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Updated: Jun 19, 2026
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Effects of clopidogrel on "aspirin specific" pathways of platelet inhibition
Alex R Hobson1, Zeshan Qureshi, Phil Banks
1Wessex Cardiothoracic Unit, Southampton University Hospital, UK. alex.hobson@suht.swest.nhs.uk
Insights
Current methods assessing clopidogrel response miss its effects on arachidonic acid (AA) pathways. This study reveals clopidogrel potentiates aspirin
Area of Science:
- Pharmacology and Toxicology
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Standard assessment of clopidogrel response relies on adenosine diphosphate (ADP)-induced platelet aggregation.
- This method overestimates poor responders and may not capture all of clopidogrel's antiplatelet effects.
- Arachidonic acid (AA)-induced platelet activation represents an aspirin-specific pathway potentially influenced by clopidogrel.
Purpose of the Study:
- To investigate clopidogrel's effect on AA-induced platelet activation using a novel near-patient assay.
- To determine if clopidogrel has effects on AA pathways that are not detected by standard ADP-induced assays.
- To explore potential synergistic effects between clopidogrel and aspirin on platelet activation.
Main Methods:
- A novel near-patient assay measuring Thrombelastogram PlateletMapping was employed.
- Blood samples were collected from 34 healthy volunteers and 36 patients on daily aspirin therapy.
- Measurements of platelet aggregation (AUC15, %PIn, %CIn) were taken before and 6 hours after a 600 mg clopidogrel loading dose, using both ADP and AA stimulation.
Main Results:
- Clopidogrel significantly reduced AA-induced platelet activation in both volunteers (27.2% reduction in AUC15) and patients (35.0% reduction in AUC15).
- Significant increases in percentage platelet inhibition (%PIn) and percentage clotting inhibition (%CIn) via the AA pathway were observed in both groups post-clopidogrel.
- These AA-specific effects were independent of ADP-induced changes and suggest a potentiation of aspirin's antiplatelet activity.
Conclusions:
- Clopidogrel exhibits effects on AA-induced platelet activation that are not detected by standard ADP-based assays.
- Clopidogrel demonstrates aspirin-synergistic effects, potentially enhancing aspirin's antiplatelet efficacy.
- The findings suggest a clinically relevant antiplatelet effect of clopidogrel via the AA pathway, necessitating a re-evaluation of current response assessment methods.
Abstract:
The most widely accepted methods of assessing response to clopidogrel involve isolated ADP-induced platelet aggregation. Whilst poor response determined by these assays correlates with adverse clinical events, the number of "poor responders" is far higher than the number of events attributed to treatment failure. Clopidogrel may have effects that cannot be assessed using isolated ADP-induced aggregation. We have investigated the effect of clopidogrel on Arachidonic Acid (AA) induced platelet activation-an "aspirin specific" pathway using a novel near patient assay. Thirty four volunteers on no medication and 36 patients, on maintenance therapy with aspirin 75 mg daily, were recruited. Blood tests for Thrombelastogram PlateletMapping were taken immediately prior to and 6 hours after administration of a 600 mg clopidogrel loading dose. Changes in the area under the response curve at 15 minutes (AUC15) with both ADP- and AA-stimulation were calculated as were the corresponding percentage platelet and percentage clotting inhibition (%PIn and %CIn). There were predictable and significant changes in the AUC15 of the ADP channel in response to clopidogrel and the corresponding %PIn and %CIn in both volunteers and patients. There were also significant reductions in the AUC15 of the AA channel (presented as Mean +/- 95%CI), by 27.2 +/- 11.8%, p = 0.005 in volunteers and 35.0 +/- 8.2%, p < 0.001 in patients) and increases in the %PIn and %CIn calculated using the AA channel in volunteers (by 20.0 +/- 11.4%, p + 0.02 and 32.3 +/- 12.8%, p < 0.001 respectively) and patients (by 24.2 +/- 8.6%, p < 0.001 and by 18.0 +/- 8.6, p < 0.001 respectively). Clopidogrel has both independent and aspirin-synergistic effects on AA-induced platelet activation suggesting potentiation of the antiplatelet activity of aspirin. This effect may be clinically important and is not detected by current "gold standard" methods of assessing response to clopidogrel.
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