Submitted January 18, 2006
Accepted April 27, 2006
Antithrombotic properties of aspirin and resistance to
aspirin: beyond strictly antiplatelet actions
Anetta Undas, Kathleen E Brummel-Ziedins, and Kenneth G Mann*
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland
Dept of Biochemistry, University of Vermont, Colchester, VT, United States
* Corresponding author; email: kenneth.mann{at}uvm.edu.
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. There is also growing evidence 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 
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 anti-aggregatory effects could be important in view of the widespread use of this drug in the prevention of thrombotic manifestations of atherosclerosis.
