The biologic background to some therapeutic uses of aspirin

The therapeutic success of aspirin as an effective analgesic, antipyretic, and anti-inflammatory drug had been universally established for many decades before its mode of action was discovered in 1971. This mode of action is the prevention, or diminution, of prostaglandin biosynthesis through the inhibition of the enzyme, cyclo-oxygenase. Demonstrations of the major contributions of prostaglandins to pain, fever, and other cardinal features of inflammation provided rational explanations for the well-established therapeutic uses of aspirin. It had been shown earlier that aspirin antagonized two mediators of inflammation by an indirect process. While aspirin's mode of action was being discovered, research on platelets in hemostasis and thrombosis was also being done. It was shown that aspirin inhibited an exocytotic reaction (the release reaction) of platelets. This reaction was regarded as essential for their aggregation as thrombi in, most importantly, coronary and cerebral arteries. This observation was the starting point of an enormous effort, still going on to determine through both fundamental and clinical investigations, the therapeutic potential of aspirin as an antithrombotic drug. Costly clinical trials have provided evidence in favor of aspirin preventing thrombotic events affecting the brain; its effectiveness against coronary thrombosis is not yet definitely established. Possible explanations for this situation will be considered on the basis of rapidly advancing biologic knowledge about the mechanism of thrombosis.