Effects of Acetylsalicylic Acid on Inhibition of Ex Vivo Platelet Aggregation and Secretion by SKF 107260, a Novel GPIIb/IIIa Receptor Antagonist

1994 ◽  
Vol 72 (04) ◽  
pp. 622-626 ◽  
Author(s):  
Martin I Freed ◽  
Steven Boike ◽  
Nevine Zariffa ◽  
Diane K Jorkasky
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Whole Blood ◽  
Ex Vivo ◽  
Atp Release ◽  
Blood Platelet ◽  
Inhibition Of Platelet Aggregation ◽  
Dependent Inhibition ◽  
Platelet Secretion

SummarySKF 107260 is a potent pentapeptide antagonist of the platelet membrane glycoprotein receptor GP IIb/IIIa. The in vitro platelet inhibitory effects of SKF 107260, acetylsalicylic acid (ASA), and their combination, on collagen-induced platelet aggregation and secretion (ATP release) were assessed in human whole blood. Additionally, the con-centration-response relationships for these inhibitors were compared for males and females in order to explore gender differences in platelet responsiveness. SKF 107260 caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations ≥30 nM. ASA also caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations ≥ 1 mg/dl. The addition of ASA 1 mg/dl to increasing concentrations of SKF 107260 resulted in a more pronounced inhibition of platelet aggregation than when either agent was used alone. These data suggest a pharmacologic interaction, especially at SKF 107260 concentrations ≤30 nM. Since ATP release was significantly inhibited at concentrations ≥ 1 nM, platelet secretion appears to be more sensitive than aggregation to inhibition by SKF 107260. These data suggest that platelet secretion in response to collagen is dependent on the aggregation response mediated by GP IIb/IIIa. In conclusion, SKF 107260 is a potent inhibitor of both whole blood platelet aggregation and secretion and these anti-aggregatory effects may be augmented by concomitant ASA administration.

COMPARISON OF THE EFFECT OF ASPIRIN (ASA) AND CHOLINE MAGNESIUM TRISALICYLATE (CMT) ON PLATELET AGGREGATION IN WHOLE BLOOD EX-VIVO

1987 ◽  
Author(s):  
B J Z Danesh ◽  
A R Saniabadi ◽  
R I Russell ◽  
G D O Lowe ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Random Order ◽  
Blood Platelet ◽  
Bleeding Complications ◽  
Double Blind ◽  
Inhibition Of Platelet Aggregation ◽  
Spontaneous Aggregation

Suppression of platelet aggregation by ASA limits the therapeutic use of this drug as an analgesic in patients with bleeding tendencies. CMT is a non-acetylated salicylate derivative with analgesic and anti-inflammatory effect similar to that of ASA. We compared platelet aggregation in human whole blood ex-vivo, three hours after ingestion of ASA and. CMT. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen (lμg/ml) arachidonic acid (AA, 0.5 mM) as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received a single oral dose of ASA and CMT containing 500 mg equivalent salicylate, on two separate occasions, 10 days apart. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen, AA and spontaneous aggregation, whereas such effects were not observed after CMT ingestion.We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

General Medicine: Effects of Aspirin on Platelet Aggregation in Smokers and Nonsmokers

1997 ◽  
Vol 31 (3) ◽  
pp. 290-293 ◽  
Author(s):  
Clarence Chant ◽  
Susan C Fagan ◽  
Sheena K Aurora ◽  
Barry E Gidal ◽  
Rajiv Joseph
Keyword(s):  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Whole Blood ◽  
Ex Vivo ◽  
Smoking Status ◽  
Outcome Measurement ◽  
Tertiary Care ◽  
Atp Release ◽  
General Medicine ◽  
Blood Platelet

Objective To assess the relative antiaggregatory ability of aspirin on platelets of smoking and nonsmoking healthy volunteers. Design Prospective, randomized, crossover study. Setting Tertiary-care teaching institution. Subjects Eighteen healthy smoking and nonsmoking male volunteers. Interventions Each subject received aspirin 325 mg or ticlopidine 250 mg bid as an active control for 7 days in a crossover manner separated by a 1-month washout period. Whole blood platelet aggregation was measured on four occasions, twice at baseline and once after each drug treatment. Outcome Measurement Whole blood ex vivo platelet aggregation in terms of impedance (Ω) and adenosine triphosphate (ATP) release (nmol), as assessed using Lumi-aggregometry. Results Aspirin was associated with significantly less ATP release in both smokers (p = 0.01) and nonsmokers (p = 0.003). No significant differences in platelet aggregation were found between smokers and nonsmokers at baseline or with any treatment phases. Sixty-seven percent and 17% of volunteers receiving ticlopidine and aspirin, respectively, reported adverse effects. Conclusions Twice-daily administration of aspirin for 7 days to healthy volunteers was well tolerated and also reduced platelet aggregation significantly regardless of smoking status.

scholarly journals In vitro effects of dipyridamole and aspirin on whole blood platelet aggregation and ATP release.

Nosotchu ◽  
2000 ◽  
Vol 22 (2) ◽  
pp. 343-347
Author(s):  
Tomomi Nakamura ◽  
Shinichiro Uchiyama ◽  
Masako Yamazaki ◽  
Makoto Iwata
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Atp Release ◽  
Blood Platelet ◽  
In Vitro Effects ◽  
Blood Platelet Aggregation

Effect of Dipyridamole on Spontaneous Platelet Aggregation in Whole Blood Decreases with the Time After Venepuncture: Evidence for the Role of ADP

1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Correlation Coefficient ◽  
Whole Blood ◽  
Blood Platelet ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Adp Receptor ◽  
Spontaneous Platelet Aggregation

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

Dipyridamole Inhibits Platelet Aggregation in Whole Blood

1983 ◽  
Vol 50 (04) ◽  
pp. 852-856 ◽  
Author(s):  
P Gresele ◽  
C Zoja ◽  
H Deckmyn ◽  
J Arnout ◽  
J Vermylen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Significant Negative Correlation ◽  
Significant Inhibition ◽  
Oral Drug ◽  
Human Blood Samples ◽  
Induced Aggregation

SummaryDipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine- 5’-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p <0.001). A statistically significant inhibition of both collagen (p <0.0025) and ADP-induced (p <0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37° C with dipyridamole (3.9 μM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood.Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

Endotoxin-Induced Platelet Activation in Human Whole Blood In Vitro

1988 ◽  
Vol 59 (03) ◽  
pp. 378-382 ◽  
Author(s):  
Gyorgy Csako ◽  
Eva A Suba ◽  
Ronald J Elin
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Atp Release ◽  
Human Platelets ◽  
Lag Phase ◽  
Human Whole Blood ◽  
Dose Dependent

SummaryThe effect of purified bacterial endotoxin was studied on human platelets in vitro. In adding up to 1 μg/mL of a highly purified endotoxin, we found neither aggregation nor ATP release in heparinized or citrated human platelet-rich plasma. On the other hand, endotoxin at concentrations as low as a few ng/mL (as may be found in septic patients) caused platelet aggregation in both heparinized and citrated human whole blood, as monitored by change in impedance, free platelet count, and size. Unlike collagen, the platelet aggregation with endotoxin occurred after a long lag phase, developed slowly, and was rarely coupled with measurable release of ATP. The platelet aggregating effect of endotoxin was dose-dependent and modified by exposure of the endotoxin to ionizing radiation. Thus, the activation of human platelets by “solubilized” endotoxin in plasma requires the presence of other blood cells. We propose that the platelet effect is mediated by monocytes and/or neutrophils stimulated by endotoxin.

scholarly journals Erythropoietin does not increase whole-blood platelet aggregation in vitro

1994 ◽  
Vol 9 (5) ◽  
pp. 556-558
Author(s):  
J. E. Taylor ◽  
J. J. F. Belch ◽  
I. S. Henderson ◽  
W. K. Stewart
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Blood Platelet ◽  
Blood Platelet Aggregation

Therapeutic Potential of Choline Magnesium Trisalicylate as an Alternative to Aspirin for Patients with Bleeding Tendencies

1987 ◽  
Vol 32 (6) ◽  
pp. 167-168 ◽  
Author(s):  
B.J.Z. Danesh ◽  
A.R. Saniabadi ◽  
R.I. Russell ◽  
G.D.O. Lowe
Keyword(s):  
Salicylic Acid ◽  
Platelet Aggregation ◽  
Whole Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Random Order ◽  
Bleeding Complications ◽  
Double Blind ◽  
Inhibition Of Platelet Aggregation ◽  
Spontaneous Aggregation

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p<0.005), AA (p<0.01) and spontaneous aggregation (p<0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

MEASURING WHOLE BLOOD PLATELET AGGREGATION AND ATP-RELEASE WITH A CHRONO-LOG WHOLE BLOOD LUMI-AGGREGOMETER: EFFECT OF STORAGE TIME OF BLOOD SAMPLES

1987 ◽  
Author(s):  
F C Sieders ◽  
A C v Houwelingen ◽  
G Hornstra
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Storage Time ◽  
Bleeding Time ◽  
Atp Release ◽  
Blood Platelet ◽  
Blood Samples ◽  
Before And After ◽  
Positive Correlations ◽  
Blood Platelet Aggregation

The influence of storing blood for either one or two hours after blood sampling, on whole blood platelet aggregation and ATP-release was measured with a Chrono-log whole blood lumi-aggregometer, in 21 healthy male volunteers. Storage of blood samples, gently revolving at 37 °C in an incubator for one hour, caused a significant increase in aggregation and release as compared with results obtained immediately after sampling. After two hours' storage, the values had returned to their initial levels.Significant positive correlations were seen between values obtained before and after storage of blood, and between various aggregation and release parameters. In this study, bleeding time nor hematocrit values were significantly correlated with the aggregation and release parameters. The considerable influence of storage time on whole blood platelet aggregation and ATP-release underlines the importance of performing these determinations immediately after sampling, or possibly after a standardized storage time. Otherwise, comparison of results -obtained either in clinical situations or in trials - will increase variability as a result of which false conclusions may be obtained. This will be illustrated in a small trial using paracetamol.

Comparison Of The Effects Of Aspirin In Humans Ex Vivo In Platelet-Rich Plasma And Whole Blood

1981 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Trisodium Citrate ◽  
Blood Platelet ◽  
Maximal Response ◽  
Blood Samples ◽  
Platelet Concentration

The effect of aspirin on human platelet function is usually assessed using platelet-rich plasma (PRP). Some preliminary results in vitro suggested that the effect of aspirin appears to be greater in PRP than whole blood. To explore this possibility further, a comparison of the effect of aspirin in humans ex vivo has been made taking measurements simultaneously in whole blood and PRP at 2 platelet concentrations. Blood samples (36ml) were drawn from 7 male volunteers after a light breakfast. Each took 300mg soluble aspirin and blood samples were drawn again 2 hours later. Blood was mixed with 0.1 volumes 129nM trisodium citrate. Some (30ml) was then centrifuged to prepare PRP and platelet -poor plasma (PPP) by standard techniques. Platelet concentration of some PRP was adjusted with PPP to equal that of the corresponding blood sample; the rest was adjusted to 350,000 per μl. Aggregation in response to collagen (Horm, Munich) was measured photometrically at 37°. Aggregation in 0.5ml aliquots of whole blood was measured after 4 min stirring with 154mM NaCl (control) or collagen at 37° as the fall in single platelet count determined using an Ultraflo- 100 whole blood platelet counter (Clay Adams). The concentrations of collagen producing a 50% maximal response (EC50) in PRP and blood were determined. Dose-ratios for each volunteer were calculated by dividing the EC50 obtained after aspirin by the corresponding value obtained before aspirin.The effect of aspirin was significantly (p<0.001) less in blood than PRP. Whether or not the results in whole blood more closely reflect the effect of aspirin in vivo remains to be determined.

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