Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions
Open Access
- 5 December 2006
- journal article
- review article
- Published by American Society of Hematology in Blood
- Vol. 109 (6), 2285-2292
- https://doi.org/10.1182/blood-2006-01-010645
Abstract
Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thrombin generation with the subsequent attenuation of thrombin-mediated coagulant reactions such as factor XIII activation. Aspirin also acetylates lysine residues in fibrinogen resulting in increased fibrin clot permeability and enhanced clot lysis as well as directly promoting fibrinolysis with high-dose aspirin. The variable effectiveness of aspirin in terms of clinical outcomes and laboratory findings, which has been termed aspirin resistance, may be related to these additional antithrombotic effects that are altered when associated with common genetic polymorphisms such as the Leu33Pro β3-integrin or Val34Leu factor XIII mutations. However, the clinical relevance of these observations is still unclear. Elucidation of the actual impacts of aspirin other than antiaggregation effects could be important in view of the widespread use of this drug in the prevention of thrombotic manifestations of atherosclerosis.Keywords
This publication has 111 references indexed in Scilit:
- Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunitiesJCI Insight, 2005
- Aspirin resistance and a single geneThe American Journal of Cardiology, 2005
- Biological Assessment of Aspirin Efficacy on Healthy IndividualsStroke, 2005
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patientsBMJ, 2002
- Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphismBritish Journal of Haematology, 1997
- Development of aspirin resistance in persons with previous ischemic stroke.Stroke, 1994
- Expression of mRNA for cyclooxygenase‐1 and cyclooxygenase‐2 in human tissuesFEBS Letters, 1993
- Acetylation of Antithrombin III by AspirinSeminars in Thrombosis and Hemostasis, 1986
- Dose-Related Kinetics of AspirinThe New England Journal of Medicine, 1984
- Arachidonic Acid Metabolites and the Interactions between Platelets and Blood-Vessel WallsThe New England Journal of Medicine, 1979