© 2015 International Society on Thrombosis and Haemostasis. 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.
|Journal||Journal of Thrombosis and Haemostasis|
|Publication status||Published - 1 Oct 2015|
- Blood platelets
- Cell-derived microparticles