Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.

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 anti-platelet 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.