Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia.

Gheldof, Damien;Haguet, Hélène;Dogné, Jean-Michel;Bouvy, Céline;Mullier, François;et.al.
(2017) Journal of Thrombosis and Thrombolysis : an international journal for clinicians and scientists — Vol. 43, n° 2, p. 224-232 (2017)

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Authors
  • Gheldof, DamienUNamur
    Author
  • Haguet, HélèneUNamur
    Author
  • Dogné, Jean-Michel
    Author
  • Bouvy, CélineUCLouvain
    Author
  • Graux, CarlosUCLouvain
    Author
  • George, FabienneUCLouvain
    Author
  • Sonet, AnneUCLouvain
    Author
  • Chatelain, ChristianUCLouvain
    Author
  • Chatelain, BernardUCLouvain
    Author
  • Mullier, FrançoisUCLouvain
    Author
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Abstract
Haemostatic complication is common for patients with hematologic malignancies. Recent studies suggest that the procoagulant activity (PCA) of extracellular vesicles (EV) may play a major role in venous thromboembolism and disseminated intravascular coagulation (DIC) in acute leukaemia. To study the impact of EVs from leukaemic patients on thrombin generation and to assess EV-PCA as a potential biomarker for thrombotic complications in patients with acute leukaemia. Blood samples from a cohort of patients with newly diagnosed acute leukaemia were obtained before treatment (D-0), 3 and 7 days after treatment (D-3 and D-7). Extracellular vesicles were isolated and concentrated by ultracentrifugation. EV-PCA was assessed by thrombin generation assay, and EV-associated tissue factor activity was measured using a commercial bio-immunoassay (Zymuphen MP-TF®). Of the 53 patients, 6 had increased EV-PCA at D-0 and 4 had a thrombotic event. Patients without thrombotic events (n = 47) had no elevated EV-PCA. One patient had increased EVs with procoagulant activity at D-3 and developed a DIC at D-5. This patient had no increased EVs-related tissue factor activity from D-0 to D-7 (<2 pg/ml). Eight patients had increased EVs with tissue factor activity (>2 pg/ml), of these, four had a thrombosis and two had haemorrhages. Procoagulant activity of extracellular vesicles could have a predictive value in excluding the risk of thrombotic events. Our findings also suggest a possible association between thrombotic events and EV-PCA.
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Gheldof, D., Haguet, H., Dogné, J.-M., Bouvy, C., Graux, C., George, F., Sonet, A., Chatelain, C., Chatelain, B., & Mullier, F. (2017). Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia. Journal of Thrombosis and Thrombolysis : an international journal for clinicians and scientists, 43(2), 224-232. https://doi.org/10.1007/s11239-016-1471-z (Original work published 2017)