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. 2025 Jun;23(6):1908-1919.
doi: 10.1016/j.jtha.2025.02.029. Epub 2025 Mar 6.

Activated factor XI-antithrombin and thrombin-antithrombin complexes in the prediction of venous thromboembolism and mortality in patients with non-small-cell lung cancer

Patricia Gomez-Rosas  1 , Magdolna Nagy  2 , Henry M H Spronk  2 , Laura Russo  3 , Sara Gamba  3 , Carmen Julia Tartari  3 , Silvia Bolognini  3 , Chiara Ticozzi  3 , Francesca Schieppati  3 , Roberta Sarmiento  4 , Filippo De Braud  5 , Giovanna Masci  6 , Carlo Tondini  7 , Fausto Petrelli  8 , Francesco Giuliani  9 , Andrea D'Alessio  10 , Armando Santoro  6 , Giampietro Gasparini  4 , Roberto Labianca  11 , Hugo Ten Cate  2 , Anna Falanga  12 , Marina Marchetti  13 ; HYPERCAN Investigators
Collaborators, Affiliations

Activated factor XI-antithrombin and thrombin-antithrombin complexes in the prediction of venous thromboembolism and mortality in patients with non-small-cell lung cancer

Patricia Gomez-Rosas et al. J Thromb Haemost. 2025 Jun.

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) are at high risk of venous thromboembolism (VTE), especially during chemotherapy. Even though the contact system is implicated in the pathogenesis of thrombosis, limited data are available on the role of contact system activation in NSCLC-associated VTE.

Objectives: In a prospective cohort of patients with NSCLC starting chemotherapy, contact system activation and thrombin generation biomarkers were assessed in relation to 6-month VTE occurrence and mortality.

Methods: Prechemotherapy plasma samples of 719 newly diagnosed patients with NSCLC were tested for in vivo biomarkers of contact system activation (ie, kallikrein [pKa]:antithrombin [AT; PKa:AT], activated factor [F]XI:AT [FXIa:AT], FXIa:C1-esterase inhibitor C1Inh [FXIa:C1Inh], activated FIX:AT [FIXa:AT]), and thrombin generation (ie, prothrombin fragment 1+2 [F1+2] and thrombin-antithrombin complex [TAT]). Clinical data, VTE, and mortality were recorded prospectively.

Results: The 6-month VTE and mortality cumulative incidences were 11% and 27%, respectively. Basal levels of FXIa:AT complexes, F1+2, and TAT were higher in patients who developed VTE than those in VTE-free patients. Differently, PKa:AT, FIXa:AT, and TAT were lower in survivors than those in nonsurvivors. The multivariable analysis identified FXIa:AT (subdistribution hazard ratio, 1.17; 95% CI, 1.00-1.37) and TAT (subdistribution hazard ratio, 1.28; 95% CI, 1.10-1.50) as VTE-independent risk factors during chemotherapy. A score based on these biomarkers was generated, which was able to discriminate patients at significantly higher rates of VTE and mortality.

Conclusion: Elevated in vivo contact pathway activation and thrombin generation were observed in patients with NSCLC who developed VTE. Furthermore, a score based on both FXIa:AT and TAT levels was developed to identify those patients at higher risk of VTE and mortality.

Keywords: cancer-associated thrombosis; contact systemcoagulation; non–small-cell lung cancer–associated venous thromboembolism; thrombin generation.

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Declaration of competing interests The authors declare no conflict of interest.

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