Thromb Haemost 2000; 84(06): 1109-1112
DOI: 10.1055/s-0037-1614178
Review Article
Schattauer GmbH

Effect of Sodium Arachidonate on Thrombin Generation through Platelet Activation – Inhibitory Effect of Aspirin

Raul Altman
2   From Centro de Trombosis de Buenos Aires, Buenos Aires, Argentina
,
Alejandra Scazziota
2   From Centro de Trombosis de Buenos Aires, Buenos Aires, Argentina
,
Jorge Rouvier
2   From Centro de Trombosis de Buenos Aires, Buenos Aires, Argentina
,
Claudio Gonzalez
1   Department of Pharmacology, School of Medicine, University of Buenos Aires, Argentina
› Author Affiliations
To Fundacion Rene Baron for supporting style correction of this paper.
Further Information

Publication History

Received 25 February 2000

Accepted after revision 07 June 2000

Publication Date:
13 December 2017 (online)

Summary

Background. Sodium arachidonate was used in this study to determine its capacity to generate thrombin through platelet activation. Whether aspirin prevent this effect was also investigated. Methods and Results. Seventeen healthy volunteers without and after 160 mg/day aspirin intake for 3-5 days were studied. Lag-time and TG at basal condition and after platelet stimulation by sodium arachidonate (AA) were measured in normal non-aspirinated as well as “in vivo” aspirinated platelet rich plasma. (PRP). The lag-time was statistically significant shorter in non-aspirinated PRP activated with AA compared with non-activated PRP. This effect was inhibited by aspirin. In non-aspirinated PRP, there was an increase of TG at 4 and 6 min. incubation when platelets were activated with AA but the difference disappeared after 8 min. incubation, (84 ± 71; 148 ± 58 and 142 ± 92 nmol/L respectively) compared with non-aspirinated, non-activated platelets (16 ± 23; 55 ± 56 and 111 ± 76 nmol/L at 4, 6 and 8 min, p < 0.0001, p < 0.0001 and p = 0.292, respectively). The AUCo→22 min were 520.6 ± 545.5 in nonaspirinated, non-stimulated PRP and 808.9 ± 617, in non-aspirinated PRP activated with sodium arachidonate (p = 0.014). Aspirin administered in vivo produced a decrease of TG in PRP activated with AA.

Conclusion. Platelet activated by AA trigged TG. This effect was inhibited by aspirin and could be an additional beneficial effect of aspirin in the prevention of thrombosis.

 
  • References

  • 1 Wilson JM, Ferguson III JJ. Platelet-endothelial interactions in atherothrombotic disease: Therapeutic implications. Clin Cardiol 1999; 22: 687-98.
  • 2 Hennekens CH, Dyken ML, Fuster V. Aspirin as a therapeutic agent in cardiovascular disease A statement for healthcare professionals from the American Heart Association. Circulation 1997; 96: 2751-3.
  • 3 Anti-platelet Trialistsc Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet therapy. Br Med J 1988; 296: 320-31.
  • 4 Goldstein RE, Andrews M, Hall J, Moss AJ. for the Multicenter Myocardial Research Group. Marked reduction in long-term cardiac deaths with aspirin after a coronary event. J Am Coll Cardiol 1996; 28: 326-30.
  • 5 Marcus AJ, Broekman MJ, Weksler BB, Jaffe EA, Safier LB, Ullman HL, Tack-Goldman K. Platelet, endothelial cells, and the thrombotic process. In: Herman AG, Vanhoutte PM, Denolin H, Goossens A. ed. Cardiovascular Pharmacology of the Prostaglandins. Raven Press; New York: 1982: 125-35.
  • 6 Kessels H, Béguin S, Andree H, Hemker HC. Measurement of thrombin generation in whole blood The effect of heparin and aspirin. Thromb Haemost 1994; 72: 78-83.
  • 7 Ammar T, Scudder LE, Coller BS. In vitro effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time. Circulation 1997; 95: 614-7.
  • 8 Reverter JC, Béguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody: Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis”. J Clin Invest 1996; 98: 863-74.
  • 9 Herault JP, Dol F, Gaich C, Bernat A, Herbert JM. Effect of clopidogrel on thrombin generation in platelet-rich plasma in the rat. Thromb Haemost 1999; 81: 957-60.
  • 10 Ross R. Atherosclerosis – An inflammatory disease. N Eng J Med 1999; 340: 115-26.
  • 11 Béguin S, Lindhout T, Hemker HC. The effect of trace amount of tissue factor on thrombin generation in platelet rich plasma, its inhibition by heparin. Thromb Haemost 1989; 61: 25-32.
  • 12 Hemker BC, Wielders SJH, Kessls H, Béguin S. Continuos registration of thrombin generation in plasma Its use for the determination of thrombin potential. Thromb Haemost 1993; 70: 617-24.
  • 13 Peyrou V, Lormeau JC, Herault JP, Gaich C, Pfliegger AM, Herbert JM. Contribution of erythrocytes to thrombin generation in whole blood. Thromb Haemost 1999; 81: 400-6.
  • 14 Conover WJ, Iman RL. Rank transformations as a bridge between parametric and non-parametric statistics. American Statistician 1981; 35: 124-33.
  • 15 Wallen NH, Ladjevardi M. Influence of low- and high-dose aspirin treatment on thrombin generation in whole blood. Thromb Res 1998; 92: 189-94.
  • 16 Musial J, Radman J, Szczeklik A. Aspirin delays thrombin generation in vitro through interaction with platelets phospholipids. Thromb Res 1996; 83: 329-38.
  • 17 Prasa D, Svendsen L, Sturzebecher J. The ability of thrombin inhibitors to reduce the thrombin activity generated in plasma on extrinsic and intrinsic activation. Thromb Haemost 1997; 77: 498-503.
  • 18 Rota S, Flynn PD, Wareham NJ, Baglin TP, Byme CD. Is platelet phospholipid-dependent thrombin generation altered by acute myocardial infarction or aspirin?. Thromb Res 1996; 83: 329-38.