High‐Dose Aspirin Inhibits Shear‐Induced Platelet Reaction Involving Thrombin Generation

BackgroundA unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions. Methods and ResultsTwo hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p<0.0001 versus <0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; <0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction. ConclusionsIt is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (>300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.

[1]  I. Kovács,et al.  Coagulation of flowing native blood: advantages over stagnant (tube) clotting tests. , 1991, Thrombosis research.

[2]  V. Fischetti,et al.  Streptococcal M protein. , 1991, Scientific American.

[3]  V. Gebski,et al.  Immediate Postoperative Aspirin Improves Vein Graft Patency Early and Late After Coronary Artery Bypass Graft Surgery: A Placebo‐Controlled, Randomized Study , 1991, Circulation.

[4]  I. Kovács,et al.  Infusion of a stable prostacyclin analogue, iloprost, to patients with peripheral vascular disease: lack of antiplatelet effect but risk of thromboembolism. , 1991, The American journal of medicine.

[5]  W J Penny,et al.  Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis. , 1990, Circulation.

[6]  J. O'brien,et al.  Shear-induced platelet aggregation , 1990, The Lancet.

[7]  I. Kovács,et al.  Modelling coronary thrombosis from nonanticoagulated human blood in vitro. , 1990, Hematologic pathology.

[8]  P. Lumley,et al.  Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. , 1990, Circulation.

[9]  N. Arber,et al.  Platelet hyperreactivity and prognosis in survivors of myocardial infarction. , 1990, The New England journal of medicine.

[10]  H. Gold,et al.  Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition. , 1990, Circulation.

[11]  A. Svindland,et al.  Pathogenesis of carotid thrombosis. , 1989, Stroke.

[12]  R. Collins,et al.  Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. , 1989, Circulation.

[13]  N. Peters,et al.  Platelet hyperreactivity and inefficient spontaneous thrombolysis in patients at high risk from an acute coronary event. , 1989, Cardiovascular research.

[14]  Janice,et al.  Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. , 1989, The Journal of clinical investigation.

[15]  F. Verheugt,et al.  Effect of low dose acetylsalicylic acid on the frequency and hematologic activity of left ventricular thrombus in anterior wall acute myocardial infarction. , 1989, The American journal of cardiology.

[16]  I. Kovács,et al.  Hemostatic evaluation in bleeding disorders from native blood. Clinical experience with the hemostatometer. , 1989, American journal of clinical pathology.

[17]  E. Minar,et al.  Lack of influence of low-dose acetylsalicylic acid (100 mg daily) on platelet survival time, beta-thromboglobulin and platelet factor 4 in patients with peripheral arterial occlusive disease. , 1988, Thrombosis research.

[18]  P. Sørensen,et al.  Danish very-low-dose aspirin after carotid endarterectomy trial. , 1988, Stroke.

[19]  J. Moake,et al.  Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin , 1988 .

[20]  J D Hellums,et al.  Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin. , 1988, Blood.

[21]  R. Kinlough-Rathbone,et al.  Thromboxane A2 causes feedback amplification involving extensive thromboxane A2 formation on close contact of human platelets in media with a low concentration of ionized calcium , 1987 .

[22]  H. Eichler,et al.  Inhibition of prostacyclin and thromboxane A2 generation by low-dose aspirin at the site of plug formation in man in vivo. , 1987, Circulation.

[23]  J. Mustard,et al.  Thromboxane A2 causes feedback amplification involving extensive thromboxane A2 formation on close contact of human platelets in media with a low concentration of ionized calcium. , 1987, Blood.

[24]  H. Gralnick,et al.  Identification of platelet glycoprotein IIb/IIIa as the major binding site for released platelet-von Willebrand factor. , 1986, Blood.

[25]  Acetylation of antithrombin III by aspirin. , 1986, Seminars in thrombosis and hemostasis.

[26]  G. Angelini,et al.  IS THERE A RATIONALE FOR TREATMENT WITH ASPIRIN BEFORE CORONARY SURGERY? , 1985, The Lancet.

[27]  H Schmid-Schönbein,et al.  Platelet and Coagulation Parameters Following Millisecond Exposure to Laminar Shear Stress , 1985, Thrombosis and Haemostasis.

[28]  G. FitzGerald,et al.  Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. , 1983, The Journal of clinical investigation.

[29]  J. Mehta,et al.  Platelet aggregation. , 1983, Blood.

[30]  C. Patrono,et al.  Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. , 1982, The Journal of clinical investigation.

[31]  J. Hirsh,et al.  Aspirin inhibits platelet function independent of the acetylation of cyclo-oxygenase. , 1982, Thrombosis research.

[32]  J. Vane,et al.  Prostacyclin: its biosynthesis, actions, and clinical potential. , 1981, Advances in prostaglandin, thromboxane, and leukotriene research.

[33]  J. Vane,et al.  Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. , 1971, Nature: New biology.

[34]  L. Aledort,et al.  Impaired platelet-connective-tissue reaction in man after aspirin ingestion. , 1967, Lancet.