Aspirin response and failure in cerebral infarction.

Abstract

Background and Purpose: The purpose of this study was to assess the biological effect of aspirin as measured by the inhibition of platelet aggregation in patients taking aspirin for stroke prevention and in patients with acute stroke.Methods: We administered increasing doses of aspirin (325, 650, 975, and 1,300 mg daily) to 113 patients for stroke prevention and measured the inhibition of platelet aggregation in these patients and in 33 patients with acute stroke taking aspirin before stroke onset.Results: Eighty-five patients on <325 and six on .650 mg aspirin daily had complete inhibition of platelet aggregation. Increase of the dose by 325 mg in nine of the 22 patients with partial inhibition of platelet aggregation produced complete inhibition in five patients at 650 mg and in one at 975 mg. At 1,300 mg, three patients still had only partial inhibition of platelet aggregation (aspirin resistance). Of the 33 inpatients with acute stroke, 24 had platelet aggregation studies done before further administration of aspirin. Of these, 19 had complete inhibition of platelet aggregation and three had partial inhibition, with production of complete inhibition of platelet aggregation at dose escalation; one patient was aspirinresistant and the other noncompliant.Conclusions: How the inhibition of platelet aggregation relates to stroke prevention remains unclear. The ability of aspirin and the dose required to inhibit platelet aggregation may depend upon the individual. (Stroke 1993;24:345-350)

Comparative antiplatelet activity of COX1 NSAIDS versus aspirin, encompassing regimen simplification and gastroprotection: a call for a controlled study

“…It also represents a simpler regimen than taking misoprostol three times a day and waiting 20 minutes to subsequently take an NSAID or aspirin dose. Lack of efficacy of aspirin on collagen and arachidonic acid-induced platelet aggregation and inadequate response in 14% of aspirin-treated individuals is bothersome, but routinely observed (4,5,28,30). Absence of aspirin dose response in the current study mirrors previous reports (28,31).…”

“…Blood was drawn 14-18 hours after the last NSAID or aspirin dose with a butterfly needle and multiple syringes and immediately placed into plastic tubes containing citrate anticoagulant (nine parts blood to one part anticoagulant) and mixed. Platelet rich plasma and platelet poor plasma were prepared by standardization with platelet count adjusted to 350,000 (28). Aliquots were incubated at 37 degrees for one minute before addition of aggregating agent: 500 µM arachidonic acid, 5 µM adenosine diphosphate, 0.8 µg/ml collagen.…”

“…Aggregation was monitored for 8 minutes at 37 degrees with 1,000 rpm stirring following aggregating agent addition. Platelet function was considered adequately suppressed if either ADP-induced platelet aggregation was reduced 80% from baseline, collagen-induced aggregation was reduced 90% or arachidonic acid induced aggregation was completely inhibited after one week of NSAID or aspirin therapy (1,28). Individuals with inadequate response to NSAID (5 individuals) had repeat testing one week after initiation of 325 mg daily aspirin doses.…”

Aspirin resistance in vitro and hypertension in stroke patients

“…Despite its large use, there are concerns about the efficacy of aspirin and methods to evaluate it [2,3]. Indeed, it appears that the antiplatelet effect of aspirin is not uniform in all patients and previous studies estimated that 8-45% of the population were aspirin resistant [4][5][6][7][8]. Most studies have focused on patients with coronary artery disease, although a few reports have identified aspirin resistance in patients with stroke or cerebrovascular disease [6][7][8][9].…”

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)

“…Certain individuals or groups of individuals, e.g. diabetics or stroke survivors (11)(12)(13), may not receive the full benefit of aspirin, although defining, measuring, and assessing such resistance to the therapeutic effects of aspirin are complex and incomplete (14 -17). A single low dose of coated enteric aspirin fails to inhibit platelet function in half of those studied, reflecting varied bioavailability that is not genetically encoded (18).…”