title: Microparticle bearing tissue factor: a link between promyelocytic cells and hypercoagulable state.
abstract: Patients with hematological malignancies have a 28-fold increased risk of venous thromboembolism (VTE). Among patients with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE is 5.2%. Several studies suggest that microvesicles (MVs) harboring TF may play a role in VTE and disseminated intravascular coagulation (DIC) in acute promyelocytic leukemia (APL). The aim of this study was to assess the capacity of untreated (APL) cells to shed procoagulant MVs. APL cells (NB4 and HL-60 cell lines) and MVs were separated by filtration (0.1-0.22-0.45-0.65 μm). The procoagulant activity (PCA) was assessed by thrombin generation assay (TGA). Alternatively, MVs were incubated with anti-Tissue Factor (TF) antibodies, with annexin V to assess the contribution of TF and phospholipids (PL) to the PCA, respectively. NB4 cells had a high PCA mainly triggered by MVs of size under 0.45 μm. The PCA of MVs was related to the expression of active TF and PL. HL-60 cells had a weaker PCA since TF is mostly present in its inactive form. Moreover, HL-60 do not produce MVs<0.65 μm associated with PCA. MVs could have a predicting value for VTE and DIC in patients with acute promyelocytic leukemia and could inform physicians about the optimal use of a thromboprophylaxis.
authors.affiliation: Hematology Laboratory, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium. Electronic address: gheldofdamien@gmail.com.
authors.forename: Damien
authors.initials: D
authors.lastname: Gheldof
authors.affiliation: Hematology Laboratory, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium; Department of Pharmacy, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.affiliation: Hematology Laboratory, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bailly
authors.affiliation: Hematology, CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Devalet
authors.affiliation: Department of Pharmacy, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.affiliation: Hematology Laboratory, NARILIS, Namur Thrombosis and Hemostasis Center (NTHC), CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.affiliation: Hematology, CHU UCL Mont-Godinne-Dinant, Université Catholique de Louvain, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Chatelain
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003630:Daunorubicin / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D019851:Thrombophilia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D054556:Venous Thromboembolism / Q000097:blood / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D013925:Thromboplastin; D003630:Daunorubicin
keywords: AMLM3; Leukemia; Microvesicles; Thrombosis; Tissue factor