Circulating Microvesicles in Convalescent Ischemic Stroke Patients: A Contributor to High-On-Treatment Residual Platelet Reactivity?

Diana Schrick; Tihamér Molnár; Margit Tőkés-Füzesi; Abigél Molnár; Erzsébet Ezer

doi:10.31083/j.fbl2705158

Circulating Microvesicles in Convalescent Ischemic Stroke Patients: A Contributor to High-On-Treatment Residual Platelet Reactivity?

Front Biosci (Landmark Ed). 2022 May 16;27(5):158. doi: 10.31083/j.fbl2705158.

Authors

Diana Schrick¹, Tihamér Molnár¹, Margit Tőkés-Füzesi^{2

3}, Abigél Molnár⁴, Erzsébet Ezer¹

Affiliations

¹ Department of Anaesthesiology and Intensive Care, University of Pécs, Medical School, Clinical Centre, 7624 Pécs, Hungary.
² Department of Laboratory Medicine, University of Pecs, Medical School, Clinical Centre, 7624 Pécs, Hungary.
³ Central Laboratory, Szigetvar Hospital, 7900 Szigetvár, Hungary.
⁴ Department of Medical Biology and Central Electron Microscopic Laboratory, University of Pécs, Medical School, 7624 Pécs, Hungary.

PMID: 35638425
DOI: 10.31083/j.fbl2705158

Abstract

Introduction: Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next vascular event. Patients with high-on-treatment platelet reactivity (HTPR) had a significantly higher risk for ischemic stroke. Here, we aimed to explore associations among circulating microparticles and responsivness to antiplatelet (clopidogrel) therapy.

Methods: A total of 18 patients on clopidogrel therapy due to secondary stroke prevention were rospectively recruited into this study. Twenty age-matched healthy subjects served as controls. Flow cytometric measurements of microparicles (MVs) and data analysis were performed on Beckman-Coulter FC-500 cytometer with CXP software. Besides, platelet aggregometry data were revealed. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate.

Results: The total number of circulating MVs, and particularly the platelet derived CD42+ and PAC-1+ were significantly higher in post-stroke patients (p < 0.001). The platelet aggregation in the whole blood (area under the curve, AUC) showed a significant negative correlation with the total number of MPs in the lower blood sample after 1-hour gravity sedimentation (r = -0.650, p = 0.005). Next, we analyzed associations among MPs and aggregometry data obtained from clopidogrel responders and non-responders. Both, area under the curve (AUC) and velocity in the whole blood showed opposite correlation with the total number of MVs in the lower blood sample after 1-hour gravity sedimentation. Importantly, a significant negative correlation was observed for the velocity (r = -0.801, p = 0.005), but not for the AUC in responders. Platelet derived CD42+ and PAC-1+ MVs showed positive correlations with neutrophils in the lower blood sample (p = 0.008 and p = 0.006 respectively).

Conclusions: Circulating MVs may allow to monitor the response to antiplatelet therapy in post-stroke patients. In addition, the link between platelet derived MVs and neutrophil granulocytes might become therapeutic targets in the future.

Keywords: antiplatelet therapy; clopidogrel; ischemic stroke; microvesicles; neutrophil; platelet.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Platelets / physiology
Cell-Derived Microparticles*
Clopidogrel / therapeutic use
Humans
Ischemic Stroke*
Platelet Aggregation Inhibitors / therapeutic use
Stroke* / drug therapy

Substances

Platelet Aggregation Inhibitors
Clopidogrel