Inhibition of Adenosine Diphosphate-Induced Secondary Aggregation and Other Platelet Functions by Acetylsalicylic Acid Ingestion

Zucker, Marjorie B.; Peterson, Jane A.

doi:10.3181/00379727-127-32737

Cited by 311 publications

(110 citation statements)

References 4 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…However, a somewhat greater initial slope as well as an increased reversibility were seen in the presence of aspirin (Fig. 3), suggesting stimulation of the first phase and inhibition of the second phase of aggregation (8).…”

Section: Resultsmentioning

confidence: 99%

“…Our findings that PGG2 and/or PGH2 are formed during thrombin-induced aggregation and that they are powerful aggregating agents indicate that they play a role in platelet aggregation. Aspirin, an inhibitor of prostaglandin biosynthesis in platelets (16), has been reported to inhibit the second phase of platelet aggregation (8). It is suggested that this effect is due to inhibited formation of PGG2 and PGH2 from arachidonic acid within the platelet.…”

Section: E25mentioning

confidence: 99%

See 1 more Smart Citation

Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation

Hámberg

Svensson

Wakabayashi

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

848

290

View full text Add to dashboard Cite

Incubation for a short time of arachidonic acid with the microsomal fraction of a homogenate of the vesicular gland of sheep in the presence of 1 mM p-mercuribenzoate followed by extraction and silicic acid chromatography yielded two prostaglandin endoperoxides. The structures of these compounds, i.e., 15-hydroperoxy-9a,11a-peroxidoprosta-5,13-dienoic acid (prostaglandin G2) and 15-hydroxy-9a,lla-peroxidoprosta-5,13-dienoic acid (prostaglandin H2), were assigned mainly by a number of chemical transformations into previously known prostaglandins. The new prostaglandins were 50-200 times (prostaglandin G2) and 100-450 times (prostaglandin H2) more active than prostaglandin E2 on the superfused aorta strip. The half-life of the prostaglandin endoperoxides in aqueous medium (about 5 min) was significantly longer than that of "rabbit aorta-contracting substance" released from guinea pig lung, indicating that none of the prostaglandin endoperoxides is identical with this factor. Addition of 10-300 ng/ml of the endoperoxides to suspensions of washed human platelets resulted in rapid aggregation. Furthermore, platelet aggregation induced by thrombin was accompanied by release of material reducible by stannous chloride into prostaglandin F2a, thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: E25mentioning

confidence: 99%

Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation

Hámberg

Svensson

Wakabayashi

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

848

290

View full text Add to dashboard Cite

show abstract

“…42 Similarly a decrease in fibrinolysis induced by both cellular and plasmatic factors after ingestion of 1 g of aspirin per day for 4 days had been reported. 43 Recently Roncaglioni et al 4 These considerations should be borne in mind when analyzing the results of clinical trials combining aspirin and oral anticoagulants. On the one hand it is not surprising that this drug combination has been reported to be more effective than oral anticoagulants alone in preventing thrombotic complications in patients with aortic ball valves.…”

mentioning

confidence: 99%

Pharmacology of platelet inhibition in humans: implications of the salicylate-aspirin interaction.

Gaetano¹,

Cerletti²,

Dejana³

et al. 1985

Circulation

View full text Add to dashboard Cite

The current dispute over the effects of "low" vs "high"doses of aspirin should take into consideration the pharmacokinetics of this drug. In fact, different pharmaceutical formulations of aspirin may deliver little or no aspirin to the systemic blood. This was the case, for instance, in healthy volunteers taking 320 mg of compressed aspirin or 800 mg of enteric-coated aspirin. In all instances thromboxane B2 generation in serum was fully inhibited. Platelet cyclooxygenase might therefore be effectively acetylated by exposure to aspirin in the portal circulation, whereas vascular cyclooxygenase could be spared. Thus aspirin formulations ensuring complete first-pass deacetylation should be sought rather than "low" or "high" doses of unspecified aspirin formulations. Regardless of the type and dose of aspirin administered, salicylate is formed and accumulates in the circulation. It may antagonize the effects of aspirin on cyclooxygenase, at least in acute conditions. As an example, after administration of 1 g of salicylate to healthy volunteers, when plasma levels of the drug were about 75 ,ug/ml, the effect of 40 mg iv aspirin (given 40 min later) on platelet cyclooxygenase and aggregation was significantly diminished. In contrast, in patients undergoing saphenectomy, the same dose of salicylate (1 g) gave plasma drug levels of about 25 ,ug/ml; salicylate was unable to prevent the inhibitory effect on platelets of 40 mg iv aspirin (given 1 hr later) but did act on vascular prostacyclin. Thus the combination of salicylate with aspirin at an appropriate dose and blood level ratio may result in almost complete dissociation of the drug's effect on platelets and vessels in man. Because the studies outlined in this review address only the short-term outcome of the salicylate-aspirin interaction, the possibility should be tested that inactivation of cyclooxygenase would occur after long-term administration of salicylate-aspirin. A pharmacokinetic approach to the "aspirin dilemma" should also consider the possibility that salicylate and/or its metabolites (e.g., gentisic acid) may interfere with lipoxygenase activity, synthesis of the prothrombin complex coagulation factors, and fibrinolysis. Circulation 72, No. 6, 1185No. 6, -1193No. 6, , 1985 Aspirin, salicylate, and inhibition of platelet aggregation and cyclooxygenase activity. Aspirin inhibits platelet aggregation and the concomitant release reaction.I4 This exciting discovery, made more than 15 years ago, was characterized by three main facts: (1) aspirin was active in man at oral doses as low as 150 mg (about 2 mg/kg), (2) its effects were long lasting (at least 24 to 48 hr), and (3) salicylate, the main metabolite of aspirin, was virtually inactive. The last two observations suggested that the effect of aspirin on platelets was the result of irreversible acetylation. Consequently, the salicylate moiety of aspirin was considered irrelevant for the drug's action on platelets.

show abstract

“…10 ' 13 Aspirin hydrolyzes to acetate and salicylic acid in plasma and tissues so that platelet cyclooxygenase is irreversibly inhibited by ASA-induced acetylation.…”

Section: Discussionmentioning

confidence: 99%

Aspirin treatment reduces platelet resistance to deformation.

Burris¹,

Smith²,

Rao³

et al. 1987

Arteriosclerosis

View full text Add to dashboard Cite

The present investigation has evaluated the influence of aspirin, Its constituents, and other nonsteroldal anti-Inflammatory agents on the resistance of human platelets to aspiration into mlcropipettes. Aspirin Increased the length of platelet extensions Into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestlon of the agent. Other cyclooxygenase inhibitors, Ibuprofen and Indomethacln, did not increase platelet doformablllty. The Influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformablllty. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzole acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiInflammatory agents and cyclooxygenase Inhibitors do not have the same influence on resistance to deformation. (Arteriosclerosis 7:385-388, July/August 1987) R ecent studies in our laboratory have used the technique of micropipette elastimetry to evaluate the resistance of platelets to deformation.12 Investigations into the effects of chilling and of antimitotic agents demonstrated that intact microtubule coils are critical for platelet resistance to aspiration into micropipettes.12 Exposure of platelets to cytochalasin B before aspiration showed that actin microfilament assembly was also important in platelet stability.

show abstract

Inhibition of Adenosine Diphosphate-Induced Secondary Aggregation and Other Platelet Functions by Acetylsalicylic Acid Ingestion

Cited by 311 publications

References 4 publications

Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation

Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation

Pharmacology of platelet inhibition in humans: implications of the salicylate-aspirin interaction.

Aspirin treatment reduces platelet resistance to deformation.

Contact Info

Product

Resources

About