Low-dose aspirin inhibits thromboxane, but not prostacyclin, production by human placental arteries

This study vas undertaken to determine if there was a dose of oral aspirin that would inhibit platelet cyclooxygenase but that had no effect on venous cyclo-oxygenase. Varicose veins were surgically removed from 68 patients of whom 21 had taken no medicines pre-operatively. Three groups of patients took aspirin 300 mg 14 hours (n=10), 24 hours (n=10) and 48 hours (n=9) pre-operatively. Two other groups took 40.5 mg (n=9) and 81 mg (n=9) 14 hours preoperatively. Two 6 mm discs of venous tissue were incubated with plasma that contained 1 mM sodium arachidonate (NaAA) and the anti-aggregatory activity of the plasma was compared with that of synthetic PGI2 in aspirinised citrated PRP challenged with ADP. PGI2 production in this procedure was confirmed by specific radio-immunoassay for 6-keto PGF1α. All doses of aspirin except 40.5 mg markedly inhibited PGI2 synthesis. Little recovery was seen with 300 mg at 48 hour post-drug.Five normal volunteers took aspirin 300 mg and 5 others 40.5 mg. Citrated PRP was prepared immediately before, 2, 24, 48, 96 and 192 hours after ingesting the drug. The amount of malondialdehyde (MDA, a marker for thromboxane synthesis) that was produced when 1 mM NaAA was added, was markedly reduced compared to the control at 2 and 24 hours by both 40.5 mg and 300 mg and thereafter it returned slowly to control values. This study indicates that 40.5 mg of aspirin inhibits platelet cyclo-oxygenase but not vessel wall cyclo-oxygenase.

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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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The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta

International Journal of Molecular Sciences ◽

10.3390/ijms22136985 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6985

Author(s):

Scott W. Walsh ◽

Jerome F. Strauss

Keyword(s):

Low Dose ◽

Meta Analysis ◽

Aspirin Therapy ◽

Specific Expression ◽

The Road ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Protease Activated Receptor 1 ◽

Hydroxyeicosatetraenoic Acids ◽

Prostacyclin Production

The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started <16 weeks of gestation and at doses >100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin’s effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.

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Esomeprazole Lessened Ulcer Risk For Patients on Low-Dose Aspirin

Internal Medicine News ◽

10.1016/s1097-8690(06)73895-1 ◽

2006 ◽

Vol 39 (14) ◽

pp. 52

Author(s):

Doug Brunk

Keyword(s):

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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Alert Issued on Low-Dose Aspirin + Ibuprofen

Clinical Psychiatry News ◽

10.1016/s0270-6644(06)71782-9 ◽

2006 ◽

Vol 34 (10) ◽

pp. 8

Author(s):

ELIZABETH MECHCATIE

Keyword(s):

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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Benefits of Low-Dose Aspirin Alone Offset Costs

Family Practice News ◽

10.1016/s0300-7073(07)71179-9 ◽

2007 ◽

Vol 37 (19) ◽

pp. 11

Author(s):

KERRI WACHTER

Keyword(s):

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651063 ◽

1987 ◽

Vol 57 (01) ◽

pp. 062-066 ◽

Cited By ~ 36

Author(s):

P A Kyrle ◽

J Westwick ◽

M F Scully ◽

V V Kakkar ◽

G P Lewis

Keyword(s):

Platelet Activation ◽

Thrombin Generation ◽

Low Dose ◽

Bleeding Time ◽

Blood Platelets ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Plug Formation ◽

Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

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Increased Thromboxane Biosynthesis in Essential Thrombocythemia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649916 ◽

1995 ◽

Vol 74 (05) ◽

pp. 1225-1230 ◽

Cited By ~ 71

Author(s):

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Raffaele Tartaglione ◽

Sergio Cortelazzo ◽

Tiziano Barbui ◽

...

Keyword(s):

Platelet Count ◽

Platelet Activation ◽

Essential Thrombocythemia ◽

Therapeutic Strategy ◽

Low Dose ◽

Thrombotic Risk ◽

Dose Aspirin ◽

Gender And Age ◽

Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

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