PB0884 - Investigation of the impact of antithrombin deficiency on the inflammatory response: Results from a large, single centre cohort study in the UK

Background: Antithrombin is key in regulating haemostasis by inhibiting procoagulant proteases. Existing evidence suggests antithrombin signalling functions may exert an anti-inflammatory effect. We hypothesised that individuals with Inherited Antithrombin Deficiency (IAD) may have evidence of an increased inflammatory state.

Aims: To assess the inflammatory state in those with IAD and compare with healthy controls (HC), by measuring inflammatory markers.

Methods: Ethics approval was granted by NHS REC UK (ref: 21/NW/0162), all participants gave written informed consent. Case-control study of age- and sex-matched healthy individuals with patients with IAD (Table 1). ELISA assays were used to quantify Prothrombin Fragment 1+2 (PF1+2) (Enzygnost, Siemens, Germany) and proinflammatory markers: intercellular adhesions molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) (Bio-Techne, Abington, UK) and complement C3a (MicroVue, Quidel, US). Biomarkers of NETosis were measured using a chemiluminescence immunoassay (Nu.Q®NETs) utilising an anti-histone antibody to capture Neutrophil Extracellular Traps (NETs) on IDS-i10 analyser (Immunodiagnostic Systems Ltd, UK). Statistical analysis was performed using SPSS v27.

Results: Initial analysis including all IAD showed significantly higher levels of NETs compared with HCs (p=0.012). No significant differences were observed for C3a, VCAM and ICAM between HC and IAD (Table 2). IAD patients were separated into two groups based on the history of VTE. As expected, PF1+2 levels were decreased in those with a previous VTE receiving anticoagulation (171) when compared with HC (196, p=0.069). Anticoagulation had no effect on levels of inflammatory markers. Elevated levels of NETs (37, p=0.004), VCAM-1 (855, p=0.022) and complement C3a (69, p=0.034) were observed in the IAD group with a history of VTE compared with HCs.

Conclusion(s): We found little evidence that those with IAD had an abnormal inflammatory state as measured by a group of biomarkers but found evidence of increased markers in those with previous VTE and will assess this in non IAD patients with previous VTE.