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.