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CME Evaluation

Oral Communication Session

Venous Thromboembolism

Session: Cancer associated thrombosis - Mechanisms

OC 12.2 - Activated FXI-antithrombin complex predicts venous thromboembolism (VTE) in a large prospective cohort of non-small cell lung cancer (NSCLC) patients

Sunday, June 23, 2024
09:45 – 10:00 ICT
Room: Ballroom B2

    Presenting Author(s)

  • Patricia Gomez Rosas, MD

    PhD candidate
    Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

    • Co-Author(s)

  • Marina Marchetti

    MSc, PhD
    Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII,Bergamo
    Bergamo, Lombardia, Italy

  • Magdolna Nagy

    PhD
    Department of Biochemistry, Maastricht University Medical Center+, Maastricht, The Netherlands
    Maastricht, Limburg, Netherlands

  • Henri M.H Spronk, PhD

    Professor of Biochemistry of Atherothrombosis
    Maastricht University
    Maastricht, Limburg, Netherlands

  • CV

    Cristina Verzeroli

    Biologist
    Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • LR

    Laura Russo

    MSc
    Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • SG

    Sara Gamba

    Biologist
    Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • CT

    Carmen Julia Tartari

    Biologist
    Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • SB

    Silvia Bolognini

    Biologist
    Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • CT

    Chiara Ticozzi

    MSc
    Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII,Bergamo
    Bergamo, Lombardia, Italy

  • FS

    Francesca Schieppati

    MD
    Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • AD

    Andrea D'Alessio

    MD
    Medical Oncology and Internal Medicine, Policlinico San Marco, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • RL

    Roberto Labianca

    MD
    Fondazione ARTET Onlus
    Bergamo, Lombardia, Italy

  • Hugo ten Cate, MD, PHD

    MD, PhD
    Departments of Internal Medicine and Biochemistry, Maastricht University Medical Center+, Maastricht, The Netherlands
    Maastricht, Limburg, Netherlands

  • Anna Falanga, MD PhD

    MD, PhD, Prof
    University of Milano Bicocca, School of Medicine, Monza, Italy
    Bergamo, Lombardia, Italy

  • OH

    On behalf HYPERCAN study

    MD
    HYPERCAN study
    Bergamo, Lombardia, Italy

Background: NSCLC patients are at high risk of VTE, especially during chemotherapy. Despite the contact system is implicated in the pathogenesis of thrombosis, few data are available on contact system studies in NSCLC-associated VTE.

Aims: In a prospective cohort of NSCLC patients starting chemotherapy, we measured the levels of biomarkers of contact activation and assessed whether they can help in predicting VTE (HYPERCAN study) within 6 months after starting chemotherapy.

Methods: Prechemotherapy plasma samples were tested by ELISA for in vivo biomarkers of contact pathway activation (i.e., plasma kallikrein:C1-esterase inhibitor [PKa:C1Inh], FXIa:antithrombin [FXIa:AT], FXIa:C1Inh, activated factor IX:AT [FIXa:AT]), and thrombin generation (i.e., prothrombin fragment 1+2 [F1+2], thrombin-antithrombin complex [TAT]). Clinical data and VTE were recorded prospectively.

Results: 719 (489M/230F, median age: 66 years) newly diagnosed NSCLC patients (568 metastatic and 151 locally advanced) were studied. The 6-month VTE cumulative incidence was 10% (12% in metastatic and 4% in locally advanced group). Patients who developed VTE (n=68) had significantly higher (p < 0.001) basal levels of FXIa:AT complex, F1+2, and TAT, compared to VTE-free patients, also after age and gender correction. The multivariable analysis identified FXIa:AT [HR 1.18 (95%CI 1.02-1.39)] and TAT [HR 1.30 (95%CI 1.08-1.57)] as VTE independent risk factors during chemotherapy. Furthermore, by KM analysis, patients with FXIa:AT and TAT values above the highest quartile showed significantly higher VTE incidence than patients with values below the 3rd quartile (23% vs 8%, log-rank < 0.001).

Conclusion(s): Elevated contact pathway activation was observed in NSCLC patients who developed VTE. This finding has implications for the use of FXIa inhibitors for thromboprophylaxis in this setting. In addition, a score based on both FXIa:AT and TAT was generated to identify those patients at higher risk of VTE.