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CME Evaluation

Oral Communication Session

Pediatric Hemostasis and Thrombosis

Session: Diagnostic tools to improve the care of pediatric hemostasis disorders

OC 72.5 - Global coagulation assays identify early changes in the coagulation potential of children with acute lymphoblastic leukemia

Wednesday, June 26, 2024
11:15 – 11:30 ICT
Room: Ballroom B3

    Co-Author(s)

  • CB

    Coralie Betticher

    Medical Student
    Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • Debora Bertaggia Calderara

    Research Associate
    Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • EM

    Elena Matthey Guirao

    Deputy Chief Technician
    Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • FG

    Francisco Javier Gomez

    Chief Technician
    Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • Alessandro Aliotta, PhD

    Research Associate
    Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Geneve, Switzerland

  • EL

    Elena Lemmel

    Study Coordinator
    Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • FC

    Francesco Ceppi

    Staff Physician
    Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

  • LA

    Lorenzo Alberio

    Chief Physician and Associate Professor
    Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
    Lausanne, Vaud, Switzerland

    • Presenting Author(s)

  • Mattia Rizzi, MD, PhD

    Staff Physician
    Pediatric Hematology-Oncology Unit - Pediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona (TI), Switzerland - Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanna (VD), Switzerland
    Le Mont sur Lausanne, Vaud, Switzerland

Background: Pediatric patients with acute lymphoblastic leukemia (ALL) are at highest risk for venous thromboembolism (VTE) during the induction phase of therapy (IT). These events are not predictable with routine coagulation test.

Aims: To identify children with ALL at high risk of VTE during IT using global coagulation assays (GCAs).

Methods: Blood from children with ALL (n=15) treated according the AIEOP-BFM protocol was collected at day (d) 0 (baseline) and during IT at d8-12 (before first dose PEG-Asparaginase), d22 (10 days after PEG-Asparaginase), d33 (end of IT). Ex vivo Thrombin Generation (TG) was measured with GCAs including the Calibrated-Automated-Thrombogram method (CAT), the automated-ST Genesia (STG), and the Thrombodynamics analyzer (TD). The latter enabled also to measure Fibrin-Clot-Formation (FCF). Additionally, in vivo TG markers (F1+2, TAT), and prothrombotic markers (D-dimers) were measured.

Results: Differently from in vivo TG markers, ex vivo GCAs identified increasing prothrombotic changes during IT. Specifically, TG measured with TD as expressed by Endogenous Thrombin Potential (ETP, nM thrombin*min) was significantly elevated already at d8-12 (p=0.0047) and continued to increase at d22 (p < 0.0001) and d33 (p < 0.001) as compared to d0, indicating a very early shift towards a procoagulant state. A similar pattern was observed for the rate of FCF (V, um/min: p=00021 at d8-12, p< 0.0001 at d22, and p=0.005 at d33). Remarkably, ETP measured with STG and TD was significantly higher (p=0.02 and p=0.04, respectively) already at day 8-12, i.e. well before clinical manifestation, in patients with VTE diagnosed after d22 (n=5), compared to patients without VTE.

Conclusion(s): GCAs and particularly TD and STG, captured early prothrombotic changes during IT in pediatric patients with ALL. GCAs may be able, alone or in combination with other clinical laboratory parameters, to identify children at high risk for thrombosis, who could profit from a primary pharmacological thromboprophylaxis.