glycoprotein Ibα. Blood. 2001;98(3):652–60.

    Article  CAS  PubMed  Google Scholar 

  25. Shen Y, Romo GM, Dong JF, et al. Requirement of leucine-rich repeats of glycoprotein (GP) Ibα for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib-IX-V complex. Blood. 2000;95(3):903–10.

    CAS  PubMed  Google Scholar 

  26. 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(11):1490–2.

    CAS  PubMed  Google Scholar 

  27. Li CQ, Vindigni A, Sadler JE, Wardell MR. Platelet glycoprotein Ibα binds to thrombin anion-binding exosite II inducing allosteric changes in the activity of thrombin. J Biol Chem. 2001;276(9):6161–8.

    Article  CAS  PubMed  Google Scholar 

  28. Huizinga EG, Tsuji S, Romijn RAP, et al. Structures of glycoprotein Ibα and its complex with von Willebrand Factor A1 domain. Science. 2002;297(5584):1176–9.

    Article  CAS  PubMed  Google Scholar 

  29. Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L. Crystal structure of the GPIbα-thrombin complex essential for platelet aggregation. Science.2003;301(5630): 222–6.

    Article  CAS  PubMed  Google Scholar 

  30. Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem. 2000;275(30):22756–42.

    Article  CAS  PubMed  Google Scholar 

  31. Yun TH, Baglia FA, Myles T, et al. Thrombin activation of factor XI on activated platelets requires the interaction of factor XI and platelet glycoprotein Ibα with thrombin anion-binding exosites I and II, respectively. J Biol Chem. 2003;278(48):48112–9.

    Article  CAS  PubMed  Google Scholar 

  32. Joseph K, Nakazawa Y, Bahou WF, Ghebrehiwet B, Kaplan AP. Platelet glycoprotein Ib: a zinc-dependent binding protein for the heavy chain of high-molecular-weight kininogen. Mol Med. 1999;5(8):555–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. 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(6):803–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Simon DI, Chen Z, Xu H, et al. Platelet glycoprotein Ibα is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med. 2000;192(2):193–204.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Arthur JF, Gardiner EE, Matzaris M, et al. Glycoprotein VI is associated with GPIb-IX-V on the membrane of resting and activated platelets. Thromb Haemost. 2005;93(4):716–23.

    CAS  PubMed  Google Scholar 

  36. Cruz MA, Diacovo TG, Emsley J, Liddington R, Handin RI. Mapping the glycoprotein Ib-binding site in the von Willebrand factor A1 domain. J Biol Chem. 2000;275(25):19098–105.

    Article  CAS  PubMed  Google Scholar 

  37. Shen Y, Dong Jf JF, Romo GM, et al. Functional analysis of the C-terminal flanking sequence of platelet glycoprotein Ibα using canine-human chimeras. Blood. 2002;99(1):145–50.

    Article  CAS  PubMed  Google Scholar 

  38. Shen Y, Cranmer SL, Aprico A, et al. Leucine-rich repeats 2-4 (Leu60-Glu128) of platelet glycoprotein Ibα regulate shear-dependent cell adhesion to von Willebrand factor. J Biol Chem. 2006; 281 (36): 26419–26423.

    Article  CAS  PubMed  Google Scholar 

  39. Dumas JJ, Kumar R, McDonagh T, et al. Crystal structure of the wild-type von Willebrand Factor A1-glycoprotein Iba complex reveals conformation differences with a complex bearing von Willebrand Disease mutations. J Biol Chem. 2004;279(22):23327–34.

    Article  CAS  PubMed  Google Scholar 

  40. McEwan PA, Andrews RK, Emsley J. Glycoprotein Ibα inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism. Blood. 2009;114(23):4883–5.

    Article  CAS  PubMed  Google Scholar 

  41. Yago T, Lou J, Wu T, et al. Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF. J Clin Invest. 2008;118(9):3195–207.

    Google Scholar 

  42. Bergmeier W, Piffath CL, Goerge T, et al. The role of platelet adhesion receptor GPIbα far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Proc Natl Acad Sci U S A. 2006;103(45):16900–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Bergmeier W, Chauhan AK, Wagner DD. Glycoprotein Ibα and von Willebrand factor in primary platelet adhesion and thrombus formation: lessons from mutant mice. Thromb Haemost. 2008;99(2):264–70.

    CAS  PubMed  Google Scholar 

  44. Ravanat C, Strassel C, Hechler B, et al. A central role of GPIb-IX in the procoagulant function of platelets that is independent of the 45-kDa GPIbα N-terminal extracellular domain. Blood. 2010;116(7):1157–64.

    Article  CAS  PubMed  Google Scholar 

  45. Boulaftali Y, Hess PR, Getz TM, et al. Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest. 2013;123(2):908–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Owens AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res. 2011;108(10):1284–97.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11(2):123–34.

    Article  CAS  PubMed  Google Scholar 

  48. Jain S, Harris J, Ware J. Platelets: linking hemostasis and cancer. Arterioscler Thromb Vasc Biol. 2010;30(12):2362–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet-cancer loop. Eur J Internal Med. 2013 24(5):393-400.

    Google Scholar 

  50. Semple JW, Italiano JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11(4):264–74.

    Article  CAS  PubMed  Google Scholar 

  51. Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463–9.

    Article  CAS  PubMed  Google Scholar 

  52. Renne T, Pozgajova M, Gruner S, et al. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med. 2005;202(2):271–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Chavakis T, Santoso S, Clemetson KJ, et al. High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib. J Biol Chem. 2003;278(46):45375–81.

    Article  CAS  PubMed  Google Scholar 

  54. Liu J, Gao B-B, Clermont AC, et al. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med. 2011;17(2):206–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Morrissey JH, Choi SH, Smith SA. Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood. 2012;119(25):5972–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Shantsila E, Kamphuisen PW, Lip GYH. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis. J Thromb Haemost. 2010;8(11):2358–68.

    Article  CAS  PubMed  Google Scholar 

  57. Morel O, Toti F, Hugel B, et al. Procoagulant microparticles. Arterioscler Thromb Vasc Biol. 2006;26(12):2594–604.

    Article  CAS  PubMed  Google Scholar 

  58. Ghosh A, Li W, Febbraio M, et al. Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in mice. J Clin Invest. 2008;118(5):1934–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Pluskota E, Woody NM, Szpak D, et al. Expression, activation, and function of integrin αMβ2 (Mac-1) on neutrophil-derived microparticles. Blood. 2008;112(6):2327–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. De Haas CJC Weeterings C Vughs MM De Groot PG Van Strijp JA Lisman T. Staphylococcal superantigen-like 5 activates platelets and supports platelet adhesion under flow conditions, which involves glycoprotein Ibα and αIIbβ3. J Thromb Haemost. 2009;7(11):1867–74.

    Article  CAS  PubMed  Google Scholar 

  61. Hu H, Armstrong PCJ, Khalil E, et al. GPVI and GPIbα mediate Staphylococcal Superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors. PLoS ONE. 2011;6(4):e19190.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.

    Article  CAS  PubMed  Google Scholar 

  63. Brill A, Fuchs TA, Savchenko AS, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2012;10(1):136–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Ward CM, Tetaz TJ, Andrews RK, Berndt MC. Binding of the von Willebrand factor A1 domain to histone. Thromb Res. 1997;86(6):469–77.

    Article  CAS  PubMed  Google Scholar 

  65. Ezumi Y, Shindoh K, Tsuji M, Takayama H. Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc receptor γ chain complex on human platelets. J Exp Med. 1998;188(2):267–76.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Jandrot-Perrus M, Busfield S, Lagrue A-H, et al. Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily. Blood. 2000;96(5):1798–807.

    CAS  PubMed  Google Scholar 

  67. Suzuki-Inoue K, Tulasne D, Shen Y, et al. Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling. J Biol Chem. 2002;277(24):21561–6.

    Article  CAS  PubMed  Google Scholar 

  68. Ruan CG, Du XP, Xi XD, Castaldi PA, Berndt MC. A murine antiglycoprotein Ib complex monoclonal antibody, SZ2, inhibits platelet aggregation induced by both ristocetin and collagen. Blood. 1987;69(2):570–7.

    CAS  PubMed  Google Scholar 

  69. Ohlmann P, Hechler B, Ravanat C, et al. Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression. J Thromb Haemost. 2008;6(6):1003–11.

    Article  CAS  PubMed  Google Scholar 

  70. Schulte V, Reusch HP, Pozgajova M, Varga-Szabo D, Gachet C, Nieswandt B. Two-phase antithrombotic protection after anti-glycoprotein VI treatment in mice. Arterioscler Thromb Vasc Biol. 2006; 26 (7): 1640–1647.

    Article  CAS  PubMed  Google Scholar 

  71. Gilio K, van Kruchten R, Braun A, et al. Roles of platelet STIM1 and Orai1 in glycoprotein VI- and thrombin-dependent procoagulant activity and thrombus formation. J Biol Chem. 2010;285(31):23629–38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Heemskerk JW, Siljander P, Vuist WM, et al. Function of glycoprotein VI and integrin α2β1 in the procoagulant response of single, collagen-adherent platelets. Thromb Haemost. 1999;81(5):782–92.

    CAS  PubMed  Google Scholar 

  73. Siljander P, Farndale RW, Feijge MAH, et al. Platelet adhesion enhances the glycoprotein VI-dependent procoagulant response: Involvement of p38 MAP kinase and calpain. Arterioscler Thromb Vasc Biol. 2001;21(4):618–27.

    Article  CAS  PubMed  Google Scholar 

  74. Seizer P, Borst O, Langer HF, et al. EMMPRIN (CD147) is a novel receptor for platelet GPVI and mediates platelet rolling via GPVI-EMMPRIN interaction. Thromb Haemost. 2009;101(4):682–6.

    CAS  PubMed  Google Scholar 

  75. Schulz C, von Bruhl ML, Barocke V, et al. EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall. J Thromb Haemost. 2011;9(5):1007–19.

    Article  CAS  PubMed  Google Scholar 

  76. Coller BS, Kalomiris E, Steinberg M, Scudder LE. Evidence that glycocalicin circulates in normal plasma. J Clin Invest. 1984;73(3):794–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Gardiner EE, Arthur JF, Kahn ML, Berndt MC, Andrews RK. Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase. Blood. 2004;104(12):3611–7.

    Article  CAS  PubMed  Google Scholar 

  78. Al-Tamimi M, Arthur JF, Gardiner EE, Andrews RK. Focusing on plasma glycoprotein VI. Thromb Haemost. 2012;107(4):648–55.

    Article  CAS  PubMed  Google Scholar 

  79. Al-Tamimi M, Mu FT, Moroi M, Gardiner EE, Berndt MC, Andrews RK. Measuring soluble platelet glycoprotein VI in human plasma by ELISA. Platelets. 2009;20(3):143–9.

    Article  CAS  PubMed  Google Scholar 

  80. Al-Tamimi M, Gardiner EE, Thom JY, et al. Soluble glycoprotein VI is raised in the plasma of patients with acute ischemic stroke. Stroke. 2011;42(2):498–500.

    Article  CAS  PubMed  Google Scholar 

  81. Bigalke B, Potz O, Kremmer E, et al. Sandwich immunoassay for soluble glycoprotein VI in patients with symptomatic coronary artery disease. Clin Chem. 2011;57(6):898–904.

    Article  CAS  PubMed  Google Scholar 

  82. Al-Tamimi M, Tan C, Qiao J, et al. Pathological shear triggers shedding of vascular receptors: a novel mechanism for downregulation of platelet glycoprotein (GP)VI in stenosed coronary vessels. Blood. 2012;119(18):4311–20.

    Article  CAS  PubMed  Google Scholar 

  83. Gardiner EE, Karunakaran D, Arthur JF, et al. Dual ITAM-mediated proteolytic pathways for irreversible inactivation of platelet receptors: De-ITAM-izing FcγRIIa. Blood. 2008;111(1):165–74.

    Article  CAS  PubMed  Google Scholar 

  84. Gardiner EE, Al-Tamimi M, Mu FT, et al. Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura. J Thromb Haemost. 2008;6(7):1175–82.

    Article  CAS  PubMed  Google Scholar 

  85. Reilly MP, Taylor SM, Hartman NK, et al. Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcγRIIA. Blood. 2001;98(8):2442–7.

    Article  CAS  PubMed  Google Scholar 

  86. Warkentin TE, Hayward CP, Boshkov LK, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood. 1994;84(11):3691–9.

    CAS  PubMed  Google Scholar 

  87. Tardy-Poncet B, Piot M, Chapelle C, et al. Thrombin generation and heparin-induced thrombocytopenia. J Thromb Haemostas. 2009;7(9):1474–81.

    Article  CAS  Google Scholar 

  88. Andrews RK, Du X, Berndt MC. The 14-3-3ζ-GPIb-IX-V complex as an antiplatelet target. Drug News Perspect. 2007;20(5):285–92.

    Article  CAS  PubMed  Google Scholar 

  89. Clemetson KJ, Clemetson JM. Platelet GPIb complex as a target for anti-thrombotic drug development. Thromb Haemost. 2008;99(3):473–9.

    CAS  PubMed  Google Scholar 

  90. Jackson SP. Arterial thrombosis-insidious, unpredictable and deadly. Nat Med. 2011;17(11):1423–36.

    Article  CAS  PubMed  Google Scholar 

  91. Wei AH, Schoenwaelder SM, Andrews RK, Jackson SP. New insights into the haemostatic function of platelets. Br J Haematol. 2009;147(4):415–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia

    Elizabeth E. Gardiner

  2. Australian Centre for Blood Diseases, Monash University, Alfred Medical Research & Education Precinct, Level 6, Burnet Building, 89 Commercial Road, Melbourne, VIC 3004, Australia

    Robert K. Andrews

Authors
  1. Elizabeth E. Gardiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert K. Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert K. Andrews .

Editor information

Editors and Affiliations

  1. Departments of Pediatrics and Cell & Molecular Biology, Northwestern University Feinberg School of Medicine and Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA

    Seth Joel Corey

  2. Department of Statistics, Rice University, Houston, Texas, USA

    Marek Kimmel

  3. Northwestern University Comprehensive Cancer Center, Evanston, Illinois, USA

    Joshua N. Leonard

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gardiner, E., Andrews, R. (2014). Structure and Function of Platelet Receptors Initiating Blood Clotting. In: Corey, S., Kimmel, M., Leonard, J. (eds) A Systems Biology Approach to Blood. Advances in Experimental Medicine and Biology, vol 844. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2095-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation