Investigation of the impact of antithrombin deficiency on the inflammatory response: Results from a single centre cohort study

Background

Antithrombin signalling may exert an anti-inflammatory effect; therefore we hypothesised that individuals with inherited antithrombin deficiency (ATD) may have an altered inflammatory state.

Aims

To assess the inflammatory state in those with ATD compared with healthy controls (HCs), by measuring inflammatory markers.

Methods

A case-control study of age- and sex-matched HCs (n = 51) with ATD patients (n = 51). Seven inflammatory makers were selected. ELISA assays quantified: high-sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and complement C3a-des-Arg. Circulating nucleosomes were measured using a chemiluminescence immunoassay (Nu.Q®NETs). Clauss fibrinogen and HemosIL VWF activity were also measured. Results are expressed as median (range).

Results

Overall analysis of ATD vs HCs showed elevated circulating nucleosomes 29.3 ng/mL [0.5–309.3] vs 21.3 ng/mL [3.7–86.3], p = 0.012 but no differences were observed for C3a, VCAM-1, ICAM-1, VWF and fibrinogen. ATD patients were separated into two groups based on the history of VTE. PF1 + 2 levels were decreased in ATD with previous VTE due to anticoagulation. Increased circulating nucleosomes 38.4 ng/mL [11.6–309.3] vs 24.2 ng/mL [9.3–46.5], p = 0.003 and VCAM-1858.3 ng/mL [564.4–2483.2] vs 746.2 ng/mL [460.6–1034.8], p = 0.016 was observed in ATD with previous VTE vs HCs, respectively. Decreased ICAM-1 and VWF levels were noted in the ATD with no history of VTE when compared to HCs. No significant relationships between AT activity and inflammatory markers were found.

Conclusion

Those with ATD did not have an altered inflammatory state as measured by a group of biomarkers except for increased circulating nucleosomes and VCAM-1 compared to paired healthy controls which can be attributed to previous VTE; while those with no personal history of VTE had reduced ICAM-1 and VWF. No correlation was observed between AT activity and levels of inflammatory markers.