Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease.

The purpose of our study was to investigate the effects of different doses of acetylsalicylic acid on platelet aggregation. Among inpatients of the National Taiwan University Hospital, 236 cases of completed stroke and seven cases of reversible ischemic neurologic deficit that were diagnosed by computed tomography of the brain and that had not ingested acetylsalicylic acid or acetylsalicylic acidlike drugs for > 2 weeks before admission were selected for this study. Thromboxane B 2 and 6-keto-PGF lo were measured by radioimmunoassay, threshold concentration of adenosine diphosphate was measured by Born's method, and circulating platelet aggregates were measured by the method of Wu and Hoak. Various single doses of acetylsalicylic acid (75, 300, or 600 mg) or 300 mg acetylsalicylic acid every 6 hours for four doses or one dose of 300 mg acetylsalicylic acid with 75 mg dipyridamole significantly suppressed the mean plasma thromboxane B, concentrations and elevated the mean adenosine diphosphate threshold concentrations. Abnormal plasma thromboxane B, concentrations, adenosine diphosphate threshold concentrations, or circulating platelet aggregate ratios were significantly normalized after administration of these regimens. The effects were not significantly different among treatment groups. Forty milligrams of acetylsalicylic acid seemed to have less platelet-inhibitory effect. A single dose of 75 mg acetylsalicylic acid significantly inhibited platelet hyperfunction and effectively corrected the abnormal plasma thromboxane B 2 concentrations, adenosine diphosphate threshold concentrations, and circulating platelet aggregate ratios. Higher doses did not enhance the inhibitory effect. In addition, this single dose of acetylsalicylic acid did not significantly suppress plasma 6-keto-PGF lo . We conclude that 75 mg acetylsalicylic acid per day is adequate to inhibit platelet hyperfunction. (Stroke 1988; 19:566-570) I t has been documented that acetylsalicylic acid (ASA) has an inhibitory effect on platelet function through specific blocking of the enzyme cyclooxygenase 1 ; thus, this antiplatelet agent is now widely used for the prevention of ischemic cerebrovascular disease.Treatment with oral administration of 1,000-1,300 mg ASA/day has been reported to have a significantly beneficial effect in male patients with threatened stroke, 2 in patients with a history of multiple transient ischemic attacks (TIAs), 3 and in the secondary prevention of atherothrombotic cerebral infarction 4 or to have no favorable influence in patients with reversible cerebral ischemic attacks. 5 However, an increasing number of studies have documented that high doses of ASA might depress not only thromboxane A 2 (TXA 2 ) but also prostacyclin (PGIJ.6 " 10 Since PGI 2 has an inhibitory effect on platelet activity, suppression of this prostaglandin could possibly have adverse effects on Address for correspondence: Dr. Ti-Kai Lee, Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China...

Section: Discussionmentioning

confidence: 98%

Inhibitory effect of acetylsalicylic acid on platelet function in patients with completed stroke or reversible ischemic neurologic deficit.

Lee

Chen

Lien

et al. 1988

“…However, it has been reported that this functional activation is not directly connected with the occurrence of thrombosis; there are actually cases where activated platelets are consumed by cerebral thrombosis and the level of aggregability is reduced, 20 and there is no consistent correlation between bleeding time or thromboxane B2 levels and platelet aggregability. 21 - 22 In addition, thromboxane B 2 determination is not a direct measurement of platelet aggregation. The changes in platelet aggregability may also depend on the individual or the methods used.…”

Section: Establishment Of the Appropriate Conditions For The Plateletmentioning

confidence: 99%

Compliance with antiplatelet therapy in patients with ischemic cerebrovascular disease. Assessment by platelet aggregation testing.

Komiya

Kudo

Urabe

et al. 1994

Background and Purpose Antiplatelet therapy is currently one of the methods for preventing transient ischemic attacks and cerebral thrombosis. Because antiplatelet agents are generally administered on a long-term basis, patient compliance is an important factor. The purpose of this study was to determine the compliance of patients during antiplatelet therapy by testing platelet aggregation.Methods To establish the conditions for measuring platelet aggregation, the platelet aggregation test was performed in patients taking 81 mg/d aspirin or 200 mg/d ticlopidine at the following final concentrations of aggregation-inducing agents: 0.5, 1, 2, and 4 yitmol/L ADP and 0.5 and 2 jug/mL collagen. The optimum measurement conditions for assessing patient compliance were determined. Under the conditions determined in the first study, platelet aggregation was assessed, and the effects of treatment were studied in 159 outpatients and 79

“…In each patient, platelet aggregation after stimulation with sodium arachidonate 18 was measured using a Born aggregometer twice during the first 2 months after the start of the study medication and again at each subsequent follow-up visit. If platelet inhibition was <80%, it was measured again 1 week later and the aspirin dose was increased in 10-mg increments until satisfactory inhibition had been obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Theoretically, a lower dose might even be more effective than a high dose. With very low doses, production of prostacyclin in the vessel wall may be partially preserved, clin in cerebrovascular disease are still limited, 14 -17 its documented ability to reduce platelet aggregation 18 might be important to preserve. The inhibition of platelet cyclooxygenase requires a very low dose of aspirin, which results in near-cessation of thromboxane production, inhibition of platelet aggregation, 19 - 20 and increase of bleeding time.…”

mentioning

confidence: 99%

“…The inhibition of platelet cyclooxygenase requires a very low dose of aspirin, which results in near-cessation of thromboxane production, inhibition of platelet aggregation, 19 - 20 and increase of bleeding time. 18 Such considerations formed the background for our present trial in which we examined the prophylactic effect of very-low-dose aspirin individually titrated to prevent in vitro platelet aggregation in patients having undergone carotid endarterectomy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Danish very-low-dose aspirin after carotid endarterectomy trial.

Boysen

Sørensen

Juhler

et al. 1988

Self Cite

The effect of very-low-dose aspirin as an antithrombotic agent was evaluated blindly in 301 patients who had recently undergone carotid endarterectomy. After randomization, 150 patients received aspirin and 151 received placebo. The two groups were comparable with regard to age, sex, blood pressure, previous cerebrovascular events, and smoking habits. The effect of the study medication on platelet aggregation was measured twice in each patient during the first 2 months and at each follow-up visit; the dose was individually adjusted. In 76% of the patients receiving aspirin, 50 mg/day gave satisfactory platelet inhibition, 13% needed 60 mg/ day, 8% needed 70 mg/day, and 3% needed 100 mg/day. Platelet aggregation was found to be inhibited in only 1.2% of the measurements in the patients receiving placebo. Observation during treatment averaged 21 months; total intention-to-treat follow-up averaged 25 months. For the combined outcome events of transient ischemic attack, stroke, acute myocardial infarction, and vascular death, aspirin reduced risk by 11% (95% confidence limits: -38% to 48%,/>>0.1). Thus, there was no significant effect of very-low-dose aspirin in our trial.