Dosage frequency for suppression of platelet function by low dose aspirin therapy

doi:10.1016/0049-3848(82)90283-3

Thrombosis Research

Volume 27, Issue 1, 1 July 1982, Pages 99-110

https://doi.org/10.1016/0049-3848(82)90283-3 Get rights and content

Abstract

A study of platelet aggregation and MDA production after an oral dose of 300 mg aspirin indicated that partial recovery of platelet function occurred when approximately one third of the circulating platelets had been replaced by new (uninhibited) platelets. In vitro studies on mixtures of normal and aspirin inhibited platelets indicated partial restoration of platelet aggregation and thromboxane B₂ production with as little as 10% of normal platelets in some subjects. Restoration of full function required a higher proportion of normal platelets. There was considerable variation between subjects. These data suggest that complete suppression of platelet functions in all normal subjects requires daily administration of the drug.

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Citation Excerpt :
O'Brien36 demonstrated that abnormal platelet aggregation after ingestion of ASA can be corrected ex vivo by 10% normal platelet-rich plasma. Furthermore, it has been reported that if as little as 20% of platelets have normal COX-1 activity, hemostasis is unimpaired.37,38 Therefore, stopping ASA for 72 hours is likely to ensure substantial (if not complete) recovery of platelet function.
Worldwide, 200 million adults undergo major noncardiac surgery annually, and 10 million of these patients will have a major vascular complication. Low-dose clonidine and low-dose acetyl-salicylic acid (ASA) may prevent major perioperative vascular complications. We therefore initiated the POISE-2 trial to establish the perioperative effects of these 2 interventions.
The POISE-2 trial is a 2 × 2 factorial randomized controlled trial of low-dose ASA vs placebo and low-dose clonidine vs placebo in 10,000 patients at risk for a perioperative cardiovascular event who are undergoing noncardiac surgery. Both study drugs are initiated prior to surgery (goal 2-4 hours) and are continued after surgery. Patients, health care providers, data collectors, and outcome adjudicators are blinded to treatment allocation. The primary outcome is a composite of mortality and nonfatal myocardial infarction at 30 days after randomization.
To date, the POISE-2 trial has recruited more than 9,000 patients from 135 centers in 23 countries. Among the first 7,500 patients recruited, patients' mean age was 68.2 years, 53.4% were male, 34.0% had a history of vascular disease, and 38.3% had diabetes that was treated. Participants had orthopedic (38.1%), general (27.0%), urologic or gynecologic (17.2%), vascular (6.6%), thoracic (5.7%), and other (5.4%) surgery.
POISE-2 is a large international trial that will rigorously evaluate the effects of low-dose clonidine and ASA in patients having noncardiac surgery.
Influence of antiplatelet therapy on postoperative recurrence of chronic subdural hematoma: A multicenter retrospective study in 719 patients
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Even if only 20% of the total platelet population has normal cyclooxygenase activity, normal platelet aggregation is maintained. Furukawa et al. reported platelet aggregation to be extremely enhanced one day after discontinuing oral aspirin and that the normal range was restored 3 days after discontinuation [26,27]. This is consistent with our present results.
The present study tested the hypothesis of whether antiplatelet agents (APA) induce chronic subdural hematoma (CSDH) recurrence via a platelet aggregation inhibitory effect.
We examined risk factors for CSDH recurrence, focusing on APA, in 719 consecutive patients who admitted to three tertiary hospitals and underwent burr-hole craniostomy and irrigation for CSDH. This was a multicenter, retrospective, observational study.
Age, sex, history of diabetes mellitus, hypertension, chronic renal failure, alcohol consumption habits, consciousness disturbance on admission, or preoperative CT density was not associated with recurrence. Subdural drainage was significantly associated with less recurrence. Preoperative oral APA administration was significantly associated with more recurrence. The recurrence rate of CSDH in non-APA group was 11% if surgery was performed on admission. However, if surgery was performed immediately after discontinuation of oral APA administration, the recurrence rate in APA group significantly increased to 32% (p value < 0.0001; odds ratio, 3.77; 95% confidence interval, 1.72–8.28). The effect of APA on CSDH recurrence gradually diminished as the number of days until initial surgery, after stopping APA, increased.
Antiplatelet therapy significantly influences the recurrence of CSDH.
Aspirin
2007, Platelets
Aspirin
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Changes in platelet aggregation after suspension of aspirin therapy
2004, Journal of Thoracic and Cardiovascular Surgery
Aspirin in patients undergoing noncardiac surgery
2014, New England Journal of Medicine
Citation Excerpt :
Because we did not randomly assign patients according to the timing of aspirin cessation before surgery, we cannot determine the most effective timing to minimize bleeding risk. Studies have suggested that hemostasis is unimpaired if at least 20% of the platelets have normal COX-1 activity25,26 and 12% of circulating platelets are replaced every 24 hours.27,28 Therefore, stopping aspirin 72 or more hours before surgery may be adequate to minimize the risk of perioperative bleeding.
There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not.
Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.
Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.)
In this trial, administering aspirin before surgery and during the early postsurgical period did not affect the rate of death or nonfatal MI but increased the risk of major bleeding. This was true in patients who had not been taking aspirin and in those on a long-term aspirin regimen.
Myocardial infarction is the most common major vascular complication that occurs after noncardiac surgery.1, 2, 3 Noncardiac surgery is associated with platelet activation,⁴ and coronary-artery thrombus may be a mechanism of perioperative myocardial infarction.⁵,⁶ Aspirin inhibits platelet aggregation,⁷ and the perioperative administration of aspirin may prevent major vascular complications by inhibiting thrombus formation.⁸
In a meta-analysis of data from large, randomized trials involving more than 110,000 patients who were not undergoing surgery, the use of aspirin was shown to prevent myocardial infarction and major vascular events.⁹ High-dose aspirin has not been shown to be superior to low-dose aspirin in preventing . . .

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PaperDosage frequency for suppression of platelet function by low dose aspirin therapy

Abstract

Thrombosis Research

Lancet

Thrombos. Res.

Biochem. Biophys. Res. Commun.

Thrombosis Res.

Thrombosis Research

Thrombosis Research

Theombosis Research

Blood

Lancet

Lancet

Editorial

Registry of prospective clinical trials

Aspirin and thombo-embolism: A possible dilemna

New Engl. J. Med.

Platelet aggregability, thromboxane A2 and malonaldehyde formation following administration of aspirin to man

Thrombos. Research

Secondary prevention of myocardial infarction - the present state of the Art

Brit. Med. J.

Thrombogenic effect of high dose aspirin rabbits

Acetylation of prostaglandin synthetase by aspirin

Paper
Dosage frequency for suppression of platelet function by low dose aspirin therapy

Platelet aggregability, thromboxane A₂ and malonaldehyde formation following administration of aspirin to man