Laboratory measurement of platelet reactivity

More than 50 million Americans take a daily aspirin in an effort to reduce the risk of heart attacks. Plavix® (clopidogrel) is the second-biggest selling prescription drug worldwide, with almost 30 million prescriptions filled annually.1 This drug is taken to reduce platelet reactivity, which can lead to heart attack, stroke, and death. Yet it has been well established that there is a high degree of individual variability in response to clopidogrel and similar drugs, with approximately one in three patients not responding adequately.2 Patients who do not respond adequately may be at significantly greater risk for major adverse cardiac events.3-7 The introduction of newer antiplatelet drugs as well as cheaper, generic versions of clopidogrel, following Plavix’s loss of patent protection on May 17, 2012, changes the economic incentives associated with managing these risks. In this scenario, laboratory medicine can play a critical role in clinical decision making.

Transformation of healthcare

Healthcare is transforming, especially as the new science of personalized medicine takes some of the emphasis from more traditional diagnostics to more accurate tailored disease diagnostics and management, which allows healthcare providers to be more efficient. Today, rapid testing provides fast, actionable information that reduces the time to diagnosis, treatment, and cure.

For individuals taking antiplatelet medications, platelet reactivity testing measures individual patients’ levels of platelet reactivity. There is a high degree of bio-variability in response due to multiple genetic factors (e.g., CYP2C19 polymorphisms), cellular factors (e.g., variant expression of enzymes), and clinical factors (e.g., diabetes). Platelet reactivity testing provides clinicians with real-time laboratory data, and can be provided on demand, during any shift, any day, as well as around the clock if needed, thereby allowing rapid interventions by clinicians in many different hospital settings. Such interventions can reduce morbidity and mortality and improve patient safety, in addition to improving quality and cost outcomes.

Improving both cost and quality

With the advent of lower-cost generic clopidogrel, there may be co-pay reductions for patients and drug cost reductions for healthcare systems. However, with the variability in response to clopidogrel, saving money on a generic drug may not reduce total healthcare costs if it leads to more patients returning to the hospital due to heart attacks, stroke, etc. Patients who do not respond adequately to their antiplatelet medications have a higher 30-day readmission rate than patients who are responding adequately.8 Physicians who work in hospitals were surveyed recently regarding how the availability of generic clopidogrel might influence their use of platelet reactivity testing. The majority indicated that concerns about variability in response would make them more interested in this type of laboratory test.9

Platelet reactivity testing in the lab

To assess the effect of antiplatelet ther-apy, the standard has become light transmission and whole blood aggregation, technologies which have been incorporated into a newer generation of point-of-care platelet function analyzers. In these instruments, ADP is contained in the reagents in order to initiate activity of the platelet P2Y12 receptor. Substances known to specifically block the platelet’s P2Y12 receptor include the thienopyridine class of drugs, including clopidogrel, prasugrel, ticagrelor, and ticlopidine. Aggregation results report the amount of ADP receptor- mediated aggregation specific to these platelet receptors, and the degree of platelet receptor blockade is reported by a change in light transmittance as the platelets bind fibrinogen and aggregate.

“Despite the clear benefits of clopidogrel therapy, a considerable number of cardiovascular events continue to occur” states Dr. Ellinor Peerschke, Vice Chair, Laboratory Medicine and Head of Hematology and Coagulation Laboratories at Memorial Sloan Kettering Cancer Center, New York. “This is reported to be due, at least in part, to individual response variability, which is a multifactorial process, including multiple genetic factors, cellular factors and clinical factors. Platelet function is controlled by both genes and environment. The incorporation of both platelet function and genetic testing is necessary to personalize P2Y12 antiplatelet therapy. The effective evaluation of platelet function for patients receiving antiplatelet therapy requires a rapid turnaround time, low complexity, 24/7 availability, and results associated with defined patient outcomes. The new generation of point-of-care whole blood platelet function analyzers meets these requirements and provides results that most closely resemble platelet aggregation.”

Platelet reactivity testing in clinical practice

Richard Shlofmitz, MD, Chairman, Department of Cardiology at St. Francis Hospital in Roslyn, New York, uses platelet reactivity testing in his interventional cardiology practice, for patients who have had a PCI (percutaneous coronary intervention—i.e., a stent procedure). “I am a true believer that the ‘one size fits all’ approach to treating patients on antiplatelet therapies is sub-optimal. This has led me to ordering platelet reactivity tests on many of my patients after a PCI.  I can rapidly receive a PRU result from the platelet reactivity test we utilize and can make informed therapy decisions based on what I know to be important factors affecting my individual patients. For a patient with a drug-eluting stent, it is critical to have sufficient platelet inhibition. If you don’t assess patients’ platelet reactivity to see how they are responding to their antiplatelet medications, you cannot be sure that you have platelet inhibition. In my practice, anywhere from 30% to 50% of people taking Plavix are not actually inhibited with a routine dose.” 

Quality improvement and value assessment

Many facilities are integrating laboratory medicine into quality improvement initiatives. These initiatives often yield positive economic outcomes in addition to improved quality metrics. Models are created to support these types of initiatives. One such model, a Quality Improvement and Value Assessment Tool, incorporates platelet reactivity testing to estimate and model the potential impact of integrating platelet reactivity testing into cardiovascular patient care.10 This model examines two clinical scenarios: 1) the potential reduction in 30-day hospital readmissions following stent procedures, resulting from the measurement of platelet reactivity and modification of antiplatelet therapy to achieve a target level; and 2) the potential reduction in pre-op medical admission days for CABG patients, resulting from measurement of platelet reactivity and determination of when CABG patients would no longer be displaying an antiplatelet effect following discontinuation of a P2Y12 inhibitor.

For a typical American hospital with 650 PCI patients per year and 225 CABG patients per year, the Quality Improvement and Value Assessment Tool estimates that integrating platelet reactivity testing into patient care protocols could yield 3.3 fewer 30-day readmissions, 80 fewer pre-CABG medical admission days, and cost avoidance of over $120,000 per year, for a 3-year total of $365,000. In comparison, the associated cost of the instrument and reagents for the system used in this model is estimated at $30,000 the first year, and $63,000 over 3 years. The platelet reactivity testing costs used in this scenario were specific to a point-of-care platelet aggregation instrument.

Laboratories can play a critical role in the transformation of healthcare to a more personalized approach, yielding better quality and cost outcomes for the entire healthcare system. The offering of platelet reactivity testing is a compelling example of laboratory leadership driving improvements that benefit patients, physicians and healthcare administration.


  1. IMS Institute for Healthcare Informatics, April 2011.
  2. Dupont AG, Gabriel DA, Cohen MG. Antiplatelet therapies and the role of antiplatelet resistance in acute coronary syndrome. Thromb Res. 2009;124(1):6-13.
  3. Patti G, Nusca A, Mangiacapra F, et al. Point-of-care measurement of clopidogrel
    responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2008;52:1128-1133.
  4. Marcucci R, Gori AM, Paniccia R, et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay. Circulation. 2009;119(2):237-242.
  5. Cuissett T, Hamilos M, Sarma J, et al. Relation of low response to clopidogrelassessed with point-of-care assay to periprocedural myonecrosis in patients undergoingelective coronary stenting for stable angina pectoris. Am J Cardiol. 2008;101(12):1700-1703.
  6. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008;29(8):992-1000.
  7. Brar SS, ten Berg J, Marcucci R, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. J Am Coll Cardiol. 2011;58(19):1945-1954.
  8. Wiviott SD, Braunwald E, McCabe CH, et al for the Triton-TIMI 38 investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001-2015.
  9. Sermo survey conducted by Accumetrics, Inc., 2012. Results on file.
  10. Mackowiak J, Schmidt D, Bartolomeo B, Coleman J. An economic model incorporating a point of care platelet function assay: a quality improvement and value assessment tool. Abstract accepted for AACC National Meeting, July 2012.

Denise Uettwiller-Geiger, PhD, DLM (ASCP) is Director of Laboratory Services & Clinical Trials at John T. Mather Memorial Hospital in Port Jefferson, NY. John Mackowiak, PhD, is President of the Center for Outcomes Research, Nashville, TN.