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Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
The influencing factors for clopidogrel-mediated platelet inhibition are assay-dependent
Thomas Gremmel1, Sabine Steiner, Daniela Seidinger
1Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. thomas.gremmel@meduniwien.ac.at
Insights
Clopidogrel response varies based on the platelet function test used. Factors influencing clopidogrel
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Previous studies on clopidogrel response have used limited test systems, yielding inconsistent results.
- The identification of factors influencing clopidogrel's antiplatelet effect may differ across various platelet function assays.
- Understanding assay-dependent variability is crucial for accurate clopidogrel therapy monitoring.
Purpose of the Study:
- To investigate whether factors influencing clopidogrel-mediated platelet inhibition are dependent on the specific assay used.
- To compare the impact of various clinical and laboratory variables on platelet reactivity across multiple platelet function tests.
Main Methods:
- Adenosine diphosphate (ADP)-inducible platelet reactivity was assessed in 288 patients post-angioplasty using five assays: LTA, VerifyNow P2Y12, VASP, MEA, and Impact-R.
- Univariate and multivariate regression analyses evaluated the influence of patient demographics, comorbidities, and concomitant medications on clopidogrel response.
- Key variables included age, BMI, diabetes, smoking, hypertension, hyperlipidemia, C-reactive protein, platelet count, creatinine, and use of CCBs, statins, PPIs, beta-blockers, ACE inhibitors, and ARBs.
Main Results:
- No single influencing variable was consistently associated with clopidogrel response across all tested assays.
- Age ≥ 75 and calcium-channel blocker (CCB) use were linked to higher platelet reactivity by LTA and VerifyNow P2Y12.
- Body mass index (BMI) showed a linear association with platelet reactivity in VASP and MEA assays, while platelet count had conflicting associations in MEA and Impact-R.
Conclusions:
- The factors influencing platelet reactivity during clopidogrel therapy are significantly assay-dependent.
- This assay variability highlights the need for careful interpretation of platelet function test results in clinical practice.
- Future research should consider assay-specific factors when evaluating clopidogrel response and its clinical implications.
Background:
Influencing factors for clopidogrel-mediated platelet inhibition have only been evaluated by one or two different test systems in the same population so far. Since previous studies revealed poor correlations between the various platelet function tests, the identification of influencing variables for clopidogrel response may vary from one test system to the next. We therefore investigated whether the influencing factors for clopidogrel-mediated platelet inhibition depend on the used assay.
Patients And Methods:
Adenosine diphosphate (ADP)-inducible platelet reactivity was assessed by light transmission aggregometry (LTA), the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry (MEA), and the Impact-R in 288 patients after angioplasty and stenting for cardiovascular disease. By univariate and multivariate regression analyses, we evaluated the impact of age ≥ 75, gender, body mass index (BMI), diabetes, active smoking, hypertension, hyperlipidemia, C-reactive protein, platelet count, creatinine, use of calcium-channel blockers (CCBs), statins, proton pump inhibitors, beta blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers on clopidogrel-mediated platelet inhibition in each test system.
Results:
None of the independent influencing variables was consistent through all test systems. Only by LTA and the VerifyNow P2Y12 assay, age ≥ 75 and the use of CCBs were independently associated with higher on-treatment platelet reactivity. Only by the VASP assay and MEA, on-treatment platelet reactivity increased linearly with BMI. Further, only by MEA, residual ADP-inducible platelet reactivity increased linearly with platelet count, whereas an increase in platelet count was independently associated with a decrease in ADP-inducible platelet activation by the Impact-R.
Conclusion:
The influencing factors for platelet reactivity during clopidogrel therapy are assay-dependent.
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