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[Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases]
O A Antonova1, N V Golubeva1, V V Yakushkin1
1National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow, Russia.
Abstract:
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.
Insights
Membrane microparticles (MPs) from patients with cardiovascular diseases significantly accelerate blood clotting compared to healthy donors. These MPs, carrying phosphatidylserine and tissue factor, indicate increased thrombotic risk in these conditions.
Area of Science:
- Hematology
- Cardiovascular Research
- Biochemistry
Background:
- Membrane microparticles (MPs) are cell-derived vesicles released during cell activation or damage.
- MPs possess procoagulant properties due to surface phosphatidylserine (PS) and tissue factor (TF).
- Elevated MP levels are associated with various pathological conditions.
Purpose of the Study:
- To compare the quantity and coagulation activity of MPs in healthy donors versus patients with myocardial infarction (MI), advanced atherosclerosis (AA), and idiopathic pulmonary arterial hypertension (IPAH).
- To investigate the role of MPs in accelerating blood clotting in these patient cohorts.
Main Methods:
- Isolation of total MP fraction from blood plasma via high-speed centrifugation (20000 g).
- Assessment of coagulation activity using a modified recalcification test, measuring lag phase and maximum clotting rate (Vmax).
- Quantification of MPs by flow cytometry using PS+ staining (lactadherin-FITC) and expressing concentration as 10^5 MPs/μl plasma.
Main Results:
- MPs from all patient groups (MI, AA, IPAH) demonstrated significantly accelerated plasma clotting compared to healthy donors.
- A shorter lag phase (indicating faster clotting initiation) was observed in patients with AA (8.8 [7.0-10.3]) compared to donors (11.8 [11.0-13.1]).
- While not detailed in the abstract, MP counts were also compared across groups.
Conclusions:
- Circulating membrane microparticles in patients with MI, AA, and IPAH exhibit enhanced procoagulant activity.
- Increased MP-driven coagulation may contribute to the thrombotic complications observed in these cardiovascular diseases.
- Further research is warranted to explore the clinical implications of elevated MP activity.
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