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Updated: Mar 14, 2026
Dynamic Multiparameter Platelet Function Assessment Using a Capacitive Biosensor
Published on: May 2, 2025
Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment
Isabella Massimi, Lavinia Vittoria Lotti, Flavia Temperilli
1Fabio M. Pulcinelli, MD, Department of Experimental Medicine, "Sapienza" University of Rome, Viale Regina Elena 324, 00161, Rome, Italy, Tel.: +39 06 49973002, Fax: +39 06 4452955,
Abstract:
Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1-independent mechanism.
Insights
Chronic aspirin treatment increases platelet multidrug resistance protein 4 (MRP4). This MRP4 overexpression in patients leads to reduced aspirin effectiveness and increased residual platelet reactivity, impacting thrombus formation.
Area of Science:
- Pharmacology
- Hematology
- Biochemistry
Background:
- Platelet multidrug resistance protein 4 (MRP4) overexpression can reduce aspirin's efficacy.
- Aspirin treatment in vivo enhances platelet MRP4 expression, potentially inhibiting platelet function.
Purpose of the Study:
- To investigate if MRP4 expression is elevated in platelets of patients on chronic aspirin therapy.
- To determine the correlation between MRP4 expression and residual platelet reactivity in these patients.
Main Methods:
- Evaluated mRNA and protein levels of MRP4 in four groups: healthy volunteers, aspirin-free controls, recent aspirin users (<1 month), and chronic aspirin users (>2 months).
- Assessed platelet aggregation and serum Thromboxane B2 (TxB2) levels.
- Compared platelet aggregation in vitro with and without aspirin based on MRP4 levels.
Main Results:
- Chronic aspirin users (ASA>2 months) showed significantly higher MRP4 mRNA and protein expression compared to other groups.
- Patients with high platelet MRP4 levels exhibited increased serum TxB2 and collagen-induced platelet aggregation.
- In vitro aspirin treatment showed higher collagen-induced aggregation in platelets with high MRP4 levels.
Conclusions:
- Platelets from patients under chronic aspirin treatment with high MRP4 levels display increased residual platelet reactivity.
- This increased reactivity is attributed to both incomplete cyclooxygenase-1 (COX-1) inhibition and COX-1-independent mechanisms.
- MRP4 appears to be a key factor in aspirin resistance in chronic aspirin users.
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