MacMullan Paul A, Madigan Anne M, Paul Nevin, Peace Aaron J, Alagha Ahmed, Nolan Kevin B, McCarthy Geraldine M, Kenny Dermot
Division of Rheumatology, University of Calgary, Calgary, Canada.
Rheumatology Department, Mater Hospital, Dublin, Ireland.
Clin Rheumatol. 2016 Feb;35(2):447-55. doi: 10.1007/s10067-014-2769-x. Epub 2014 Sep 26.
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.
本研究的目的是评估柳氮磺胺吡啶及其代谢产物对炎性关节炎（IA）患者血小板功能的影响。对135例确诊为IA的连续患者进行了筛查。排除有心血管疾病（CVD）病史、正在服用抗血小板药物或非甾体抗炎药（NSAIDs）的患者。共对32例患者进行了研究，其中15例服用柳氮磺胺吡啶，17例服用其他改善病情抗风湿药物（DMARDs）且未服用柳氮磺胺吡啶。将这两组与15例长期服用阿司匹林的稳定CVD患者进行比较。还在健康供者的样本（n = 18）中体外测试了柳氮磺胺吡啶及其代谢产物对花生四烯酸（AA）诱导的血小板聚集的影响。柳氮磺胺吡啶组和其他DMARD组的人口统计学、CVD危险因素和疾病活动指数相似。柳氮磺胺吡啶组中AA诱导的血小板聚集受到显著抑制（9±7%），与阿司匹林组（10±6%）相当。相比之下，其他DMARDs组中AA诱导的血小板聚集没有受到影响（77±12%）（p < 0.001）。此外，柳氮磺胺吡啶治疗对多种其他激动剂诱导的血小板聚集没有影响。柳氮磺胺吡啶及其代谢产物（5-氨基水杨酸和磺胺吡啶）在体外对AA诱导的血小板聚集发挥了相加和剂量依赖性的抑制作用（p < 0.001）。柳氮磺胺吡啶对AA诱导的血小板聚集的抑制作用与阿司匹林相当，且依赖于柳氮磺胺吡啶及其代谢产物。这代表了一种可能有助于柳氮磺胺吡啶对IA患者已知心脏保护作用的潜在机制。
