As Leonard sits in the back of your ambulance, you ask him to describe his chest pain. He looks at you with small droplets of cold sweat on his forehead and says: " It feels... like .....someone.... is sitting on my chest." Your partner hands you four baby aspirin and you ask the patient to open up his mouth and chew these aspirin before swallowing. Your patient tells you he already took two baby aspirin before you arrived. Your protocols state the patient must receive 324mg. You stop for a second and wonder where the evidence for this dose came from.
How Does Aspirin Work?
As a non-selective cyclooxygenase (cox) inhibitor, acetylsalicylic acid (ASA) works by blocking the enzyme that leads to specific prostaglandins. For all intents and purposes, think of prostaglandins like little tattle tells in the body. They are signals that tell the body something bigger needs to happen.This could be clot formation, inflammation, or telling you to take your hand off the stove by amplifying a pain signal.
At smaller doses (0.45mg/kg), ASA will primarily effect deactivation of cox 1 hormones such as thromboxane a2 (hemostasis) and prostaglandin I2 (stomach mucosal defense). Larger doses are needed to inhibit cox 2 prostaglandin synthesis.
Think of cox 1 as physiological signals (platelet aggregation or stomach mucosal production)
Think of cox 2 as inducible signals (pain or inflammation)
As the endothelial wall of a vessel is damaged, the platelets which ride against its surface will release arachidonic acid from the phospholipid membrane (via phospholipase blah blah blah I sound smart) of the platelet. The arachidonic acid will then be converted to hormones through the cox enzyme. One of these hormones that ASA inhibits is thromboxane a2.
Whenever there is trouble in the world of hemostasis, the platelets release thromboxane a2 to constrict vasculature and increase platelet aggregation at the site of endothelial disruption (things that don't help in ACS!).
This is like the bodies way of throwing on a tiny tourniquet and quick clot
Once ASA deactivates the cox enzyme within a platelet, the mechanism is irreversible for the remaining life of that cell (10ish days depending on if the cell does crossfit). With that being said, could we reason that the more aspirin we administer, the more platelets that will be effected? If so, do the benefits outweigh the risks associated with impaired hemostasis?
Let's Look At Some Lit!
Most of the evidence we see from the American Heart Association (AHA) recommending ASA comes from the ISIS-2 study that was published in the Lancet of 1988. This was a randomized controlled trial that looked at aspirin alone, streptokinase alone, aspirin with streptokinase, and a control. The mortality at five weeks showed a statistical significant decrease in vascular death in both intervention groups (23% mortality reduction in ASA group P
Original author: Tyler Christifulli
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