Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases

Antonova O.A.1 , Golubeva N.V.1, Yakushkin V.V.1, Zyuryaev I.T.1, Krivosheeva E.N.1, Komarov A.L.1, Martynyuk T.V.1, Mazurov A.V.1

1. National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow, Russia
Section: Clinical and Diagnostic Research
DOI: 10.18097/PBMC20226804288      PubMed Id: 36005847
Year: 2022  Volume: 68  Issue: 4  Pages: 288-296
Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylserine (PS), a substrate for the assembly of coagulation complexes, and some of them tissue factor (TF), the primary initiator of coagulation cascade reactions. We compared the coagulation activity and amount of MP in the blood of healthy donors (n=34) and patients with myocardial infarction (MI) (n=32), advanced atherosclerosis (AA) (n=32) and idiopathic pulmonary arterial hypertension (IPAH) (n=19). Total MP fraction was obtained from blood plasma by sedimentation at 20000 g, 30 min. The coagulation activity of PM isolated from 100 μl of donor and patient plasma was determined using a modified recalcification test. MP were added to substrate plasma devoid of endogenous MF, plasma was recalcified, and clotting was recorded by changes in optical density (A450), determining lag phase (min) and maximum rate (Vmax, %A450/min). MP were counted by flow cytometry as PS+ particles (lactadgerin-FITC staining) smaller than 1 μm and their concentration was expressed as 105 MP/μl plasma. MP in all patient groups accelerated plasma clotting more effectively than donor MP. Lag phase compared with donors (11.8 [11.0-13.1] median and interquartile range) was shorter in patients with AA (8.8 [7.0-10.3], p<0.001), MI (9.5 [7.3-12.1], p=0.004), ILAH (9.8 [6.0-12/0], p=0.015), and Vmax compared with donors (13.1 [11.7-13.9]) was higher in patients with AA (20.8 [15.2-25.3], p<0.001), ILAH (17.8 [14.9-22.5], p=0.001), but not MI (12.6 [11.1-15.7], p=0.941). MP concentrations compared with donors (0.59 [0.34-0.78]) were higher in patients with AA (0.74 [0.50-1.18], p=0.004), lower in patients with MI (0.29 [0.23-0.55], p<0.001), and not significantly different in patients with ILAH (0.43 [0.30-0.76], p=0.445). In all groups of patient, there was a significant correlation between MP concentration of and parameters 1/lag phase and Vmax of plasma clotting. The data obtained show that the increase in total coagulation activity of MP can be explained by an increase in their concentration only in patients with AA. Anti-TF antibodies did not alter clotting parameters in the presence of MP from donors and patients, indicating that TF is not involved in the realization of the coagulation properties of the tested MP. At the same time, in all groups of patients there was a significant increase in the expression of PS on the surface of MP compared to donors, which could be one of the reasons for their increased coagulation activity.
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Keywords: membrane microparticles, blood coagulation, myocardial infarction, atherosclerosis, pulmonary hypertension

Antonova, O. A., Golubeva, N. V., Yakushkin, V. V., Zyuryaev, I. T., Krivosheeva, E. N., Komarov, A. L., Martynyuk, T. V., Mazurov, A. V. (2022). Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases. Biomeditsinskaya Khimiya, 68(4), 288-296.
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