Platelet response in practice: Applying new insights and tools for testing and treatment
POINT-OF-CARE PLATELET FUNCTION TESTING: CURRENT LIMITS, FUTURE ROLES
Dr. Bhatt: While we’re discussing platelet function testing, I found it interesting, Dr. Kottke-Marchant, that you said the use of bleeding time as a platelet test is finally going away. Testing of bleeding time has been around forever, but I agree that it doesn’t have much value in clinical practice. Do you think bleeding time will continue to have any role in drug development? Most phase 2 trials, and certainly phase 1 trials, still capture bleeding time to assess whether or not a drug is working. Should that, too, be jettisoned, or does bleeding time still have some merit in this context?
Dr. Kottke-Marchant: I would jettison it in drug development as well because of the considerable variability in bleeding time. It is not a test that can be standardized, and no quality control can be done. The results depend on skin turgor, age, and many other variables.
We need a global assay that will pick up multiple aspects of platelet function, such as flow-based adhesion, aggregation, and granule release. The bleeding time is a shear-dependent test, whereas the platelet aggregation test that is used in most drug trials is an artificial assay that measures only aggregation, but not under shear. The VerifyNow rapid platelet function analyzer does not measure platelets under shear and is not a global assay.
Dr. Marc Sabatine: I would underscore the need for a reliable point-of-care test of platelet function. When we prescribe a statin or an antihypertensive drug, we don’t just send the patient out the door and hope that everything will be okay. We measure the response, knowing that genotype, environmental factors, or medication factors can affect the response. When we prescribe an antiplatelet drug, we need a reliable point-of-care device to make certain that the patient is getting appropriate platelet inhibition.
I am reminded of a recent study of point-of-care measurement of platelet inhibition in patients receiving clopidogrel prior to nonemergent percutaneous coronary intervention (PCI).2 Rather than just treating patients with PCI and sending them out the door, the investigators kept giving patients clopidogrel and measuring their platelet inhibition until they achieved an appropriate degree of inhibition, after which PCI was performed. Event rates were significantly reduced in the patient group treated this way, which suggests a need to individualize therapy and move away from the “one size fits all” mindset.
Dr. Bhatt: Dr. Peacock, you’ve led a study of point-of-care assays in the emergency department. What might ultimately be the role of point-of-care testing in emergency medicine, and might it influence drug selection?
Dr. Peacock: My short answer is that I think there will be a role for point-of-care testing, with all the caveats that have been discussed. There may even be a day when we do genetic testing and look for DNA. Honestly, though, I’m somewhat of a skeptic because I’m not looking at the genetics. I see many patients who do crack cocaine who come to the emergency room with chest pain and have risk factors, but I send these patients home because they are not having an event. The real question is, “Is it an event?” If a patient is having an event and he or she has platelet resistance or hyperreactivity—whatever we term it—then you have to decide the next step.
As you mentioned, we just completed a study that evaluated a couple hundred patients for platelet inhibition resistance to aspirin, and one finding was that the incidence of platelet resistance to aspirin was much lower than we had anticipated. Studies from the literature suggest that the prevalence of resistance is around 30%, but in our study it was 6.5%.3
Dr. Kottke-Marchant: It depends on how and in whom you measure resistance. Different tests will give you different numbers. Even among studies using the same measurement techniques, the results depend on the patient population. If it’s a fairly stable cardiac population, you may see aspirin resistance rates of 4% or 5%. If it’s a population of patients who have had multiple MIs, the rate may be higher.
Dr. Peacock: That’s exactly my point. In the emergency department we see a mixed bag. We see many people who have had no prior events and have no acute event occurring. So in that setting you are going to get results that suggest that no intervention is required, whereas in that small percentage of patients in whom something is happening, your drug choice may be different.
Dr. Alexander: We are still talking about resistance to antiplatelet drugs as though it were a patient-level variable, but it’s my impression that it changes over time and within a patient.
Dr. Kottke-Marchant: It can change over time. There aren’t many good longitudinal studies. Most of the studies of “aspirin resistance” are really snapshot studies with measurements taken at one point in time. A term I prefer is “platelet reactivity.” To really assess treatment efficacy, we are going to have to look at the basal level of platelet reactivity.
