Inhibition of Platelet Adherence to Damaged Vessel wall by Drugs

Cazenave, J. P.; Guccione, MA; Packham, Marian A.; Mustard, J. F.

doi:10.1007/978-1-4613-4220-5_47

Cited by 15 publications

(18 citation statements)

References 8 publications

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“…The capacity of platelets to adhere to the subendothelial structures after denudation of the endothelium, has been adequately demonstrated (1)(2)(3)(4)(5)(6) and is generally accepted. Less understood is the ability of platelets to adhere to the intact endothelium either as a consequence of altered flow characteristics, endothelial injury without detachment, or the effect of procoagulants (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Effect of Aspirin on Thrombin-Induced Adherence of Platelets to Cultured Cells from the Blood Vessel Wall

Czervionke¹,

Hoak²,

Fry³

1978

J. Clin. Invest.

191

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A B S T R A C T An in vitro method was used to detect adherence of 51Cr-labeled platelets to monolayers of cultured human endothelial, fibroblast, and smooth muscle cells. Washed platelets did not adhere to untreated or aspirin-treated endothelial monolayers in the absence of thrombin. In contrast, thrombin-induced platelet aggregates adhered to all of the monolayers but adherence to endothelium was significantly less than to the other cells. Additional evidence for adherence of platelets to the endothelium was provided by scanning and transmission electron microscopy. Thrombin-induced platelet adherence to endothelium was inhibited by hirudin. Platelet adherence induced by thrombin was enhanced significantly by treatment of the endothelial monolayer with 1-2 mM aspirin. This increase in adherence was seen even when aspirin-treated platelets were used; adherence values approached those seen with fibroblasts and smooth muscle cells. An aspirin concentration of 0.1 mM was sufficient to block thrombin-induced malonaldehyde production in platelets but it did not interfere with the inhibitory effect of the endothelium against platelet adherence. The effect of aspirin on the endothelium was temporary and inhibitory activity of the endothelium was restored 1 h after aspirin had been removed from the incubation system. The ability of thrombin to cause adherence of platelets to undamaged endothelium, and the potential for aspirin to enhance this adherence have implications for mechanisms which operate in platelet interaction with the blood vessel wall.

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Section: Introductionmentioning

confidence: 99%

Effect of Aspirin on Thrombin-Induced Adherence of Platelets to Cultured Cells from the Blood Vessel Wall

Czervionke¹,

Hoak²,

Fry³

1978

J. Clin. Invest.

191

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“…My ex vivo results are consistent with these. Without exception, and regardless of whether human or rabbit platelets were used, studies of platelet adherence to aortic suben dothelium after incubation of platelets with ASA in vitro have given consistent resultsno effect with erythrocytes present [2,6,7,10,14] but inhibition in their absence [5][6][7], However, findings in studies of adherence to collagen in vitro have been more varied. My results with human platelets adherent to par ticulate collagen are similar to those obtained in studies using washed rabbit platelets ad herent to collagen-coated cylinders [6], With human platelets and methods similar to mine, ASA inhibited platelet-collagen adher ence in two studies [2,3] but not in two oth ers [9,16].…”

Section: Discussionmentioning

confidence: 87%

“…With two exceptions [5,8], inhibition of platelet adherence after the administration of ASA in vivo has not been found; this has applied whether human [9,[11][12][13]15] or rabbit platelets [13,16] were studied and whether adherence to collagen [9,11,16] or to subendothelium [12,13,15] was mea sured. My ex vivo results are consistent with these.…”

Section: Discussionmentioning

confidence: 99%

Platelet Adherence to Collagen

Mant¹

1982

Pathophysiol Haemos Thromb

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Under conditions of low shear and in the absence of laminar flow the addition of acetylsalicylic acid (ASA), but not of sodium salicylate, to human platelet-rich plasma (PRP) in vitro significantly inhibited platelet adherence to collagen (p < 0.001). Inhibition was of similar degree (17%) at ASA concentrations of 10 and 1,000 μM, but was less (10% inhibition) in PRP with erythrocytes added to 40% hematocrit. The ingestion of 600 mg ASA had negligible effect on platelet adherence in whole blood or in PRP. There was no correlation between the effects of ASA on adherence and on platelet aggregation in vitro or ex vivo. It is concluded that the effect of ASA on platelet adherence is unlikely to be important in vivo, except perhaps in vascular sites where flow is non-laminar and where shear rates and/or the physical forces on platelets are low.

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“…Collagen-coated glass segments, or samples of damaged rabbit aorta, were perfused with the platelet suspension in a rotating probe device (Cazenave et al, 1975). This technique allows quantification of platelet monolayer adhesion, while platelet microaggregate formation is suppressed.…”

Section: Methodsmentioning

confidence: 99%

Effect of dazoxiben on platelet‐vessel wall interaction.

Davies¹,

Menys²

1983

Brit J Clinical Pharma

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1 Platelet monolayer adhesion to damaged rabbit aorta and to collagen-coated glass was quantified in a perfusion device. Addition of the thromboxane synthetase inhibitor dazoxiben (UK 37248) 1 and 10 ILM reduced adhesion to damaged blood vessel by about 45% at both concentrations, but did not affect adhesion to collagencoated glass. 2 Measurement by RIA indicated virtual abolition of thromboxane B2 production in the presence of the drug and a slight trend to an increase of 6-oxo-prostaglandin Fla concentration in experiments using aorta. Inhibitory activity of dazoxiben was abolished by previous exposure of the aorta to 15-HPETE(?), an inhibitor of prostacyclin synthetase. 3 The results indicate that dazoxiben inhibits platelet adhesion to vascular subendothelium possibly by promoting synthesis of PGI2 from re-directed platelet endoperoxides.

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Inhibition of Platelet Adherence to Damaged Vessel wall by Drugs

Cited by 15 publications

References 8 publications

Effect of Aspirin on Thrombin-Induced Adherence of Platelets to Cultured Cells from the Blood Vessel Wall

Effect of Aspirin on Thrombin-Induced Adherence of Platelets to Cultured Cells from the Blood Vessel Wall

Platelet Adherence to Collagen

Effect of dazoxiben on platelet‐vessel wall interaction.

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