Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target

Objective. To assess the influence of disease activity on platelet function in patients with inflammatory arthritis (IA). Methods. Ninety-six patients with an established diagnosis of IA (RA, PsA, seronegative SpA) were recruited. Patients with a history of cardiovascular disease (CVD), diabetes mellitus or receiving antiplatelet therapy were excluded. Demographic data, traditional CVD risk factors and medication use were recorded. Patients were characterized as active disease (n = 38) or control disease (n = 58) groups, respectively, based on internationally validated measures of disease activity [comprising serological markers (ESR, CRP, fibrinogen), patient measures (visual analogue scale of disease activity), evaluator global assessment and the 28-joint disease activity score]. Platelet function was assessed using a novel assay of platelet reactivity. Platelet aggregation to multiple concentrations of arachidonic acid, collagen, epinephrine, thrombin receptor activating peptide and adenosine diphosphate (ADP) were measured simultaneously using a modification of light transmission aggregometry. Results. The two groups (active vs control) were similar in terms of demographics and CVD risk factors. Anti-TNF-alpha therapy use was higher in the control group (P = 0.004), whereas NSAID use was higher in the active group (P = 0.001). There was a significant difference between the two groups in platelet response to ADP (P < 0.001). Platelet aggregation, in response to submaximal concentrations of ADP, was increased in the active disease group compared with the control group. There was no difference in platelet reactivity between the groups in response to any of the other agonists. Conclusion. Patients with active IA demonstrate enhanced platelet reactivity, unique to the ADP pathway. This potential pro-thrombotic bias may contribute to their increased cardiovascular risk.