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Screening for Coagulopathy and Identification of Children With Acute Lymphoblastic Leukemia at a Higher Risk of Symptomatic Venous Thrombosis: An AIEOP Experience

Santoro, Nicola MD*; Colombini, Antonella MD; Silvestri, Daniela MSc; Grassi, Massimo MD*; Giordano, Paola MD*; Parasole, Rosanna MD§; Barisone, Elena MD; Caruso, Roberta MD; Conter, Valentino MD†,#; Valsecchi, Maria G. PhD; Masera, Giuseppe MD; Rizzari, Carmelo MD

Journal of Pediatric Hematology/Oncology: July 2013 - Volume 35 - Issue 5 - p 348–355
doi: 10.1097/MPH.0b013e31828dc614
Original Articles

Introduction: Venous thromboembolic events (VTEs) are frequent complications of childhood acute lymphoblastic leukemia (ALL) treatment. The aim of the study was to evaluate the rate of symptomatic VTEs in children with ALL and the predictive value of clinical and biological factors and routine monitoring of coagulation parameters in identifying children at a higher risk of this complication.

Materials and Methods: Between September 2000 and July 2006, 2042 children (≥1 and younger than 18 y) with newly diagnosed ALL were enrolled in Italy in the AIEOP (Italian Association of Pediatric Hematology and Oncology)-BFM (Berlin-Frankfurt-Muenster) ALL 2000 trial. Patients with symptomatic VTEs (deep venous thromboses or cerebral venous thromboses) were identified after a careful review of clinical records. The impact of coagulation derangement at the onset of VTEs was evaluated by a nested case-control study.

Results: Forty-eight (2.4%) children presented with a VTE. The rate of VTEs was higher in male patients (P=0.001); patients randomized to receive dexamethasone tended to have a higher rate of VTE compared with those who received prednisone (P=0.10). The coagulation derangement at the onset of VTE was not associated with VTE occurrence. The prevalence of a factor V Leiden G1691A mutation and the prothrombin G20210A variant was higher in children with VTE than that expected in the general population.

*Department of Pediatrics, Division of Pediatric Hematology and Oncology, Ospedale Policlinico “Consorziale,” University of Bari, Bari

Department of Pediatrics, University of Milano-Bicocca, Ospedale S Gerardo, Monza

Center of Biostatistics for Clinical Epidemiology, Department of Health Sciences, University of Milano-Bicocca, Milan

§Department of Pediatric Hemato-Oncology, Ospedale Pausillipon, Napoli

Department of Pediatric Hemato-Oncology, Ospedale Infantile Regina Margherita, Turin

Department of Pediatric Hemato-Oncology, Children’s Hospital and Research Institute “Bambino Gesù,” Rome

#Department of Pediatrics, Ospedali Riuniti, Bergamo, Italy

M.G.V. was partially supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). The authors declare no conflict of interest.

Reprints: Carmelo Rizzari, MD, Department of Pediatrics, University of Milano-Bicocca, Hospital S. Gerardo, Via Pergolesi 33, 20052 Monza (MI), Italy (e-mail:

Received February 8, 2012

Accepted February 17, 2013

© 2013 by Lippincott Williams & Wilkins.