Aspirin Resistance: Molecular Mechanisms & Techniques

Aspirin became a cornerstone in the treatment of coronary artery disease and widely used in the secondary prevention of vascular events. Aspirin resistance remains a poorly defined term though clinical definition is failure of the drug to prevent an atherothrombotic event despite the regular intake of appropriate doses is a relatively common problem. Various laboratory parameters assessing its efficacy, like bleeding time, platelet reactivity, thromboxane A2 (TXA2) production and measurement of platelet aggregation have confirmed the lack of its uniform effect on the platelets. Various molecular mechanism responsible for Aspirin resistance include Insufficient suppression of COX-1, overexpression of COX-2 mRNA, Erythrocyte induced platelet activation, Genetic polymorphism of enzymes like COX-1, COX-2 or thromboxane A2 synthase. Clinical factor like non compliance of patient is also responsible for Aspirin resistance. The limitations in understanding Aspirin resistance include difficulties in assessing platelet function and aspirin resistance and contributed to variable reporting of Aspirin resistance. Therefore, the definition of Aspirin resistance requires refinement to include genetic polymorphism of various enzymes responsible for Aspirin resistance. However, various techniques for platelet analysis also require modification to understand Aspirin resistance. INTRODUCTION: ASA (Acetyl salicylic acid) more commonly known as aspirin is one of the oldest medications still in wide availability. Early Hippocrates used willow leaves, rich in ASA, to relieve the aches associated with multiple illnesses in ancient Greece . Reverend Edmund Stone isolated salicilin, the glycoside of salicylic acid and the active ingredient of aspirin, from the bark of a willow tree in England in 1763 . This ‘newly’ discovered compound was named for the Salix Alba, literally white willow. In the 1800s, various scientists tried for the extraction of salicylic acid from willow bark, but it was not until 1897 that Felix Hoffmann, a German chemist working for Friedrich Bayer has developed a well-tolerated compound and ASA was born . Bayer marketed aspirin in 1899 and dominated the flourishing market of pain relievers . Since then, aspirin has grown to become one of the most commonly identified trade names around the globe and one of the most commercially successful drugs. In the modern medical literature, the antithrombotic effects of aspirin were first reported in the Mississippi Valley Medical Journal in 1953 . Since then, numerous studies have confirmed aspirin’s antiplatelet effect, establishing its therapeutic efficacy and validating its widespread use . Aspirin has become a cornerstone in the treatment of coronary artery disease (CAD) . The beneficial role of aspirin in the secondary prevention of vascular events is now well established 6, .