Author + information
- Bruce A. Kottke, MD⁎ ()
- ↵⁎Internal Medicine, Clark and Daughtrey LLP, 130 Pablo Street, Lakeland, Florida 33803
In their State-of-the-Art paper, Gasparyan et al. (1) provide an excellent review of the potential factors responsible for aspirin resistance. As they point out, a major problem is the lack of an accurate, reproducible, and practical quantitative test for measuring platelet activation. All commercially available tests use the measurement of the transmission of light through a suspension of platelets or the passage of cells through a narrow aperture. Both of these techniques are limited in that they detect macroaggregates but not microaggregates of platelets. This limitation is easily demonstrated by performing a dose-response test by adding linearly increasing doses of a glycoprotein IIb/IIIa inhibitor such as abciximab, eptifibatide, or tirofiban to the sample before measuring the percent inhibition produced by the addition. When this is done with any of the commercially available tests and the dose is plotted against the percent inhibition, the response in not linear, but flattens out at approximately 80% inhibition, which is close to the degree of inhibition that is likely to be clinically desirable. This problem can be overcome if, instead of using the commercial tests, one uses an automatic cell counter to count individual platelets before and after the addition of the agonist. The percent inhibition is the difference between the before and after counts divided by the before count. When a dose-response test with a glycoprotein IIb/IIIa inhibitor is performed by using this technique, the response is linear throughout the entire range of inhibition. An ideal test for platelet activation would eliminate the need for the use of an agonist. Such a test would reflect in vivo activation at the time the sample was drawn. To avoid use of an agonist, it would need to be extremely sensitive. To allow for establishment of its specificity, it would need to be quantitative. When platelets become activated, one of the first effects is the release of platelet microparticles that can be identified by flow cytometry. These microparticles have all of the surface markers of platelets that can be detected with fluorescent-labeled antibodies. Because each activated platelet releases large numbers of microparticles, each with multiple markers, a modified flow cytometer could be developed specifically to detect these markers on microparticles and, thus, be a very sensitive measure of platelet activation. Such a machine would have great utility as a tool for adjusting the doses of antiplatelet therapy, detecting resistance to antiplatelet agents such as aspirin and clopidogrel, and in detecting early acute cardiac events.
- American College of Cardiology Foundation