From the Guidelines
The correct answer is (a) aspirin, as it is not the best choice, but clopidogrel, which is not an option, is the most effective inhibitor of adenosine diphosphate–induced platelet aggregation, as shown in the study by 1. However, among the given options, aspirin is not the most effective, but another antiplatelet agent, such as clopidogrel, has been shown to be effective in blocking adenosine diphosphate–stimulated platelet aggregation, as stated in the study by 1. Some key points to consider:
- Aspirin inhibits the enzyme cyclooxygenase 1 (COX-1) and therefore thromboxane A2 synthesis, whereas clopidogrel inhibits one of the platelet receptors of adenosine diphosphate (ADP), the P2Y12 receptor, as mentioned in the study by 1.
- Thromboxane A2 and ADP are platelet activators with specific receptors, and they essentially come from platelets activated by sub-endothelial collagen exposed after a vascular injury and the first traces of thrombin, as explained in the study by 1.
- Clopidogrel is an oral thienopyridine prodrug that irreversibly inhibits the adenosine diphosphate receptor on the platelet, resulting in a reduction in platelet aggregation through a different mechanism than aspirin, as stated in the study by 1.
- The use of clopidogrel in ACS patients with a high likelihood of needing CABG requires weighing the risk of bleeding if given against the potential for perioperative ACS events if withheld, as mentioned in the study by 1. Some other options to consider:
- Dipyridamole inhibits adenosine diphosphate (ADP)-induced platelet aggregation by preventing the uptake of adenosine into platelets, red blood cells, and endothelial cells, but it is not among the options provided.
- Heparin acts on the coagulation cascade rather than directly on platelets, while Coumadin (warfarin) inhibits vitamin K-dependent clotting factors, as explained in the example answer.
- The study by 1 provides more recent and relevant information on the topic, and it should be considered as the primary source for this answer.
From the FDA Drug Label
Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells and erythrocytes in vitro and in vivo; the inhibition occurs in a dose-dependent manner at therapeutic concentrations (0.5-1. 9 mg/mL). This inhibition results in an increase in local concentrations of adenosine which acts on the platelet A2-receptor thereby stimulating platelet adenylate cyclase and increasing platelet cyclic-3',5'-adenosine monophosphate (cAMP) levels Via this mechanism, platelet aggregation is inhibited in response to various stimuli such as platelet activating factor (PAF), collagen and adenosine diphosphate (ADP). The correct answer is (c) dipyridamole, as it inhibits platelet aggregation in response to adenosine diphosphate (ADP) by increasing platelet cyclic-3',5'-adenosine monophosphate (cAMP) levels 2.
From the Research
Inhibition of Adenosine Diphosphate-Induced Platelet Aggregation
- The correct answer is (c) dipyridamole, as it has been shown to inhibit platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma 3, 4.
- Dipyridamole's slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets, leading to an anti-aggregatory effect 3.
- Aspirin (a) does not affect the potentiating effects of heparin on platelet aggregation 5, and its effect on platelet-derived growth factor A chain mRNA levels in human saphenous vein endothelial cells and smooth muscle cells is not significant 6.
- Heparin (b) actually potentiates platelet aggregation induced by some agonists, including ADP 5.
- Coumadin (d) is not mentioned in the provided studies as having an effect on adenosine diphosphate-induced platelet aggregation.
- The P2Y12 receptor plays a major role in amplifying platelet aggregation, and its overexpression is associated with enhanced ADP-induced aggregation in platelets from patients with thrombotic primary antiphospholipid syndrome (t-PAPS) 7.