Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia

Paola Giordano, Angelo Claudio Molinari, Giovanni Carlo Del Vecchio, Paola Saracco, Giovanna Russo, Maria Altomare, Paolo Perutelli, Nicoletta Crescenzio, Nicola Santoro, Marina Marchetti, Domenico De Mattia, Anna Falanga

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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-α), 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.

Original languageEnglish
Pages (from-to)325-330
Number of pages6
JournalAmerican Journal of Hematology
Volume85
Issue number5
DOIs
Publication statusPublished - May 2010

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Hemostatics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
P-Selectin
Prospective Studies
Plasminogen Activator Inhibitor 1
Venous Thromboembolism
von Willebrand Factor
Drug Therapy
Thrombin
Interleukin-6
Tumor Necrosis Factor-alpha
Molecular Weight
Therapeutics
Remission Induction
Antithrombins
Vascular Endothelium
Fibrinolysis
Fibrin
Fibrinogen
Biomarkers

ASJC Scopus subject areas

  • Hematology

Cite this

Giordano, P., Molinari, A. C., Del Vecchio, G. C., Saracco, P., Russo, G., Altomare, M., ... Falanga, A. (2010). Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. American Journal of Hematology, 85(5), 325-330. https://doi.org/10.1002/ajh.21665

Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. / Giordano, Paola; Molinari, Angelo Claudio; Del Vecchio, Giovanni Carlo; Saracco, Paola; Russo, Giovanna; Altomare, Maria; Perutelli, Paolo; Crescenzio, Nicoletta; Santoro, Nicola; Marchetti, Marina; De Mattia, Domenico; Falanga, Anna.

In: American Journal of Hematology, Vol. 85, No. 5, 05.2010, p. 325-330.

Research output: Contribution to journalArticle

Giordano, P, Molinari, AC, Del Vecchio, GC, Saracco, P, Russo, G, Altomare, M, Perutelli, P, Crescenzio, N, Santoro, N, Marchetti, M, De Mattia, D & Falanga, A 2010, 'Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia', American Journal of Hematology, vol. 85, no. 5, pp. 325-330. https://doi.org/10.1002/ajh.21665
Giordano, Paola ; Molinari, Angelo Claudio ; Del Vecchio, Giovanni Carlo ; Saracco, Paola ; Russo, Giovanna ; Altomare, Maria ; Perutelli, Paolo ; Crescenzio, Nicoletta ; Santoro, Nicola ; Marchetti, Marina ; De Mattia, Domenico ; Falanga, Anna. / Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. In: American Journal of Hematology. 2010 ; Vol. 85, No. 5. pp. 325-330.
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