title: Increased levels of tissue factor activity and procoagulant phospholipids during treatment of children with acute lymphoblastic leukaemia.
abstract: The use of L-asparaginase (L-ASP) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with thrombotic complications. We evaluated the activities of tissue factor (TFa), thrombomodulin (TMa) and procoagulant phospholipids (PPL) in 26 consecutive children with ALL (25 B-ALL and one T-ALL) treated by the French Acute Lymphoblastic Leukemia group (FRALLE)-2000 protocol. Samples were obtained at diagnosis, after glucocorticoid (GC) therapy, during the induction phase with L-ASP, vincristine (VCR) and adriamycin (ADR), during the re-induction and within the week after treatment. Plasma levels of TFa, TMa and PPL increased gradually and significantly during the different phases of the treatment, with higher levels observed during the induction period, and decreased after treatment discontinuation. In vitro studies showed that the different drugs used for ALL treatment could induce a weak expression of TF and procoagulant activity (PCA) on normal and leukaemia blood cells, while a marked effect was observed on endothelial cells. In conclusion, these data indicate that, in addition to the well-identified increased in coagulation factors and inhibitor deficiencies, the injury of the endothelium could lead to the release of TF and PPL and could contribute to the hypercoagulability of children treated for ALL.
authors.affiliation: Paediatric Haematology and Oncology & IHU, Rouen University Hospital, rue de Germont, Rouen, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Schneider
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dreden
authors.forename: Aurélie
authors.initials: A
authors.lastname: Rousseau
authors.forename: Yusra
authors.initials: Y
authors.lastname: Kassim
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Legrand
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.forename: Marc
authors.initials: M
authors.lastname: Vasse
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010743:Phospholipids / Q000097:blood*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D001779:Blood Coagulation Factors; D010743:Phospholipids; C546931:THBD protein, human; D018180:Thrombomodulin; D013925:Thromboplastin