• Clinical science

Antiplatelet agents

Abstract

Antiplatelet agents are drugs that inhibit enzymes or receptors required for platelet activation, platelet aggregation, and/or thrombus formation. The most commonly used antiplatelet agent is acetylsalicylic acid (aspirin), which is an irreversible cyclooxygenase inhibitor with dose-dependent antiplatelet, antipyretic, analgesic, and anti-inflammatory actions. Low-dose aspirin is used in the management of cardiovascular events (e.g., acute MI, angina) and for primary/secondary prophylaxis of cardiovascular disease. Adverse effects of aspirin include peptic ulcers, hemorrhage, aspirin-exacerbated respiratory disease, and Reye syndrome. Aspirin overdose (salicylate toxicity) presents with tinnitus, tachypnea, vomiting, and a characteristic mixed respiratory alkalosis and metabolic acidosis on ABG. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) are mainly used in conjunction with aspirin (dual antiplatelet therapy) in the management of acute coronary syndrome and to prevent rethrombosis in patients after percutaneous coronary intervention (PCI) and/or stenting. Although allergic reactions are more common, P2Y12 receptor antagonists cause fewer hemorrhagic/gastrointestinal complications compared to aspirin. Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) are parenterally administered, rapid-acting antiplatelet agents that are only used in high-risk patients in which PCI is planned. Gp IIb/IIIa inhibitors can cause a sudden drop in platelet counts (acute profound thrombocytopenia), necessitating platelet count monitoring. All antiplatelet agents increase the risk of hemorrhage and are contraindicated in patients who have thrombocytopenia or an active/recent hemorrhagic event (e.g., hemorrhagic stroke, major surgery within the past 30 days).

Overview

For the mechanisms of platelet activation, platelet adhesion, platelet aggregation, and clot formation, see “Pathophysiology” in the learning card hemostasis and bleeding disorders.

Group

Agents

Indications

Side effects

Irreversible cyclooxgenase inhibitors

P2Y12 receptor antagonists

(ADP receptor inhibitors)

Glycoprotein IIb/IIIa inhibitors

References:[1][2]

Irreversible cyclooxygenase inhibitors

Agents
Effects
  • COX-1 inhibition → irreversible inhibition of thromboxane (TXA2) synthesis in plateletsinhibition of platelet aggregation (antithrombotic effect)
    • Onset of antiplatelet action: within minutes
    • Duration of antiplatelet action: 7–10 days
  • COX-1 and COX-2 inhibition → irreversible inhibition of prostacyclin and prostaglandin synthesis → antipyretic, anti-inflammatory, and analgesic effect
Indications
Side effects

Since the antiplatelet effect of aspirin persists for approx. one week, aspirin should be discontinued at least 7 days prior to surgery or invasive procedures to reduce the risk of bleeding!

Emergency inhibition of the antiplatelet effect of aspirin can only be achieved by administering platelet concentrates!
References:[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]

P2Y12 receptor antagonists

Agents
Effects
  • Inhibition of P2Y12 receptor on platelets (ADP receptor) → inhibition of platelet aggregation
    • ADP usually binds to P2Y12 receptors, leading to activation of Gp IIb/IIIa receptors and subsequent platelet aggregation.
Side effects
Indications
  • As dual antiplatelet therapy (in combination with acetylsalicylic acid)
  • As an alternative to aspirin in cases of intolerance
  • Cangrelor is indicated in patients who require a PCI and who have not and will not receive GP IIb/IIIa inhibitors.

References:[24][25][26][27][28][29][30]

Glycoprotein IIb/IIIa inhibitors

Agents
Effects
  • Gp IIb/IIIa inhibitors bind to and block glycoprotein IIb/IIIa receptors on the surface of the plateletsprevention of platelets binding to fibrinogen inhibition of platelet aggregation and thrombus formation
Side effects
Indications
  • Only indicated in high-risk patients with unstable angina/NSTEMI planned for PCI within 24 hours to prevent thrombotic complications (not for routine use)
  • In patients who have been started on Gp IIb/IIIa inhibitors who require CABG surgery, abciximab should be stopped at least 12 hours before surgery and eptifibatide/tirofiban should be stopped at least 4 hours before surgery to minimize the risk of bleeding.

Abciximab and tirofiban are contraindicated in patients with thrombocytyes < 100,000/mm3!

References:[31][32][33][34][35][36][37]

Contraindications

References:[33][38][39]

We list the most important contraindications. The selection is not exhaustive.