Growing thrombi release increased levels of CD235a+ microparticles and decreased levels of activated platelet‐derived microparticles. Validation in ST‐elevation myocardial infarction patients

• Published in: Journal of thrombosis and haemostasis Vol. 13; no. 10; pp. 1776 - 1786
• Main Authors: Suades, R., Padró, T., Vilahur, G., Martin‐Yuste, V., Sabaté, M., Sans‐Roselló, J., Sionis, A., Badimon, L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.10.2015
• Subjects: Aged; Biomarkers - blood; blood platelets; Blood Platelets - metabolism; Case-Control Studies; Cell-Derived Microparticles - metabolism; cell‐derived microparticles; Coronary Thrombosis - blood; Coronary Thrombosis - diagnosis; Coronary Thrombosis - therapy; erythrocytes; Female; Flow Cytometry; Glycophorin - metabolism; hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - diagnosis; Myocardial Infarction - therapy; Percutaneous Coronary Intervention; Phenotype; Platelet Activation; Predictive Value of Tests; Reproducibility of Results; Thrombectomy; Thrombin - metabolism; thrombosis; Time Factors; Treatment Outcome; blood platelets; erythrocytes; thrombosis; cell-derived microparticles; hemodynamics
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.13065

Summary Background Local fluid dynamics and exposed atherosclerotic lesions regulate thrombus formation. Activated cells in the attached thrombi release microparticles to the circulation (circulating microparticles [cMPs]); however, their phenotype is unknown. Objectives To investigate the specific phenotype of the cMPs released by growing thrombi. Methods/patients cMPs released by thrombi growing in different well‐characterized thrombogenic conditions were investigated. cMP contents just before and immediately after perfusion of the thrombogenic surfaces were analyzed by triple‐labeling flow cytometry. cMPs were tested for their thrombin‐generating capacity. The cMPs identified in the ex vivo perfusion experiments were validated in blood of ST‐elevation myocardial infarction (STEMI) patients undergoing thrombectomy and percutaneous coronary intervention. Culprit coronary blood (STEMI‐CCB) and peripheral artery blood (STEMI‐PAB) were simultaneously analyzed and compared with peripheral artery blood from age‐matched controls (C‐PAB) and peripheral artery blood from patients who had recovered from acute coronary syndrome (ACS) (pSTEMI‐PAB). Results The levels of annexin V+ cMPs significantly increased in blood collected after perfusion of the exposed thrombogenic surfaces. cMP release was directly related to the formed thrombus mass and the plasma procoagulant activity. Post‐thrombus blood showed higher thrombin generation potential and contained higher levels of cMPs carrying glycophorin‐A (CD235a+; erythrocyte‐derived microparticles [ErMPs]) than preperfusion blood (P < 0.05), whereas the levels of cMPs carrying activated and adhesion platelet markers were decreased. STEMI‐CCB and STEMI‐PAB had significantly higher ErMP levels than control blood (P < 0.005). ErMP levels were also significantly higher in STEMI‐PAB than in pSTEMI‐PAB, validating the experimental mechanistic studies and suggesting that ErMPs are markers of ongoing coronary thrombosis (C‐statistics: 0.950; 95% confidence interval 0.889–1.000; P < 0.001). Conclusion Glycophorin‐A‐rich microparticles are released from evolving growing thrombi into the distal perfusing blood, and can be measured in peripheral blood. CD235a+ cMPs may constitute a novel systemic biomarker of ongoing thrombosis.