title: Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.
abstract: 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.
authors.affiliation: Division of Rheumatology, University of Calgary, Calgary, Canada. paulmacmullan@rcsi.ie.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacMullan
authors.affiliation: Rheumatology Department, Mater Hospital, Dublin, Ireland. amadigan@mater.ie.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Madigan
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. nevinpaul@rcsi.ie.
authors.forename: Nevin
authors.initials: N
authors.lastname: Paul
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. apeace@rcsi.ie.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Peace
authors.affiliation: Department of Biochemistry, RCSI, Dublin, Ireland. abmalagha@rcsi.ie.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Alagha
authors.affiliation: Department of Biochemistry, RCSI, Dublin, Ireland. kbnolan@rcsi.ie.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Nolan
authors.affiliation: Rheumatology Department, Mater Hospital, Dublin, Ireland. g.mccarthy@ucd.ie.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: McCarthy
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. dkenny@rcsi.ie.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kenny
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D025242:Spondylarthropathies / Q000188:drug therapy*; D012460:Sulfasalazine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D012460:Sulfasalazine
keywords: Cardiovascular disease; DMARDs; Inflammation; Platelet function; Sulfasalazine