Contributors:Sam Gillespie, BSc, Robyn Hughes, MScBMC, Elizabeth Nixon-Shapiro, MSMI, CMI, Sean Watts, MD
Hemostasis is divided into primary hemostasis, where circulating cell fragments called platelets form a plug at the site of an injured blood vessel, and secondary hemostasis, which involves multiple coagulation factors working together to form a fibrin mesh to stabilize the platelet plug.
Endothelial injury is when the innermost layer of the artery, called the endothelium, gets damaged.
The second step is exposure, where the damaged endothelium exposes the underlying collagen.
The underlying collagen and endothelial cells then release a protein called Von Willebrand's factor, or vWF, that binds to this collagen.
This allows platelets to rapidly aggregate at the site of injury, and form a large platelet plug that can stop the bleeding. Now, antiplatelet medications interfere at different steps during this process.
Aspirin accomplishes this by irreversibly inhibiting the activity of cyclooxygenase enzymes, abbreviated COX-1 and COX-2, via acetylation.
This is where an acetyl group made up of two carbons, three hydrogens, and an oxygen is permanently attached to the enzyme.
When COX-1 and COX-2 get inhibited, thromboxane A2, which is a downstream product of the cyclooxygenase pathway can no longer be produced.
Aspirin, as an antiplatelet medication, gets used in a low dose form of 75-325 milligrams in several clinical situations to prevent clots from worsening.
Ticagrelor binds reversibly and in a non-competitive manner--meaning it binds to the receptor in an area outside of the active site where ADP normally binds. This decreases the receptors affinity for ADP, leading to decreased platelet activation.
The ADP receptor inhibitors are used in combination with aspirin for the treatment of acute coronary syndrome, which is a spectrum of symptoms that arise when there is limited blood flow to the heart.
They are also effective for preventing ischemic strokes and myocardial infarctions in people with atherosclerosis, and can be used inplace of aspirin if the person has an aspirin allergy. In fact, clopidogrel is considered equally effective as aspirin.
This is a procedure where blocked vessels in the heart are kept open using a tube shaped device.
In terms of toxicity, the ADP receptor inhibitors increase the risk of bleeding like other antiplatelet medications, but they can also cause a condition called thrombotic thrombocytopenic purpura, where microthrombi form in small blood vessels, causing ischemic damage to various organs.
The medication ticlopidine, is rarely used now, because it can cause a very serious condition called neutropenia, or low levels of a type of immune cell called neutrophils, and increases the risk of serious infections.
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