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 antiinflammatory actions. Low-dose aspirin is used in the management of cardiovascular events (e.g., acute MI) and for primary/secondary prophylaxis of cardiovascular disease. Adverse effects of aspirin include peptic ulcers, hemorrhage, salicylate toxicity, aspirin-exacerbated respiratory disease, and Reye syndrome. 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 stent thrombosis in patients after percutaneous coronary intervention (PCI). 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 usually contraindicated in patients who have thrombocytopenia or active/recent bleeding (e.g., hemorrhagic stroke, major surgery within the past 30 days).
|Overview of antiplatelet agents|
Irreversible cyclooxygenase inhibitors
Mechanism of action 
ASA covalently attaches an acetyl group to COX.
Irreversible COX-1 inhibition → inhibition of thromboxane (TXA2) synthesis in platelets → inhibition of platelet aggregation (antithrombotic effect)
- Onset of antiplatelet action: within minutes
- Duration of antiplatelet action: 7–10 days
- Irreversible COX-1 and COX-2 inhibition → inhibition of prostacyclin and prostaglandin synthesis → antipyretic, anti-inflammatory, and analgesic effect
- Low dose (below 300 mg/day): inhibition of platelet aggregation
- Intermediate dose (300-2400 mg/day): antipyretic and analgesic effect
- High dose (2400-4000 mg/day): antiinflammatory effect
- Acute ischemic stroke 
- Angina (stable and unstable)
- Secondary prevention of CVD
- Primary prevention of CVD and colorectal cancer 
- Prevention of stent thrombosis after revascularization procedures (e.g., PTCA, CABG, carotid endarterectomy)
- See “pain management and inflammation. ” for indications in
Gastrointestinal (most common): aspirin blocks COX-1 → inhibition of conversion arachidonic acid to PGH2 → ↓ formation of PGE2 ; → ↓ secretion of mucus and bicarbonate by epithelium → loss of protective layer on mucosa → gastric acid damages tissue → ↑ risk of ulcers, bleeding, and perforation
- Gastric ulceration, hemorrhage, perforation
- Coagulopathy and bleeding: These effects continue until new platelets are formed.
- Tinnitus: aspirin affects the vestibulocochlear nerve
- Renal (in the case of long-term use)
- Salicylate poisoning: See “ .
- Cutaneous reactions
- Anaphylactoid reactions
- Febrile illness in individuals < 19 years of age
- Acute gout attack 
Aspirin-exacerbated respiratory disease (AERD) 
- Etiology: imbalance between proinflammatory leukotrienes and antiinflammatory prostaglandins resulting from COX enzyme inhibition
- Clinical features: Samter triad (asthma, chronic/recurrent rhinosinusitis, nasal polyps)
Reye syndrome 
- Description: a rare type of hepatic encephalopathy that is associated with aspirin use for viral illness in children < 19 years
- Etiology: aspirin use in individuals < 19 years of age with a febrile illness 
- Viruses alter the metabolism of salicylates → accumulation of salicylate metabolites in the liver → mitochondrial injury and reversible inhibition of enzymes required for fatty acid oxidation; → failure of hepatic ATP production → → hyperammonemia, metabolic acidosis, and hepatic steatosis → acute encephalopathy
- Hyperammonemia → cerebral edema → ↑ ICP
- Preceding viral infection (e.g., influenza, varicella or viral gastroenteritis): The first symptoms of Reye syndrome usually begin 3–5 days after a viral illness.
- Acute encephalopathy
- Fatty degeneration
- Diagnostics: clinical diagnosis; further testing to rule out other causes (diagnosis of exclusion)
- Treatment: supportive
- Outcomes vary from complete recovery to permanent neurological deficits.
- Mortality rate: ∼ 20% 
To memorize the symptoms of Reye syndrome, remember that “It’s never Rainy () in CHILE”: Coma, Hepatomegaly/Hypoglycemia, history of viral Infection, Liver failure, Encephalopathy.
- Faster acting and more potent than clopidogrel
- Ticlopidine: irreversible P2Y12 receptor antagonist
- Cangrelor: IV administered P2Y12 receptor antagonist
Mechanism of action
- Inhibition of P2Y12 receptor on platelets (ADP receptor) → ↓ expression of Gp IIb/IIIa receptors on platelets → inhibition of platelet aggregation
- Dual antiplatelet therapy (in combination with acetylsalicylic acid)
- Alternative to aspirin in cases of intolerance: to prevent recurrence of thromboembolic events, including ischemic stroke, MI, and symptomatic peripheral arterial disease
- Abciximab (monoclonal antibodies against ) fragments of
- Tirofiban 
Mechanism of action 
- Gp IIb/IIIa inhibitors bind to and block glycoprotein IIb/IIIa receptors (fibrinogen receptor) on the surface of activated platelets → prevention of platelets binding to fibrinogen; → inhibition of platelet aggregation and thrombus formation
- Prevention of thrombotic complications in high-risk patients with unstable angina/NSTEMI planned for PCI within 24 hours
- Acute profound thrombocytopenia
To remember that ABCiximab targets glycoproteins IIb/IIIa, think ABC rhymes with 123!
Eptifibatide and tirofiban are fibrinogen receptor blockers.