title: Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia.
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.
authors.affiliation: Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium. gheldofdamien@gmail.com.
authors.forename: Damien
authors.initials: D
authors.lastname: Gheldof
authors.affiliation: Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Haguet
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouvy
authors.affiliation: Biobank, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium.
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.affiliation: Biobank, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: George
authors.affiliation: Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium.|Université catholique de Louvain, CHU UCL Namur, Haematology Department, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Sonet
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Chatelain
authors.affiliation: Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.affiliation: Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium.|Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, University of Namur, Namur, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Mullier
mesh_terms: D000208:Acute Disease; D015415:Biomarkers; D001777:Blood Coagulation; D015331:Cohort Studies; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000209:etiology*; D000067128:Extracellular Vesicles / Q000473:pathology / Q000502:physiology*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012306:Risk; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D013917:Thrombin
keywords: Acute lymphoblastic leukaemia; Acute myeloid leukaemia; Disseminated intravascular coagulation; Extracellular vesicles; Microparticles; Thrombosis; Tissue factor