Effect of low-dose aspirin on platelet aggregation inhibition in patients with rheumatoid arthritis

Introduction : The risk for coronary artery disease (CAD) and mortality has increased in patients with rheumatoid arthritis (RA). Aspirin has anti-thrombotic effects and causes reduction in CAD occurrence in high-risk individuals. The objective of present project was evaluating the influence of low-dose aspirin on inhibition of platelet aggregation in patients with RA. Methods: Forty-eight subjects with RA diagnosed based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria and age- and sex-matched healthy participants were studied. All subjects received 81 mg/day aspirin for 10 days. Level of the serum thromboxane B2 (sTxB2), a permanent metabolite of thromboxane A2 (TxA2), was measured before and after therapy using enzyme-linked immunosorbent assay (ELISA) kit. The impotency to decrease sTxB2 production to less than 10 ng/ml indicates suboptimal suppression of platelet aggregation via aspirin. Results: Low-dose aspirin decreased sTxB2 significantly compared with baseline in patients with RA [median interquartile range (IQR): 25.72 (11.78, 90.10) to 7.74 (5.80, 8.82), P < 0.001] and in healthy controls [median (IQR): 40.50 (33.25, 50.90) to 7.30 (4.75, 8.85), P < 0.001]. No remarkable changes were seen in sTxB2 between patients and controls after adjustment (P > 0.050). Pharmacologic influence of aspirin was suboptimal in 6.25% of cases in the presence of higher erythrocyte sedimentation rate (ESR) and in 2.7% of controls. Low-dose aspirin decreased sTxB2 significantly only in patients with Framingham Risk Score (FRS) < 10%. Conclusion: Low-dose aspirin decreased sTxB2 level and suppressed platelet aggregation and therefore, was effective in primary prevention of cardiovascular (CV) events in patients with RA; however, additional studies are required to reach accurate conclusions.

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Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration

Thrombosis Research ◽

10.1016/j.thromres.2008.12.034 ◽

2009 ◽

Vol 124 (1) ◽

pp. 96-100 ◽

Cited By ~ 25

Author(s):

Sofie S. Hedegaard ◽

Anne-Mette Hvas ◽

Erik L. Grove ◽

Jens Refsgaard ◽

Bianca Rocca ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Platelet Aggregation ◽

Low Dose ◽

Stable Coronary Artery Disease ◽

Healthy Individuals ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Artery Disease

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EVALUATION ON EFFECTIVENESS OF LOW DOSE ASPIRIN THERAPY FOR PROTECTION OF THROMBUS FORMATION

10.1055/s-0038-1644817 ◽

1987 ◽

Author(s):

S Kariyone ◽

M Hirakuri ◽

T Yui ◽

T Uchida

Keyword(s):

Platelet Aggregation ◽

Oral Dose ◽

Time Course ◽

Low Dose ◽

Thrombus Formation ◽

Platelet Factor ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Before And After

In order to protect thrombus formation, administration of low dose aspirin has become common. However, its significance for this purpose is still not clear. Effect of small dose of aspirin (ASA) onplatelet aggregation and ability of malondialdehyde(MDA) formation in platelet by the addition of arachidonic acid in vitro were investigated. In clinical study, platelet aggregation, MDA formation of platelet, serum P-thromboglobulin(p-TG), platelet factor 4(PF4) and thromboxane B2(TX-B2) levelswere measured before and after low doseaspirin therapy.Platelet aggregations by ADP, collagen, epinephrin and arachidonate as inducers were significantly suppressed under 12.5 ug/ml ASA in the medium. MDA formation of platelet was remarkably inhibited under 1.6 ug/ml of ASA in the medium in vitro.In patients, single oral dose of 50 mg ASA showed no change on platelet aggregation while the ability of MDA formation decreased 50# of the before. Serum concentration of ASA after oral dose of 50 mg ASA only showed 1.5 to 6.0 ug/ml at maximum.Daily dose of 50 mg ASA was continued during 10 days. Changes of various factors due to the time course were observed. Inhibitions of platelet aggregation were seen from 5th day on ADP and collagenand from 2nd day on epinephrin and arachidonate as inducers during the therapy. MDA formations of platelet were decreased quickly and it became almost zero at 5th day. ASA levels in the patient serum reached plateau as 8 or 9 ug/ml from 3rdday.Various patients with a possibility of thrombus formation were administered daily 50 mg ASA during 10 days. Platelet aggregations and MDA production, serum β-TG, PF4 and TXB2 levels were measured before and after the therapy. Platelet aggregations by ADP, collagen and epinephrin as inducers were significantly suppressed after the therapyand MDA production of platelet was also markedly decreased after the therapy. There were no significant changes in serumβ-TG and PF4 levels while TXB2 level tended to decrease after the therapy.From these results, it was concluded that daily 50 mg ASA oral dose was certainly effective for protection of thrombus formation.

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Increased prostacyclin production during exercise in untrained and trained men: effect of low-dose aspirin

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.5.1832 ◽

1995 ◽

Vol 78 (5) ◽

pp. 1832-1838 ◽

Cited By ~ 19

Author(s):

R. H. Boger ◽

S. M. Bode-Boger ◽

E. P. Schroder ◽

D. Tsikas ◽

J. C. Frolich

Keyword(s):

Platelet Aggregation ◽

Prostaglandin E2 ◽

Low Dose ◽

Submaximal Exercise ◽

Trained Subjects ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Before And After ◽

Excretion Rates ◽

Prostacyclin Production

The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor-6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2 excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After low-dose aspirin administration, the selective stimulatory effect of submaximal exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor-TxB2 was increased by exercise; this effect was significantly enhanced by low-dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of submaximal exercise on prostacyclin production is mostly due to an activation of prostacyclin synthesis from endogenous precursors rather than the result of an enhanced endoperoxide shift from activated platelets to the endothelium. This effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day of aspirin do not impair exercise-induced endothelial prostacyclin production.

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24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease

Thrombosis and Haemostasis ◽

10.1160/th10-02-0082 ◽

2011 ◽

Vol 105 (02) ◽

pp. 336-344 ◽

Cited By ~ 98

Author(s):

Adeline Vermillet ◽

Bernadette Boval ◽

Carine Guyetand ◽

Thibaut Petroni ◽

Jean-Guillaume Dillinger ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Platelet Aggregation ◽

Low Dose ◽

Once Daily ◽

Biological Efficacy ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Artery Disease ◽

Aspirin Ingestion

SummaryAspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h –24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h – 4% of patients, 6 h – 4%, 12 h – 11%, 16 h – 16%, 20 h – 19% and 24 h – 28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75–100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance» at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.

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Chronic ischaemic heart disease and rivaroxaban: which patients derive the greatest benefit?

European Heart Journal Supplements ◽

10.1093/eurheartj/suaa128 ◽

2020 ◽

Vol 22 (Supplement_L) ◽

pp. L24-L27

Author(s):

Leonardo Bolognese ◽

Massimo Felici

Keyword(s):

Low Dose ◽

Stable Coronary Artery Disease ◽

Composite Endpoint ◽

Platelet Inhibition ◽

Everyday Clinical Practice ◽

Major Cardiovascular Events ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Artery Disease ◽

Cv Disease

Abstract Patients with established cardiovascular (CV) disease may suffer further CV events, despite receiving optimal medical treatment. Although platelet inhibition plays a central role in the prevention of new events, the use of anticoagulant therapies to reduce events in atheromatous disease has, until recently, been overlooked. The recent Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial showed that rivaroxaban 2.5 mg twice daily given with low-dose aspirin reduces the incidence of the composite endpoint of stroke, heart attack, and death in patients with stable coronary artery disease. Although there are some limitations to the study, COMPASS offers promising conclusions and may change secondary prevention in patients with stable CV disease. This article reviews the results of the COMPASS study and how these results may affect patient management in everyday clinical practice.

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Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease

Annals of Emergency Medicine ◽

10.1016/s0196-0644(05)81237-5 ◽

1991 ◽

Vol 20 (2) ◽

pp. 213-214

Author(s):

Cindy Madden

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Low Dose ◽

Unstable Coronary Artery Disease ◽

Dose Aspirin ◽

Intravenous Heparin ◽

Low Dose Aspirin ◽

Artery Disease

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Reproducibility, Pre-Analytical Variables and Effect of Aspirin On Soluble P Selectin and CD40 Ligand.

Blood ◽

10.1182/blood.v120.21.2255.2255 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2255-2255

Author(s):

Vanessa Valdes ◽

Michael A. Nardi ◽

Jeffrey S Berger

Keyword(s):

Low Dose ◽

Conflicts Of Interest ◽

Cd40 Ligand ◽

Rank Test ◽

Enzyme Linked Immunosorbent Assay ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Soluble Cd40l ◽

Soluble P ◽

Over Time

Abstract Abstract 2255 Background: Several studies have demonstrated a significant association between platelet plasma markers (soluble CD40 ligand [sCD40L] and soluble p selectin [sPselectin]) and in-vivo platelet activation and cardiovascular events. However, the reliability and pre-analytical variation of these assays remain uncertain. We therefore sought to investigate the reproducibility of these assays, type of collection (plasma or sera), correlation between sCD40L and sPselectin, and the effect of aspirin. Methods: Following an overnight fast, 40 healthy volunteers had early morning phlebotomy during 4 consecutive weeks. Subjects took aspirin 81mg daily x7 days between weeks 3 and 4. Platelet poor plasma was obtained via centrifugation at 2500 × g for ten minutes within 15 minutes of phlebotomy while serum samples were similarly processed at 30 minutes after phlebotomy. Samples were aliquoted and stored at −80°C no more than five minutes after completion of centrifugation. Concentrations of sPselectin and sCD40L were determined in plasma and serum by quantitative enzyme linked immunosorbent assay (Bender MedSystems: BMS219 & BMS293, respectively). Reproducibility over time of levels of sPselectin and sCD40L was assessed by coefficient of variation (CV). Correlation was assessed using Pearson r statistic. The difference between levels pre and post aspirin was measured with Wilcoxon Signed- Rank test. Data is presented as median [interquartile range]. Results: Soluble CD40L measurements were reproducible over time in plasma (Week 1: 0.72 ng/mL [0.35–1.63], Week 2: 0.72 [0.36–1.69], Week 3: 0.66 [0.34– 1.7]; CV: 9.6 %) and serum (Week 1: 2.43 [2.12– 2.99], Week 2: 2.26 [1.8– 2.98], Week 3: 2.44 [1.75– 3.05]; CV 8%). Soluble P-selectin measurements were also reproducible over time in plasma (Week 1: 58.9 ng/mL [46.2–70.8], Week 2: 55.5 [45.4–68.6], Week 3: 52.6 [43.8–62.8]; CV: 9.4%) and serum (Week 1: 116 ng/mL [94.6–145.5], Week 2: 113.6 [90.7–149.6], Week 3: 111.9 [94.1–148.8]; CV: 6%). Measurement of sCD40L in plasma correlated with levels in serum before aspirin (r=0.88, p< 0.0001) and after aspirin (r=0.87, p< 0.0001) as did levels of sPselectin in plasma correlate with levels in serum before aspirin (r=0.66, p< 0.0001) and after aspirin (r=0.54, p= 0.0004). There was no significant correlation between sCD40L and sPselectin before (r=-0.06, p=0.704) or after aspirin (r=-0.0956, p=0.573) in plasma or in sera (before aspirin, (r= 0.03, p=0.853) or after aspirin (r=0.11, p=0.482)). After 1-week of aspirin 81mg/day, there was a reduction in sCD40L in serum (2.43 ng/mL vs. 2.07; p<0.0001) and plasma (0.72 ng/mL vs. 0.64; p=0.245), however, the latter was not statistically significant. There was a significant reduction in sPselectin following a week of low-dose aspirin in both serum (116 ng/mL vs. 107.1; p<.0001) and plasma (58.9 ng/mL vs. 51; p=0.019). Conclusions: Soluble CD40L and sPselectin are independent markers that are reproducible in both plasma and sera (CV <10% for every comparison) when performed in a laboratory with standardized methodology. One week of low-dose aspirin (81mg/day) effectively reduces sPselectin and sCD40L. Disclosures: No relevant conflicts of interest to declare.

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