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Determination of the Procoagulant Activity of Extracellular Vesicle (EV) Using EV-Activated Clotting Time (EV-ACT)
Published on: August 4, 2023
Phospholipid-dependent procoagulant activity is highly expressed by circulating microparticles in patients with
Marina Marchetti1, Carmen J Tartari, Laura Russo
1Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
Abstract:
This study evaluates the functional procoagulant features of plasma microparticle (MP) to explore the MP contribution to the hypercoagulable state of patients with essential thrombocythemia (ET). Platelet-free plasma samples were obtained from 73 ET patients (37 positive for the JAK2V617F mutation) and 72 control subjects. The calibrated automated thrombogram (CAT) was performed in plasma samples to determine thrombin generation of MP-associated tissue factor (TF) and procoagulant phospholipid (PPL) activity, and the STA Procoag PPL assay to measure MP-PPL activity only. Both thrombin generation and PPL procoagulant activities were found significantly elevated in ET patients compared to controls, and were associated to significantly higher levels of TF antigen and FVIIa/AT complex. Thrombin generation was significantly greater in JAK2-V617F positive compared to JAK2-V617F negative patients and normal subjects. Significant correlations were found between the PPL-assay and the different parameters of the CAT assay. No difference was seen between the thrombosis and no thrombosis group. Prospective studies are needed to test whether MP-associated thrombin generation and procoagulant activity may predict for thrombosis in these patients.
Insights
Plasma microparticles (MPs) significantly contribute to hypercoagulability in essential thrombocythemia (ET). Elevated thrombin generation and procoagulant activity in ET patients, particularly those with JAK2V617F mutation, warrant further investigation for thrombosis prediction.
Area of Science:
- Hematology
- Thrombosis Research
- Molecular Biology
Background:
- Essential thrombocythemia (ET) is characterized by a hypercoagulable state.
- Plasma microparticles (MPs) are implicated in hemostasis and thrombosis.
- The specific contribution of MPs to ET-related hypercoagulability requires further elucidation.
Purpose of the Study:
- To evaluate the functional procoagulant features of plasma microparticles (MPs) in ET patients.
- To explore the role of MPs in the hypercoagulable state of ET.
- To investigate the association between MP activity, JAK2V617F mutation, and thrombosis.
Main Methods:
- Plasma samples from 73 ET patients and 72 controls were analyzed.
- Calibrated automated thrombogram (CAT) assessed thrombin generation and MP-associated tissue factor (TF) and procoagulant phospholipid (PPL) activity.
- STA Procoag PPL assay measured MP-PPL activity.
- JAK2V617F mutation status was determined.
Main Results:
- ET patients exhibited significantly elevated thrombin generation and PPL procoagulant activities compared to controls.
- These activities correlated with higher levels of TF antigen and FVIIa/AT complex.
- Thrombin generation was markedly greater in JAK2V617F-positive ET patients.
Conclusions:
- Plasma microparticles possess functional procoagulant activity that contributes to the hypercoagulable state in ET.
- Elevated MP activity, particularly in JAK2V617F-positive patients, highlights their role in ET pathogenesis.
- Further prospective studies are needed to determine if MP-associated thrombin generation predicts thrombosis risk in ET.
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