Helgason C M, Bolin K M, Hoff J A, Winkler S R, Mangat A, Tortorice K L, Brace L D
University of Illinois at Chicago, Department of Neurology, IL.
Stroke. 1994 Dec;25(12):2331-6. doi: 10.1161/01.str.25.12.2331.
The ex vivo effect of aspirin (ASA) on platelet aggregation, the platelet component of thrombosis, was studied at repeated intervals in a cohort of patients taking aspirin for recurrent ischemic stroke prevention to define the maintenance of efficacy over time.
We administered increasing doses of aspirin (from 325 to 1300 mg/d) to patients with previous ischemic stroke and determined the extent of inhibition of platelet aggregation after 2 weeks and thereafter at approximately 6-month intervals.
Over 33 months, 306 patients had platelet aggregation studies performed to define their initial response to ASA therapy. Of these, 228 had complete and 78 had partial inhibition of platelet aggregation at initial testing. To date, 119 of those who had complete inhibition and 52 who had partial inhibition have undergone repeat testing at least once. At repeat testing 39 of the 119 (32.7%) with complete inhibition at initial testing had lost part of the antiplatelet effect of ASA and converted from complete to partial inhibition without change in ASA dosage. Of the 52 with partial inhibition at initial testing, 35 achieved complete inhibition either by ASA dosage escalation (in 325 mg/d increments) or fluctuation of response at the same dosage, but 8 of those 35 (22.8%) had reverted to partial inhibition when tested again. Overall, 8.2% of patients ultimately exhibited ASA resistance to 1300 mg/d-8 of 52 (15.4%) with partial inhibition and 6 of 119 (5.0%) with complete inhibition at initial testing.
The antiplatelet (and presumably the antithrombotic) effect of a fixed dose of ASA is not constant over time in all individuals. The mechanisms by which increased dosage requirement or ASA resistance develops and the clinical significance of this development are currently undefined.
在一组服用阿司匹林预防复发性缺血性卒中的患者中，反复间隔研究阿司匹林（ASA）对血小板聚集（血栓形成的血小板成分）的体外作用，以确定疗效随时间的维持情况。
我们对既往有缺血性卒中的患者给予递增剂量的阿司匹林（从325mg/d增至1300mg/d），并在2周后及此后大约每6个月测定血小板聚集的抑制程度。
在33个月期间，306例患者进行了血小板聚集研究以确定他们对ASA治疗的初始反应。其中，228例在初始检测时血小板聚集完全抑制，78例部分抑制。迄今为止，119例完全抑制和52例部分抑制的患者至少接受了一次重复检测。在重复检测时，初始检测完全抑制的119例患者中有39例（32.7%）失去了部分ASA抗血小板作用，在未改变ASA剂量的情况下从完全抑制转变为部分抑制。初始检测部分抑制的52例患者中，35例通过增加ASA剂量（以325mg/d递增）或在相同剂量下反应波动实现了完全抑制，但这35例中有8例（22.8%）再次检测时又恢复为部分抑制。总体而言，8.2%的患者最终对1300mg/d的ASA表现出抵抗——初始检测部分抑制的52例中有8例（15.4%），完全抑制的119例中有6例（5.0%）。
固定剂量的ASA的抗血小板（可能还有抗血栓形成）作用在所有个体中并非随时间恒定不变。增加剂量需求或ASA抵抗产生的机制以及这种情况的临床意义目前尚不清楚。
