Ibudilast, a Phosphodiesterase Inhibitor, in Combination with Low-dose Aspirin Potently Inhibits Guinea Pig Carotid Artery Thrombosis without Extending Bleeding Time and Causing Gastric Mucosal Injury

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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Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.2019.1672781 ◽

2019 ◽

Vol 54 (10) ◽

pp. 1199-1204

Author(s):

Taned Chitapanarux ◽

Nirush Lertprasertsuke ◽

Acharaporn Kongnak

Keyword(s):

Helicobacter Pylori ◽

Low Dose ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Dose Aspirin ◽

Low Dose Aspirin

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Bleeding time prolonged by daily low-dose aspirin is shortened by one medium dose aspirin

Acta Anaesthesiologica Scandinavica ◽

10.1111/j.1399-6576.2008.01766.x ◽

2008 ◽

Vol 52 (9) ◽

pp. 1226-1230 ◽

Cited By ~ 3

Author(s):

T. YOKOYAMA ◽

F. YAMASAKI ◽

K. YAMASHITA ◽

M. MANABE ◽

K. SUWA

Keyword(s):

Low Dose ◽

Bleeding Time ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Medium Dose

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Preventive Effects of Lansoprazole and Famotidine on Gastric Mucosal Injury Induced by Low-Dose Aspirin inHelicobacter pylori-Negative Healthy Volunteers

The Journal of Clinical Pharmacology ◽

10.1177/0091270010376194 ◽

2011 ◽

Vol 51 (7) ◽

pp. 1079-1086 ◽

Cited By ~ 16

Author(s):

Masafumi Nishino ◽

Mitsushige Sugimoto ◽

Chise Kodaira ◽

Mihoko Yamade ◽

Takahiro Uotani ◽

...

Keyword(s):

Healthy Volunteers ◽

Low Dose ◽

Mucosal Injury ◽

Gastric Mucosal Injury ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Preventive Effects

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Geographic differences in low-dose aspirin-associated gastroduodenal mucosal injury

World Journal of Gastroenterology ◽

10.3748/wjg.v21.i25.7709 ◽

2015 ◽

Vol 21 (25) ◽

pp. 7709 ◽

Cited By ~ 7

Author(s):

Katsunori Iijima

Keyword(s):

Low Dose ◽

Mucosal Injury ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Geographic Differences

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M1923 Esophageal Mucosal Injury with Low-Dose Aspirin and Its Prevention By Rabeprazole

Gastroenterology ◽

10.1016/s0016-5085(09)62058-8 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-447

Author(s):

Mitsushige Sugimoto ◽

Masafumi Nishino ◽

Chise Kodaira ◽

Mihoko Yamade ◽

Mutsuhiro Ikuma ◽

...

Keyword(s):

Low Dose ◽

Mucosal Injury ◽

Dose Aspirin ◽

Low Dose Aspirin

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Upper Gastrointestinal Mucosal Injury and Symptoms in Elderly Low-Dose Aspirin Users

Gastroenterology Research and Practice ◽

10.1155/2015/252963 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Yuji Shimada ◽

Akihito Nagahara ◽

Mariko Hojo ◽

Daisuke Asaoka ◽

Hitoshi Sasaki ◽

...

Keyword(s):

Mental Component Summary ◽

Gastrointestinal Endoscopy ◽

Low Dose ◽

Clinical Information ◽

Mucosal Injury ◽

Upper Gastrointestinal Endoscopy ◽

Frequency Scale ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Upper Gastrointestinal

Background. We investigated the prevalence, symptoms, and QOL impact of esophageal (EI), gastric (GI), and duodenal mucosal injury (DI) individually between low-dose aspirin (LDA) users and nonusers to reveal the clinical features of LDA-related mucosal injury.Methods. Data were extracted from the records of subjects who underwent upper gastrointestinal endoscopy at our department between April 2008 and December 2013. Responses from 3162 elderly patients on Frequency Scale for Symptoms of GERD (FSSG) and SF-8 QOL questionnaires (SF-8) were analyzed. FSSG items were classified into total score (TS), reflux score (RS), and dyspepsia score (DS). The SF-8 questionnaire consisted of the physical component summary (PCS) and mental component summary (MCS).Results. Prevalence among LDA users and nonusers, respectively, was 9.6% and 10.0% (P=0.83) for EI, 35.9% and 27.5% (P=0.0027) for GI, 3.3% and 3.4% (P=0.84) for DI, and 8.2% and 5.2% (P=0.036) for mucosal injury in 2 or more organs. LDA users diagnosed with EI had significantly lower PCS, LDA users diagnosed with GI had significantly lower DS, and LDA users diagnosed with DI had significantly lower RS and significantly lower MCS.Conclusion. These results provide important clinical information indicating that symptom-based management is not appropriate in LDA users regarding upper gastrointestinal mucosal injury.

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PROSTACYCLIN AND THROMBOXANE A2 GENERATION IN VIVO IN MAN -EFFECT OF LOW DOSE ASPIRIN

10.1055/s-0038-1643371 ◽

1987 ◽

Author(s):

P A Kyrle ◽

H G Eichler ◽

K Lechner

Keyword(s):

Vessel Wall ◽

Low Dose ◽

Bleeding Time ◽

Thromboxane A2 ◽

Significant Inhibition ◽

Prostaglandin Metabolism ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Wall Interaction

The effect of a low-dose aspirin regimen on platelet and vascular prostaglandin metabolism was studied in vivo in man. In a double-blind placebo-controlled cross-over study, 7 healthy male volunteers were treated with aspirin (35 mg.day−1 or placebo for 7 days. After a washout period of 2 weeks, the subject were crossed to the alternate treatment. 12 hours after the last dose of aspirin or placebo formation of thromboxane A2 (TxA2) and prostacyclin (FGI2) was measured in blood emerging from a standardized injury of the microvasculature made to determine bleeding time. TxA2 and PGI2 were measured as their stable degradation products, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto PGF1α), using radioimmunoassay procedures. When subjects were treated with placebo, there was a rapid and substantial generation of both TxA2 and PGI2 at the site of plate-let-vessel wall interaction. This was reflected by an increase of TxB2 from 2.8±1 ng/ml and of 6-keto-PGF1α from 38.6±14.6pg/ml in the first minute to 4.5±0.6 ng/ml TxB2 and 154±50 pg/ml 6-keto-PGF1α after 4 minutes. Low-dose aspirin caused a significant inhibition of both TxA2 and PGI2 generation in bleeding time blood as represented by 65-92% and 81-84% inhibition of TxB2 and 6-keto-PGF1α Respectively throughout the 4 minute study period. We conclude that (a) rapid activation of both platelet prostaglandin metabolism and vascular PGI2 biosynthesis occurs at the site of platelet-vessel wall interaction and (b) low-dose aspirin results in a significant inhibition of platelet and vascular cyclo-oxygenase activity. Thus, our data fail to confirm the concept of a differential effect of low-dose aspirin on platelet and vascular prostaglandin synthesis in vivo in man.

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