Greater Collagen-Induced Platelet Aggregation Following Cyclooxygenase 1 Inhibition Predicts Incident Acute Coronary Syndromes

Platelets have several pathways that initiate aggregation such as thrombin-, collagen-, thromboxane-, and ADP-mediated pathways. Individuals vary widely in their ability to have platelet aggregation through each of these pathways. Furthermore, this variability is not correlated. In other words, an individual may have low aggregation though one pathway but may have high aggregation through another pathway. This phenomenon may be more important when we try to measure platelet aggregation the laboratory to assess whether there is increased risk of in vivo platelet aggregation (and hence cardiovascular events).

Collagen is one of the first agonists that initiates platelet aggregation at the site of vessel wall injury. Therefore, examining an association of collagen-mediated platelet aggregation with subsequent cardiovascular events makes sense. Moreover, if we can decrease variability in platelet aggregation by blocking one or another pathway, we may be better able to assess activation through collagen pathway.

Aspirin is commonly used for prevention of cardiovascular disease and works by inhibiting thromboxane-pathway an dis very effective in completely inhibiting activity through this pathway. Thus aspirin can be used to inhibit variability through one pathway and effect of collagen can be studied with fewer interactions. We followed the same logic in this paper where we examined platelet aggregation after 2-week aspirin therapy in healthy individuals. Most of these individuals did not use aspirin after the 2-week study period. During follow-up increased collagen-mediated platelet aggregation was significantly associated with acute coronary syndrome.

“After COX1 pathway inhibition, collagen-induced aggregation was significantly greater in participants with ACS compared with those without (29.0 vs. 23.6 ohms, p < 0.001). In Cox proportional hazards models, this association remained significant after adjusting for traditional cardiovascular risk factors (HR = 1.10, 95%CI = 1.06-1.15; p < 0.001).”