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Thromb Haemost 2026; 126(01): 037-048
DOI: 10.1055/a-2515-1402
Blood Cells, Inflammation and Infection

Factor VIIa–Antithrombin Complexes are Increased in Asthma: Relation to the Exacerbation-Prone Asthma Phenotype

Authors

  • Stanislawa Bazan-Socha 

    1   Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

  • Lucyna Mastalerz

    1   Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

  • Agnieszka Cybulska

    1   Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

  • Lech Zareba

    2   College of Natural Sciences, Institute of Computer Science, University of Rzeszow, Rzeszów, Poland

  • Bogdan Jakiela

    1   Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

  • Michal Zabczyk 

    3   Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

  • Teresa Iwaniec

    4   Department of Hematology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

  • Anetta Undas

    3   Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
    5   Centre for Medical Research and Technologies, The St. John Paul II Hospital, Krakow, Poland

Funding This project was funded by the Polish National Science Centre (No: DEC-2013/09/B/NZ5/00758).
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Graphical Abstract

Abstract

Background

Asthma is associated with a prothrombotic state. Plasma factor VIIa–antithrombin complex (FVIIa-AT) concentrations indirectly reflect the interaction of tissue factor (TF) with FVII. Since TF is a key initiator of coagulation in vivo, we hypothesized that FVIIa-AT concentrations are higher in asthma.

Methods

In 159 clinically stable adult asthma patients and 62 controls, we determined FVIIa-AT in plasma and analyzed their relation to circulating inflammatory and prothrombotic markers together with the total plasma potential for fibrinolysis (clot lysis time, CLT) and thrombin generation. We recorded clinical outcomes, including asthma exacerbations, during 3-year follow-up.

Results

Asthma patients were characterized by 38.5% higher FVIIa-AT (p < 0.001), related to bronchial obstruction (FEV1: r = −0.397, p < 0.001), asthma severity (r = 0.221, p = 0.005), and duration (r = 0.194, p = 0.015) compared to controls. FVIIa-AT showed weak positive associations with C-reactive protein (r = 0.208, p = 0.009), fibrinogen (r = 0.215, p = 0.007), and CLT (r = 0.303, p < 0.001) but not with thrombin generation parameters. In the follow-up (data obtained from 151 patients), we documented 151 severe asthma exacerbations in 51 (33.8%) patients, including 33 (21.9%) with ≥2 such events. Exacerbation-prone asthma phenotype was related to 13.1% higher FVIIa-AT (p = 0.012), along with asthma severity and control (p < 0.003, both). High FVIIa-AT (that is ≥100.1 pmol/L), defined on receiver operating characteristic curves, was linked to exacerbation-prone asthma phenotype (odds ratio 1.85; 95%CI: 1.23–2.80, p = 0.003) and shorter time to first exacerbation (p = 0.023).

Conclusion

This study is the first to show that FVIIa-AT concentrations are higher in asthma in relation to its severity and may help identify individuals at risk of the exacerbation-prone asthma phenotype.

Keywords

asthma - coagulation - inflammation - tissue factor - prothrombotic state

Data Availability Statement

The data sets are available from the corresponding author on a reasonable request.


Authors' Contribution

A.C., L.C., and S.B-S. recruited the patients and analyzed clinical data. L.M. and A.U. conceived and designed the study. T.I., B.J., and M.Z. performed the experiments and interpreted the laboratory data. L.Z. did statistical analysis. A.U. and S.B-S. interpreted all data. S.B-S., B.J., and A.U. drafted the manuscript; all the other authors revised it critically. All authors approved the final version of the manuscript and agreed to be responsible for their aspects of the work.


Supplementary Material



Publication History

Received: 09 October 2024

Accepted: 12 January 2025

Accepted Manuscript online:
13 January 2025

Article published online:
31 January 2025

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