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

作者：Gheldof Damien; Haguet Helene; Dogne Jean Michel; Bouvy Celine; Graux Carlos; George Fabienne; Sonet Anne; Chatelain Christian; Chatelain Bernard; Mullier Francois

来源：Journal of Thrombosis and Thrombolysis, 2017, 43(2): 224-232.

DOI：10.1007/s11239-016-1471-z

• Extracellular vesicles
• Acute myeloid leukaemia
• Acute lymphoblastic leukaemia
• Thrombosis
• Tissue factor
• Microparticles
• Disseminated intravascular coagulation

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-TFA (R)). 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.

• 出版日期2017-2