Pharmacodynamics of Platelet Inhibition with Aspirin: Feasibility for Detection of Suboptimal Platelet Inhibition
Authors: Schaefer Jordan , Davis John , Schwartz Kenneth A. 
Published: October 2019

Abstract 4361

Introduction:

Patients with diabetes mellitus and or metabolic syndrome may or may not be maximally protected from future vascular events with aspirin. To be maximally protected at least 90% of platelets should be inhibited by aspirin (aspirinated). Since platelet acetylation by aspirin is limited to the first 30 minutes after ingestion, in conditions associated with increased platelet production the percentage of aspirinated platelets could be diluted to less than 90% with the usual daily dosing. We studied the pharmacodynamics of aspirin inhibition of platelets to evaluate the feasibility of developing a metric that would detect suboptimal aspirin inhibition of platelets.

Methods:

The slope of the platelet prostaglandin agonist (PPA) stimulated light aggregometry curve was used to gage the degree of platelet inhibition with aspirin.(Schwartz J. Lab Clin Med 2002; 139:227) Seven normal subjects were studied. After observed ingestion of 325mg of aspirin, the degree of platelet inhibition was studied at the following post aspirin time points; 0, 8hrs, 24hrs and 48hrs. Ex-vivo dilution curves were constructed using time 0 as 100% non-aspirinated and 1hr post aspirin as 100% aspirinated under the assumption that over 24hrs 10% of platelets are newly formed and non-aspirinated. Statistical evaluations were performed for each subject studied using both within subject comparisons and considering the group as a whole, between-subject comparisons.

Results:

Within group comparisons:

A linear regression analysis comparing the in-vivo PPA aggregometry slopes with the PPA slopes obtained via ex-vivo dilutions demonstrated that the ex-vivo dilution curves for a particular subject reliably predicted the degree of aspirin inhibition observed in-vivo for that subject at the following time points with their corresponding percentages of aspirinated platelets; 8hrs (97% aspirinated) 24hrs (90% aspirinated) and 48hrs (80% aspirinated) (r2=0.6, p< 0.001). In addition, a direct in group comparison showed no differences between the in-vivo PPA slopes and those obtained with ex-vivo dilutions with 8 hr. and 48 hr. time points (p=0.16 and p=0.31, respectively), but a difference was observed at the 24 hr. time point (p=0.02). Entire group comparisons: Platelet inhibition with aspirin was highly variable among subjects. When analyzed as a group, the ex-vivo dilution curves were not predictive of the slopes obtained in-vivo. The PPA slopes observed in-vivo were significantly different from those obtained from the ex-vivo dilution curves at all of the time points (p<0.05).

Conclusions:

1. In normal subjects the ex-vivo dilution curve for a particular subject reliably predicts the degree of platelet inhibition observed in-vivo for that subject. 2. The variation in aspirin inhibition among subjects is large and suggests that the development of a metric to detect suboptimal platelet inhibition with aspirin is only possible if the individual subjects serve as their own control.

Disclosures:

No relevant conflicts of interest to declare.