Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions.
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 A(2) 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 A(2) 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 beta(3)-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.
Undas
Anetta
A
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland.
Brummel-Ziedins
Kathleen E
KE
Mann
Kenneth G
KG
D001241:Aspirin / Q000494:pharmacology*; D004351:Drug Resistance; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D013917:Thrombin; D001241:Aspirin