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

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.