Recently, during my cardiology rotation, I had to face the troublesome anticoagulant and antiplatelet drugs again. This time, with both clinical cases and Liu Zhongbao’s physiology, I reviewed everything from physiology to clinical applications in internal medicine. Today, I finally understood antiplatelet drugs and would like to share.
Platelet Aggregation Process
First, a review of the physiological process of platelet aggregation
- Adhesion: When blood vessel endothelium is damaged and collagen fibers are exposed, platelets adhere to the collagen fibers, adsorbing coagulation factors (providing a phospholipid surface work site for coagulation factors), promoting the formation of prothrombin activator — resulting in a soft thrombus.
- Aggregation: Platelets aggregate by adhering to each other to form aggregates (white thrombus).
- Release: Platelets release factors that promote fibrin formation, creating a network of blood cells — expanding the thrombus.
- Through COX synthesis of [[Thromboxane A2]], which can be inhibited by cyclooxygenase inhibitors.
- Release of ADP already present inside platelets (an endogenous aggregating agent), which can be inhibited by P_2Y_{12} receptor antagonists.
- Contraction: Under the action of Ca2+, internal proteins contract, causing clot retraction — forming a firm thrombus.
Two pathways inhibit platelet factors, thereby inhibiting coagulation.
Cyclooxygenase Inhibitors
By inhibiting COX activity, the synthesis of thromboxane A2 (TXA2) is blocked, achieving antiplatelet aggregation effects. This includes irreversible COX inhibitors (aspirin) and reversible COX inhibitors (indobufen).
- Aspirin is the cornerstone of antiplatelet therapy. All patients without contraindications should use it, with an optimal dose range of 75~150mg/day. The main adverse reactions are gastrointestinal bleeding or aspirin allergy.
- Indobufen reversibly inhibits COX-1, while reducing platelet factors 3 and 4, decreasing platelet aggregation. It has low inhibition of prostaglandins, mild gastrointestinal reactions, and low bleeding risk. It can be considered as an alternative treatment for patients intolerant to aspirin due to gastrointestinal bleeding or digestive tract ulcers. The maintenance dose is 100mg twice daily.
P2Y12 Receptor Antagonists
They inhibit ADP-induced platelet activation by blocking platelet P_2Y_{12} receptors. Currently, the commonly used P_2Y_{12} receptor antagonists in clinical practice in China are clopidogrel and ticagrelor. Stable coronary artery disease patients mainly use clopidogrel.
- Clopidogrel: A second-generation P2Y12 receptor antagonist. It is a prodrug that requires metabolism by hepatic cytochrome P450 (CYP450) enzymes into an active metabolite, which irreversibly inhibits the P_2Y_{12} receptor, thus inhibiting platelet aggregation. It is mainly used after stent implantation and for patients with aspirin contraindications. The usual maintenance dose is 75mg daily.
- Ticagrelor: If a patient has hepatic dysfunction and cannot metabolize clopidogrel normally into its active form, switching to ticagrelor is required.
- For more questions about clopidogrel and ticagrelor, see 氯吡格雷、替格瑞洛及CYP2C19、CYP3A4药理与代谢
References
Liu Zhongbao Physiology 西医老师安利——刘忠保
People’s Medical Publishing House Internal Medicine 9th Edition