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Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability

Aleman, MM; Gardiner, C; Harrison, P; Wolberg, AS; (2011) Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability. Journal of Thrombosis and Haemostasis , 9 (11) pp. 2251-2261. 10.1111/j.1538-7836.2011.04488.x. Green open access

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Abstract

BACKGROUND: Microparticles (MPs) are sub-micron vesicles shed by activated or apoptotic cells, including platelets and monocytes. Increased circulating MPs are associated with thrombosis; however, their role in thrombogenesis is poorly understood. OBJECTIVE: To determine how MPs promote thrombin generation and modulate fibrin density and stability. METHODS: Platelets and monocytes were isolated from healthy donors. Platelets were stimulated with calcium ionophore, thrombin receptor agonist peptide (TRAP) or TRAP/convulxin. Monocytes and human monocytic THP-1 cells were stimulated with lipopolysaccharide (LPS). MPs were isolated, washed by high-speed centrifugation and assessed using the following: transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA), flow cytometry, tissue factor (TF) activity, prothrombinase activity, thrombin generation, and clot formation, density and stability. RESULTS: MPs from monocytes (M-MPs) and platelets (PMPs) had similar shapes and diameters (100-300 nm). M-MPs had TF activity (16.7 ± 2.4 pm TF per 10(6) MP), supported prothrombinase activity and triggered shorter thrombin generation lag times than buffer controls (5.4 ± 0.5 vs. 84.2 ± 4.8 min, respectively). Compared with controls, M-MPs supported faster fibrin formation (0.24 ± 0.24 vs. 76.7 ± 15.1 mOD min(-1) , respectively), 38% higher fibrin network density and higher clot stability (3.8-fold higher turbidity in the presence of tissue plasminogen activator). In contrast, PMPs did not have TF activity and supported 2.8-fold lower prothrombinase activity than M-MPs. PMPs supported contact-dependent thrombin generation, but did not independently increase fibrin network density or stability. Interestingly, PMPs increased rates of thrombin generation and fibrin formation (1.7- and 1.3-fold, respectively) when mixed with THP-1-derived MPs. CONCLUSION: MPs from platelets and monocytes differentially modulate clot formation, structure and stability, suggesting unique contributions to thrombosis.

Type: Article
Title: Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/j.1538-7836.2011.04488.x
Publisher version: http://doi.org/10.1111/j.1538-7836.2011.04488.x
Language: English
Keywords: fibrinogen, microparticle, phosphatidylserine, thrombosis, tissue factor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1468247
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