Download PDF
Hamostaseologie 2008; 28(05): 289-298
DOI: 10.1055/s-0037-1617177
Hämostaseologie
Schattauer GmbH

Blutplättchen

Biochemie und PhysiologiePlateletsBiochemistry and physiology
B. E. Kehrel
1   Experimentelle und Klinische Hämostaseologie, Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster
› Author Affiliations
Further Information

Publication History

Publication Date:
29 December 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Der Übersichtsartikel beschäftigt sich mit den verschiedenen Rollen der Blutplättchen in physiologischen und pathologischen Prozessen der Hämostase und der Entstehung thromboembolischer Erkrankungen. Neben Kernprozessen der primären Hämostase, Plättchenadhäsion, Plättchen - sekretion, Plättchenaggregation, Gerinnselretraktion wird die moderne Sicht der Bildung von Thrombin auf der Thrombozytenoberfläche geschildert. Ein Schwerpunkt liegt in der Darstellung der verschiedenen Signaltransduktionswege in den Plättchen.

Summary

This article reviews the roles of blood platelets in haemostasis as well as in the pathogenesis of thromboembolic diseases. Besides the basic processes in primary haemostasis, platelet adhesion, platelet secretion, platelet aggregation, clot retraction, the new model of thrombin formation on the platelet surface is presented. The different signal transduction pathways in platelets are a main focus of this review.

Schlüsselwörter

Plättchenadhäsion - Plättchenaggregation - prokoagulanter Zustand - Plättchen-Leukozyten-Interaktion - Plättchen- Gefäßwand-Interaktion

Keywords

Platelet adhesion - platelet aggregation - platelet procoagulant activity - platelet interaction with cells
 

  • Literatur

  • 1 Ahamed J, Versteeg HH, Kerver M. et al. Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc Natl Acad Sci USA 2006; 103: 13932-13937.
    CrossrefPubMedGoogle Scholar
  • 2 Aszodi A, Pfeifer A, Ahmad M. et al. The vasodilator- stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist- induced platelet aggregation, but is dispensable for smooth muscle function. EMBO J 1999; 18: 37-48.
    CrossrefPubMedGoogle Scholar
  • 3 Baglia FA, Shrimpton CN, Emsley J. et al. Factor XI interacts with the leucine-rich repeats of glycoprotein Ibalpha on the activated platelet. J Biol Chem 2004; 279: 49323-49329.
    CrossrefPubMedGoogle Scholar
  • 4 Bergmeier W, Piffath CL, Goerge T. 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.
    CrossrefPubMedGoogle Scholar
  • 5 Bevilacqua M, Butcher E, Furie B. et al. Selectins: a family of adhesion receptors. Cell 67 1991: 233.
    PubMedGoogle Scholar
  • 6 Bouchard BA, Catcher CS, Thrash BR. et al. Effector cell protease receptor-1, a platelet activation- dependent membrane protein, regulates prothrombinase- catalyzed thrombin generation. J Biol Chem 1999; 272: 9244-9251.
    PubMedGoogle Scholar
  • 7 Bouchard BA, Tracy PB. Platelets, leukocytes, and coagulation. Curr Opin Hematol 2001; 8: 263-269.
    CrossrefPubMedGoogle Scholar
  • 8 Brass LF, Hoxie JA, Manning DR. Signaling through G proteins and G protein-coupled receptors during platelet activation. Thromb Haemost 1993; 70: 217-223.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Brass LF, Pizarro S, Ahuja M. et al. Changes in the structure and function of the human thrombin receptor during receptor activation, internalization, and recycling. J Biol Chem 1994; 269: 2943-2952.
    PubMedGoogle Scholar
  • 10 Brass LF. More pieces of the platelet activation puzzle slide into place. J Clin Invest 1999; 104: 1663-1665.
    CrossrefPubMedGoogle Scholar
  • 11 Clemetson JM, Polgar J, Magnenat E. et al. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcalphaR and the natural killer receptors. J Biol Chem 1999; 274: 29019-29024.
    CrossrefPubMedGoogle Scholar
  • 12 Clemetson KJ. Platelet activation: signal transduction via membrane receptors. Thromb Haemost 1995; 74: 111-116.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Clemetson KJ, Clemetson JM. Platelet GPIb-V-IX complex. Structure, function, physiology, and pathology. Semin Thromb Hemost 1995; 21: 130-136.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Clemetson KJ, Clemetson JM. Platelet collagen receptors. Thromb Haemost 2001; 86: 189-197.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990; 322: 33-42.
    CrossrefPubMedGoogle Scholar
  • 16 Coller BS. Antiplatelet agents in the prevention and therapy of thrombosis. Ann Rev Med 1992; 43: 171-180.
    CrossrefPubMedGoogle Scholar
  • 17 Coller BS. GPIIb/IIIa antagonists: pathophysiologic and therapeutic insights from studies of c7E3 Fab. Thromb Haemost 1997; 78: 730-735.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Dale GL, Friese P, Batar P. et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature 2002; 415: 175-179.
    CrossrefPubMedGoogle Scholar
  • 19 Dörmann D, Kardoeus J, Zimmermann RE. et al. Flowcytometric analysis of agonist-induced annexin V, factor Va and factor Xa binding to human platelets. Platelets 1998; 9: 171-177.
    CrossrefPubMedGoogle Scholar
  • 20 Dormann D, Clemetson KJ, Kehrel BE. The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. Blood 2000; 96: 2469-2478.
    CrossrefPubMedGoogle Scholar
  • 21 Fox JE. The platelet cytoskeleton. Thromb Haemost 1993; 70: 884-893.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Frenette PS, Denis CV, Weiss L. et al. P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 2000; 191: 1413-1422.
    CrossrefPubMedGoogle Scholar
  • 23 Fumeron F, Betoulle D, Nicaud V. et al. Serotonin transporter gene polymorphism and myocardial infarction: Etude Cas-Temoins de l’In-farctus du Myocarde (ECTIM). Circulation 2002; 105: 2943-2945.
    CrossrefPubMedGoogle Scholar
  • 24 Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost 2001; 86: 214-221.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Gachet C. ADP receptors of platelets and their inhibition. Thromb Haemost 2001; 86: 222-232.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Gao J, Zoller KE, Ginsberg MH. et al. Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3. EMBO J 1997; 16: 6414-6425.
    CrossrefPubMedGoogle Scholar
  • 27 George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. N Engl J Med 1991; 324: 27-39.
    CrossrefPubMedGoogle Scholar
  • 28 Gewirtz AM, Poncz M. Megakaryocytopoiesis and platelet function. In: Hoffmann R, Benz Jr EJ, Shattil SJ. et al (Hrsg). Hematology, Basic Principles and Practice. New York: Churchill-Livingstone; 1991: 1148-1157.
    Google Scholar
  • 29 Gupta GP, Massagué J. Platelets and metastasis revisited: a novel fatty link. J Clin Invest 2004; 114: 1691-1693.
    CrossrefPubMedGoogle Scholar
  • 30 Hoffman M, Monroe DM, Roberts HR. Plateletdependent action of high-dose factor VIIa. Blood 2002; 100: 364-365.
    CrossrefPubMedGoogle Scholar
  • 31 Holme PA, Orvim U, Hamers MJ. et al. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol 1997; 17: 646-653.
    CrossrefPubMedGoogle Scholar
  • 32 Jurk K, Kehrel BE. The role of platelets in haemostasis, thrombosis, immune defense and inflammation. Dtsch Med Wochenschr 2008; 133: 1130-1135.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Jurk K, Kehrel B. Thrombozytensekretion. In: Hämostaseologie. Madlener K, Pötzsch B, Gawaz M. et al (Hrsg). Heidelberg: Springer; 2008
    Google Scholar
  • 34 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.
    CrossrefPubMedGoogle Scholar
  • 35 Kaushansky K, Drachman JG. The molecular and cellular biology of thrombopoietin: the primary regulator of platelet production. Oncogene 2002; 21: 3359-3367.
    CrossrefPubMedGoogle Scholar
  • 36 Kehrel B, Balleisen L, Kokott R. et al. Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988; 71: 1074-1078.
    PubMedGoogle Scholar
  • 37 Kehrel B. Platelet-collagen interactions. Semin Thromb Hemost 1995; 21: 123-129.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Kehrel B, Flicker E, Wigbels B. et al. Thrombospondin measured in whole blood – an indicator of platelet activation. Blood Coagul Fibrinol 1996; 7: 202-205.
    CrossrefPubMedGoogle Scholar
  • 39 Kehrel BE, Wierwille S, Clemetson KJ. et al. Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not. Blood 1998; 91: 491-499.
    PubMedGoogle Scholar
  • 40 Lahav J, Jurk K, Hess O. et al. Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange. Blood 2002; 100: 2472-2478.
    CrossrefPubMedGoogle Scholar
  • 41 Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008; 99: 480-486.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Lindemann S, Tolley ND, Dixon DA. et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154: 485-490.
    CrossrefPubMedGoogle Scholar
  • 43 Lüscher EF, Weber S. The formation of the haemostatic plug – a special case of platelet aggregation. An experiment and a survey of the literature. Thromb Haemost 1993; 70: 234-237.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Marcus AJ, Broekman MJ, Drosopoulos JH. et al. The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39. J Clin Invest 1997; 99: 1351-1360.
    CrossrefPubMedGoogle Scholar
  • 45 May AE, Seizer P, Gawaz M. Platelets: inflammatory firebugs of vascular walls. Arterioscler Thromb Vasc Biol 2008; 28: s5-s10.
    CrossrefPubMedGoogle Scholar
  • 46 Monroe DM, Hoffman M, Oliver JA. et al. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol 1997; 99: 542-547.
    CrossrefPubMedGoogle Scholar
  • 47 Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 2002; 22: 1381-1389.
    CrossrefPubMedGoogle Scholar
  • 48 Morgenstern E, Kehrel BE, Matzdorff A. et al. How do platelets aggregate? 45th Meeting of the GTH, 17.2. 2001 Düsseldorf. Ann Hematol 2001; 80: A48.
    PubMedGoogle Scholar
  • 49 Morgenstern E. Morphologie der Thrombozyten. In: Müller-Berghaus G, Pötzsch B. (Hrsg). Hämostaseologie. Berlin, Heidelberg: Springer; 1999: 1-14.
    Google Scholar
  • 50 Nesheim ME, Furmaniak-Kazmierczak E, Henin C. et al. On the existence of platelet receptors for factor V(a) and factor VIII(a). Thromb Haemost 1993; 70: 80-86.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Newman PJ. Switched at birth: a new family for PECAM-1. J Clin Invest 1999; 103: 5-9.
    CrossrefPubMedGoogle Scholar
  • 52 Newton-Nash DK, Newman PJ. A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction. J Immunol 1999; 163: 682-688.
    PubMedGoogle Scholar
  • 53 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC. et al. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997; 96: 3534-3541.
    CrossrefPubMedGoogle Scholar
  • 54 Oliver JA, Monroe DM, Roberts HR. et al. Thrombin activates factor XI on activated platelets in the absence of factor XII. Arterioscler Thromb Vasc Biol 1999; 19: 170-177.
    CrossrefPubMedGoogle Scholar
  • 55 Phillips DR, Law D, Scarborough RM. Glycoprotein IIb-IIIa in platelet aggregation: an emerging target for the prevention of acute coronary thrombotic occlusions. Arch Pathol Lab Med 1998; 122: 811-812.
    PubMedGoogle Scholar
  • 56 Polgar J, Clemetson JM, Kehrel BE. et al. Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J Biol Chem 1997; 272: 13576-13583.
    CrossrefPubMedGoogle Scholar
  • 57 Rao AK. Congenital disorders of platelet function. Hematol Oncol Clin North Am 1990; 4: 65-86.
    CrossrefPubMedGoogle Scholar
  • 58 Rao AK. Congenital disorders of platelet function: disorders of signal transduction and secretion. Am J Med Sci 1998; 316: 69-76.
    PubMedGoogle Scholar
  • 59 Reinhardt C, von Brühl ML, Manukyan D. et al. Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. J Clin Invest 2008; 118: 1110-1122.
    PubMedGoogle Scholar
  • 60 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.
    CrossrefPubMedGoogle Scholar
  • 61 Rinder CS, Student LA, Bonan JL. et al. Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release. Blood 1993; 82: 505-512.
    PubMedGoogle Scholar
  • 62 Romo GM, Dong JF, Schade AJ. et al. The glycoprotein Ib-IX-V complex is a platelet counterre-ceptor for P- selectin. J Exp Med 1999; 190: 803-814.
    CrossrefPubMedGoogle Scholar
  • 63 Ruggeri ZM. Mechanisms of shear-induced platelet adhesion and aggregation. Thromb Haemost 1993; 70: 119-123.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 64 Savage B, Shattil SJ, Ruggeri ZM. Modulation of platelet function through adhesion receptors. A dual role for glycoprotein IIb-IIIa (integrin alpha IIb beta 3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. J Biol Chem 1992; 267: 11300-11306.
    PubMedGoogle Scholar
  • 65 Scandura JM, Walsh PN. Factor X bound to the surface of activated human platelets is preferentially activated by platelet-bound factor IXa. Biochemistry 1996; 35: 8903-8913.
    CrossrefPubMedGoogle Scholar
  • 66 Schulz C, Penz S, Hoffmann C. et al. Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol 2008; 103: 356-367.
    CrossrefPubMedGoogle Scholar
  • 67 Schwarz UR, Walter U, Eigenthaler M. Taming platelets with cyclic nucleotides. Biochem Pharmacol 2001; 62: 1153-1161.
    CrossrefPubMedGoogle Scholar
  • 68 Shattil SJ, Ginsberg MH, Brugge JS. Adhesive signaling in platelets. Curr Opin Cell Biol 1994; 6: 695-704.
    CrossrefPubMedGoogle Scholar
  • 69 Sims PJ, Wiedmer T, Esmon CT. et al. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 1989; 264: 17049-17057.
    PubMedGoogle Scholar
  • 70 Von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 2007; 100: 27-40.
    CrossrefPubMedGoogle Scholar
  • 71 Walter U, Eigenthaler M, Geiger J. et al. Role of cyclic nucleotide-dependent protein kinases and their common substrate VASP in the regulation of human platelets. Adv Exp Med Biol 1993; 344: 237-249.
    PubMedGoogle Scholar
  • 72 Wiedmer T, Shattil SJ, Cunningham M. et al. Role of calcium and calpain in complement-induced vesiculation of the platelet plasma membrane and in the exposure of the platelet factor Va receptor. Biochemistry 1990; 29: 623-632.
    CrossrefPubMedGoogle Scholar