Organ transplantation and drug eluting stents: Perioperative challenges

Table 2 Antiplatelet drugs

Drug	Mechanism of action	Duration of action	Platelet responsiveness	Features
Aspirin	Aspirin binds to enzyme cyclo-oxygenase preventing conversion of arachidonic acid to thromboxane	Effect of aspirin lasts until a significant pool of new platelets is synthesized	Reduced aspirin responsiveness can be measured by impedance platelet aggregometry	Aspirin alone has little or no effect on angiographic or clinical restenosis
Clopidogrel	Irreversibly inhibits the ADP P2Y12 receptor	At steady state, the average inhibition level observed with a dose of 75 mg of clopidogrel per day is between 40%-60%	The prevalence of reduced clopidogrel response in patients is evaluated between 5% and 44% and is termed as HTPR	Some of the causes of clopidogrel HTPR include genetic polymorphisms of the P2Y12 receptor and of CYP3As, accrued release of adenosine phosphate, and up-regulation of other platelet activation pathways
Ticagrelor	Direct-acting, oral, newer reversible P2Y12 receptor antagonist	It binds allosterically to the platelet ADP P2Y12 receptor, thus, the binding does not cause a conformational change in the P2Y12 receptor. It has a short offset time	More predictable and potent than clopidogrel	Should be avoided in patients with moderate-to-severe hepatic impairment and high bleeding risk. Complications include lung injury and dyspnea due to endogenous adenosine release
Prasugrel	Oral irreversible inhibitor of the P2Y12 receptor	Effect of prasugrel lasts until a significant pool of new platelets is synthesized	Better inhibition for those with high HTPR	A 5%-6% or low percentage of non-responders
Cangrelor	Intravenous directly reversible P2Y12 inhibitor	Half-life 3-6 min	Rapid platelet aggregation with almost full recovery of platelet activity within 60-90 min of withdrawal	Useful to preload with antiplatelet therapy before the angiography should the patient's anatomy require urgent surgery

HTPR: High on treatment platelet reactivity.