Thanks to our 57 FF participants for your responses to our February 2022 Quick Question.
The question stem was: “What single agonist is your first choice to measure platelet response to aspirin?”
- ADP: 14% 
- TRAP: 2% 
- Collagen: 2% 
- Epinephrine: 28% 
- Arachidonic acid: 54% 
Although this question is a poll, my choice is arachidonic acid [#5], which directly activates the platelet eicosanoid synthesis pathway. This pathway is inactivated by aspirin as aspirin irreversibly acetylates the essential enzyme cyclooxygenase, and arachidonic acid is the most directly related.
ADP-triggered aggregation may also detect the aspirin response, as it activates the eicosanoid synthesis pathway subsequent to binding P2Y12 platelet membrane receptors. Although ADP detects the aspirin effect, its initial concentration must be carefully managed to generate the desired platelet response. Likewise, collagen may be employed, although it also acts through a platelet membrane receptor, glycoprotein Ia/IIa, or glycoprotein VI. Both ADP and collagen-induced aggregation may be affected by receptor variances as well as aspirin.
Epinephrine activates platelets through the alpha-2 adrenergic receptor which then acts through the same pathways as ADP, closely duplicating ADP-induced aggregometry responses. Epinephrine is not used in whole blood lumiaggregometry, as its response is unpredictable.
Thrombin-receptor activating peptide [TRAP] may bypass the eicosanoid synthesis pathway altogether and generate aggregation in the presence of aspirin. TRAP is most useful in detecting reduced platelet secretion.
There are many and varied approaches to platelet aggregometry, and as always, your comments are invited.
I agree with your explanations. However, most labs do not have the resources to run the whole blood platelet aggregation assay. Most labs employ the PFA-100 analyzer and Verify Now as you know to get the answer. In PFA-100, the choice of assays for normal platelet function which is performed on whole blood are 1st: epinephrine/collagen, and if that is abnormal then 2nd: ADP/collagen.
Hence, my choice was ‘epinephrine’ as the question did not specify whole blood platelet aggregometry.