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Thromb Haemost 2001; 85(06): 1097-1103
DOI: 10.1055/s-0037-1615972
Review Article
Schattauer GmbH

The Effect of Platelet PlA Polymorphism on Experimental Thrombus Formation in Man Depends on Blood Flow and Thrombogenic Substrate

Yves Cadroy
1   Laboratoire de Recherche sur l’Hémostase et la Thrombose, CHU Purpan, Toulouse, France
,
Kjell Sakariassen
2   Department of Biology, Division of General Physiology, University of Oslo, Oslo, Norway
,
Hélène Grandjean
3   INSERM, Hôpital La Grave, Toulouse
,
Claire Thalamas
4   Centre d’Investigation Clinique, CHU Purpan, Toulouse, France
,
Bernard Boneu
1   Laboratoire de Recherche sur l’Hémostase et la Thrombose, CHU Purpan, Toulouse, France
,
Pierre Sié
1   Laboratoire de Recherche sur l’Hémostase et la Thrombose, CHU Purpan, Toulouse, France
› Author Affiliations
Further Information

Publication History

Received 13 November 2000

Accepted after resubmission 06 February 2001

Publication Date:
12 December 2017 (online)

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Summary

A number of studies have reported conflicting data on the association of the PlA1/PlA2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thrombus formation in man. Forty healthy male volunteers were genotyped for the PlA1/PlA2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagencoated coverslip in a parallel plate perfusion chamber to native blood for 2 and 4 min. The shear rates at these surfaces were 650 and 2,600 s–1. Platelet and fibrin deposition was quantified by immunoenzymatic methods. The frequencies of PlA1/PlA1 and PlA1/PlA2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the PlA1/PlA2 polymorphism. However, the ex vivo platelet deposition at 650 s–1 was higher in blood from PlA1/PlA1 individuals than in PlA1/PlA2 individuals (P = 0.008 at 4 min). On collagen, neither fibrin nor platelet deposition was significantly affected by the PlA1/PlA2 polymorphism. Platelet thrombus formation is significantly influenced by genetic variations in the GPIIIa platelet receptor. This effect depends on the blood flow properties and the nature of the thrombogenic stimulus.

Key words

Blood flow - genes - platelets - risk factors - thrombosis
 

  • References

  • 1 Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989; 83: 1778-81.
    CrossrefPubMedGoogle Scholar
  • 2 Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
    CrossrefPubMedGoogle Scholar
  • 3 Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 2000; 95: 1517-32.
    PubMedGoogle Scholar
  • 4 Feng D, Lindpaintner K, Larson MG, Rao VS, O’Donnell CJ, Lipinska I, Scmitz C, Sutherland PA, Silbershatz H, D’Agostino RB, Muller JE, Myers RH, Levy D, Tofler GH. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism. The Framingham offspring study. Arterioscler Thromb Vasc Biol 1999; 19: 1142-7.
    CrossrefPubMedGoogle Scholar
  • 5 Michelson AD, Furman MI, Goldschmidt-Clermont P, Mascelli MA, Hendrix C, Coleman L, Hamlington J, Barnard MR, Kickler T, Christie DJ, Kundu S, Bray PF. Platelet GP, III a PlA polymorphisms display different sensitivities to agonists. Circulation 2000; 101: 1013-8.
    CrossrefPubMedGoogle Scholar
  • 6 Corral J, Gonzalez-Conejero R, Rivera J, Iniesta JA, Lozano ML, Vicente V. HPA-1 genotype in arterial thrombosis. Role of HPA-1b polymorphism in platelet function. Blood Coag Fibrinolyis 1997; 8: 284-90.
    PubMedGoogle Scholar
  • 7 Lasne D, Krenn M, Pingault V, Arnaud E, Fiessenger JN, Aiach M, Rendu F. Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphism. Br J Haematol 1997; 99: 801-7.
    CrossrefPubMedGoogle Scholar
  • 8 Goodall AH, Curzen N, Panesar M, Hurd C, Knight CJ, Ouwehand WH, Fox KM. Increased binding of fibrinogen to glycoprotein IIIa-Proline 33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease. Eur Heart J 1998; 20: 742-7.
    PubMedGoogle Scholar
  • 9 Meiklejohn DJ, Urbaniak SJ, Greaves M. Platelet glycoprotein IIIa polymorphism HPA 1b (PlA2): no association with platelet fibrinogen binding. Br J Haematol 1999; 105: 664-6.
    CrossrefPubMedGoogle Scholar
  • 10 Vijayan KV, Goldschmidt-Clermont PJ, Roos C, Bray PF. The PlA2 polymorphism of integrin β3 enhances outside-in signaling and adhesive functions. J Clin Invest 2000; 105: 793-802.
    CrossrefPubMedGoogle Scholar
  • 11 Cadroy Y, Bossavy JP, Thalamas C, Sagnard L, Sakariassen KS, Boneu B. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in man. Circulation 2000; 101: 2823-8.
    CrossrefPubMedGoogle Scholar
  • 12 van Zanten GH, de Graaf S, Slootweg PJ, Heijnen HFG, Connolly TM, de Groot PG, Sixma JJ. Increased platelet deposition on atherosclerotic coronary arteries. J Clin Invest 1994; 93: 615-32.
    CrossrefPubMedGoogle Scholar
  • 13 Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez-Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-9.
    CrossrefPubMedGoogle Scholar
  • 14 Miller SA, Dwikes DD, Polesky HF. A simple salting out procedure for extracting DNA from nucleated cells. Nucleic Acids Res 1988; 16: 1215.
    CrossrefPubMedGoogle Scholar
  • 15 Fressinaud E, Veyradier A, Truchaud F, Martin I, Boyer-Neumann C, Trossaert M, Meyer D. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood 1998; 91: 1325-31.
    PubMedGoogle Scholar
  • 16 Undas A, Sanak M, Musial J, Szczeklik A. Platelet glycoprotein IIIa polymorphism, aspirin and thrombin generation. Lancet 1999; 353: 982-3.
    CrossrefPubMedGoogle Scholar
  • 17 Orvim U, Roald HE, Stephens RW, Ross N, Sakariassen KS. Tissue factor-induced coagulation triggers platelet thrombus formation as efficiently as fibrillar collagen at arterial blood flow conditions. Arterioscler Thromb 1994; 14: 1976-83.
    CrossrefPubMedGoogle Scholar
  • 18 Andrioli G, Minuz P, Solero P, Pincelli S, Ortolani R, Lussignoli S, Bellavite P. Defective platelet response to arachidonic acid and thromboxane A2 in subjects with PlA2 polymorphism of β3 subunit (glycoprotein IIIa). Br J Haematol 2000; 110: 911-8.
    CrossrefPubMedGoogle Scholar
  • 19 Weiss HJ, Turitto VT, Vicic WJ, Baumgartner HR. Effect of aspirin and dipyridamole on the interaction of human platelets with sub-endothelium: studies using citrated and native blood. Thromb Haemost 1981; 45: 136-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood 1998; 91: 2645-57.
    PubMedGoogle Scholar
  • 21 Gardemann A, Humme J, Sticker J, Nguyen QD, Katz N, Philipp M, Tillmans H, Hehrlein FW, Rau M, Haberbosch W. Association of the platelet glycoprotein IIIa PlA1/A2 gene polymorphism to coronary artery disease but not to nonfatal myocardial infarction in low risk patients. Thromb Haemost 1998; 80: 214-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Von der Borne AEG, Decary F. Nomenclature of platelet specific antigen. Transfusion 1990; 30: 477-81.
    PubMedGoogle Scholar
  • 23 Kim HO, Jin Y, Kickler TS, Blakemore K, Kwon OH, Bray PF. Gene frequencies of the five major human platelet antigens in African American, white and Korean populations. Transfusion 1995; 35: 963-7.
    PubMedGoogle Scholar