Clopidogrel is one of several widely prescribed antiplatelet medications, used to prevent thrombosis (blood clots) in arteries and arterioles. A common reason for long-term treatment with clopidogrel, often in combination with low-dose aspirin, is risk reduction for stroke and cardiovascular diseases.  

Figure 1: The molecular structure of clopidogrel (highlighted), together with the molecular structures of the closely related medications prasugrel and ticagrelor.

Clopidogrel as depicted in Figure 1 is a pro-drug that first needs to be converted to its active form once administered. This chemical conversion of clopidogrel (an oxidation reaction) requires the action of a number of liver enzymes. Accordingly, clopidogrel should not be the first choice of antiplatelet medication for people with reduced liver function. Also, a type of widely used antacid medications (proton pump inhibitors, which suppress the production of stomach acid) reduce the antiplatelet activity of clopidogrel.

Once clopidogrel is converted to its active metabolite by several liver enzymes, the active metabolite irreversibly blocks a receptor (a protein, P2Y12) that is found on the surface of platelets. P2Y12 is an important regulator protein in the cascade of reactions leading to blood clotting. Blocking P2Y12 prevents the aggregation of platelets and thus the subsequent formation of a blood clot. The resulting, most prominent adverse effect of clopidogrel (and other antiplatelet medications) is a tendency for excessive bleeding. The overall effects of prasugrel and ticagrelor are similar to those of clopidogrel, as all three drugs block the P2Y12 receptors on the platelet surface. However, there are some subtle but significant differences in the underlying biochemical mechanisms.

A tendency for excessive bleeding is obviously relevant for any oral and maxillofacial surgical interventions. As the effect of a dose of clopidogrel persists for several days, wherever possible careful consideration needs to be given to modification of antiplatelet medication ahead of surgical interventions if excessive bleeding is a risk. This is possible for many elective procedures but obviously is not an option for trauma and other emergency situations leading to blood loss.