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Investigation of the impact of antithrombin deficiency on the inflammatory response: Results from a single centre
Katarzyna Mayger1, Johanna Young2, Rui Leite3
1Synnovis Analytics, London, UK; Thrombosis & Haemophilia Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK; The University of Portsmouth, UK.
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.
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