Perneby Christina, Wallén N Håkan, Rooney Cathy, Fitzgerald Desmond, Hjemdahl Paul
Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), SE-171 76 Stockholm, Sweden.
Thromb Haemost. 2006 Apr;95(4):652-8.
Aspirin is widely used, but dosages in different clinical situations and the possible importance of "aspirin resistance" are debated. We performed an open cross-over study comparing no treatment (baseline) with three aspirin dosage regimens--37.5 mg/day for 10 days, 320 mg/day for 7 days, and, finally, a single 640 mg dose (cumulative dose 960 mg)--in 15 healthy male volunteers. Platelet aggregability was assessed in whole blood (WB) and platelet rich plasma (PRP). The urinary excretions of stable thromboxane (TxM) and prostacyclin (PGI-M) metabolites, and bleeding time were also measured. Platelet COX inhibition was nearly complete already at 37.5 mg aspirin daily, as evidenced by >98% suppression of serum thromboxane B2 and almost abolished arachidonic acid (AA) induced aggregation in PRP 2-6 h after dosing. Bleeding time was similarly prolonged by all dosages of aspirin. Once daily dosing was associated with considerable recovery of AA induced platelet aggregation in WB after 24 hours, even after 960 mg aspirin. Collagen induced aggregation in WB with normal extracellular calcium levels (hirudin anticoagulated) was inhibited <40% at all dosages. TxM excretion was incompletely suppressed, and increased <24 hours after the cumulative 960 mg dose. Aspirin treatment reduced PGI-M already at the lowest dosage (by approximately 25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplatelet effects of aspirin are limited in WB with normal calcium levels. Since recovery of COX-dependent platelet aggregation occurred within 24 hours, once daily dosing of aspirin might be insufficient in patients with increased platelet turnover.
阿司匹林被广泛使用，但不同临床情况下的剂量以及“阿司匹林抵抗”的潜在重要性仍存在争议。我们进行了一项开放交叉研究，在15名健康男性志愿者中比较了无治疗（基线）与三种阿司匹林剂量方案——10天内每天37.5毫克、7天内每天320毫克，最后是单次640毫克剂量（累积剂量960毫克）。在全血（WB）和富血小板血浆（PRP）中评估血小板聚集性。还测量了稳定血栓素（TxM）和前列环素（PGI-M）代谢物的尿排泄量以及出血时间。每日37.5毫克阿司匹林时血小板COX抑制作用几乎已完全，给药后2 - 6小时血清血栓素B2抑制率>98%以及PRP中花生四烯酸（AA）诱导的聚集几乎被消除可证明这一点。所有剂量的阿司匹林均同样延长出血时间。即使在服用960毫克阿司匹林后，每日一次给药24小时后WB中AA诱导的血小板聚集仍有相当程度的恢复。在细胞外钙水平正常（水蛭素抗凝）的WB中，所有剂量下胶原诱导的聚集抑制率<40%。TxM排泄未被完全抑制，在累积960毫克剂量后<24小时增加。阿司匹林治疗在最低剂量时就已降低PGI-M（约25%），但PGI-M排泄与血小板聚集性不相关。在细胞外钙水平正常的WB中，阿司匹林的抗血小板作用有限。由于COX依赖的血小板聚集在24小时内恢复，对于血小板周转率增加的患者，每日一次服用阿司匹林可能不足。
