title: Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia.
abstract: In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers.
authors.affiliation: Pediatric Department, University of Bari, Bari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Giordano
authors.forename: Angelo Claudio
authors.initials: AC
authors.lastname: Molinari
authors.forename: Giovanni Carlo
authors.initials: GC
authors.lastname: Del Vecchio
authors.forename: Paola
authors.initials: P
authors.lastname: Saracco
authors.forename: Giovanna
authors.initials: G
authors.lastname: Russo
authors.forename: Maria
authors.initials: M
authors.lastname: Altomare
authors.forename: Paolo
authors.initials: P
authors.lastname: Perutelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Crescenzio
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Domenico
authors.initials: D
authors.lastname: De Mattia
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000991:Antithrombins / Q000378:metabolism; D001215:Asparaginase / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects; D003561:Cytarabine / Q000009:adverse effects; D003630:Daunorubicin / Q000009:adverse effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D019007:P-Selectin / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D011241:Prednisone / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D019851:Thrombophilia / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology*; D054556:Venous Thromboembolism / Q000139:chemically induced; D014750:Vincristine / Q000009:adverse effects; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C029417:Von Willebrand antigen; C036309:fibrin fragment D; D014841:von Willebrand Factor; D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D013917:Thrombin; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin