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

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.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648925 ◽

1994 ◽

Vol 72 (04) ◽

pp. 622-626 ◽

Cited By ~ 8

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.

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

10.1055/s-0038-1644866 ◽

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.

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

10.1055/s-0038-1644555 ◽

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.

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Platelet Deposition Induced by Severely Damaged Vessel Wall Is Inhibited by a Boroarginine Synthetic Peptide with Antithrombin Activity

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642469 ◽

1994 ◽

Vol 71 (04) ◽

pp. 511-516 ◽

Cited By ~ 14

Author(s):

J J Badimon ◽

D Weng ◽

J H Chesebro ◽

V Fuster ◽

L Badimon

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Synthetic Peptide ◽

Ex Vivo ◽

Thrombus Formation ◽

Blood Platelet ◽

Flow Conditions ◽

Local Flow ◽

Platelet Deposition ◽

Damaged Vessel

SummaryThrombin plays a key role in platelet activation and thrombosis. Specific inhibition of thrombin appears to be one of the best approaches to prevent thrombus formation. We have studied the effects of a synthetic a-aminoboronic acid derivative - [Ac, (D) Phe-Pro-Boro-Arg-Hydrocloric acid] - on platelet deposition on severely damaged arterial wall. Platelet deposition was evaluated under well characterized rheological conditions in an original perfusion chamber and detected by autologous mIn-labeled platelets. The study was performed “in vivo” in a porcine model of arterial thrombosis triggered by severely damaged vessel wall at blood flow conditions mimicking mild stenosis (1690 s−1) and patent (212 s−1) vessels. In addition, ex-vivo platelet aggregation activity was evaluated by whole blood impedance aggregometry using collagen, ADP and thrombin as agonists. The synthetic a-aminoboronic peptide was intravenously administered as a bolus followed by continuous infusion. Ex vivo thrombin-induced whole blood platelet aggregation was totally abolished, while ADP- and Collagen-induced whole blood platelet aggregation was not modified. The effects of the synthetic antithrombin on platelet deposition were evaluated in native blood (non-anticoagulated) conditions and in combination with heparin. Under both experimental conditions, the synthetic peptide significantly inhibited platelet deposition at local flow conditions of both high (1690 s−1) and low (212s−1) shear rates. Our results suggest that specific inhibition of locally generated thrombin might be a good strategy to prevent platelet dependent arterial thrombus formation independently of the local flow shear rate of the area at risk.

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A Prostacyclin-sparing Effect of Indobufen vs. Aspirin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650306 ◽

1996 ◽

Vol 75 (03) ◽

pp. 510-514 ◽

Cited By ~ 5

Author(s):

R De Caterina ◽

D Giannessi ◽

W Bernini ◽

G Lazzerini ◽

M Lavezzari ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Whole Blood ◽

Ex Vivo ◽

Blood Platelet ◽

Tolerability Profile ◽

Double Blind ◽

Baseline Serum ◽

Cyclooxygenase Inhibition ◽

Blood Platelet Aggregation

SummaryIndobufen ((±)-2-[p-(l-oxo-2-insoindolinyl)-phenyI]-butyric acid, indo) is a drug inhibiting platelet function by a reversible block of the arachidonic acid metabolism at the level of cyclooxygenase. Since tolerability profile of such drugs is mostly linked to extra-platelet cyclooxygenase inhibition, we prospectively evaluated the extent of platelet and extra-platelet cyclooxygenase inhibition by in vivo administration of indo in comparison with ASA. We assessed the effects of the two drugs on the ex vivo generation of TXB2 and 6-keto-PGFlΑ in whole blood, as indices of the production of TXA2 and PGI2 (prostacyclin), respectively, either after spontaneous clotting at 37° C for 1 h (Study 1) or after the addition of 2 Μg/ml collagen (Study 2). Generation of 6-keto-PGFlΑ in whole blood is a mixed index of platelet and extra-platelet cyclooxygenase activity, deriving from both platelet and white blood cell arachidonic acid metabolization. Fifteen patients with ischemic heart disease and baseline serum TXB2 levels > 300 ng/ml were allocated to receiving one single administration of either indobufen 200 mg (n = 6) or aspirin 500 mg (n = 9). Whole blood prostanoid generation was assessed at 0,1,2,4,6, 8,12 and 24 h after drug administration (Study 1). Ten healthy male volunteers were allocated to a double-blind, randomized crossover comparison of indo 200 mg b.i.d. vs. ASA 300 mg/d for 7 days (Study 2). Prostanoid generation and whole blood platelet aggregation were performed before and at the end of each study period (Day 0 and Day 7). At each time-point after single dose administration (Study 1), indobufen caused less % inhibition of whole blood 6-keto-PGFlΑ than of TXB2. At 2 h, TXB2 was reduced to a similar extent after ASA (98 ± 4%) and indo (97 ± 6%) (p = N.S.), while inhibition of 6-keto-PGFla was clearly different (> 98% after ASA, 81 ± 2.5% after indo, p < 0.01). After one week of ASA or indo (Study 2) the maximum extent of whole blood platelet aggregation was similarly inhibited (from 17.2 ± 1.4 ohms to 3.6 ± 1.3 ohms with ASA; from 18.3 ± 1.0 ohms to 1.6 ± 0.7 ohms with indo (p ASA vs. indo = N. S.). Despite equal inhibition of whole blood TX production after collagen (from 49.0 ± 4.3 ng/ml to 1.1 ± 0.6 ng/ml with ASA, from 49.8 ± 1.3 ng/ml to 1.4 ± 0.6 ng/ml with indo), again, however, 6-keto-PGFlΑ production was less affected by indo than by ASA (from 409 ± 30 pg/ml to 37 ± 13 pg/ml with ASA, inhibition = 91%; from 396 ± 35 to 318 ± 40 with indo, inhibition = 20%). These differential effects of indo and ASA might lead to a better platelet selectivity, tolerability and benefit/risk profile of indo vs. ASA, which are worthy of further assessment.

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The effect of ex vivo anticoagulants on whole blood platelet aggregation

Platelets ◽

10.1080/09537100802364076 ◽

2009 ◽

Vol 20 (1) ◽

pp. 7-11 ◽

Cited By ~ 63

Author(s):

Madeleine L. Kalb ◽

Lukasz Potura ◽

Gisela Scharbert ◽

Sibylle A. Kozek-Langenecker

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Ex Vivo ◽

Blood Platelet ◽

Blood Platelet Aggregation

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The effect of endothelium-derived nitric oxide on ex vivo whole blood platelet aggregation in man

European Journal of Clinical Pharmacology ◽

10.1007/bf00314917 ◽

1992 ◽

Vol 42 (1) ◽

pp. 37-41 ◽

Cited By ~ 27

Author(s):

P. Vallance ◽

N. Benjamin ◽

J. Collier

Keyword(s):

Nitric Oxide ◽

Platelet Aggregation ◽

Whole Blood ◽

Ex Vivo ◽

Blood Platelet ◽

Blood Platelet Aggregation

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Whole Blood Platelet Aggregation and Release Reaction Testing in Uremic Patients

BioMed Research International ◽

10.1155/2013/486290 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Jay Zeck ◽

Jason Schallheim ◽

Susie Q. Lew ◽

Louis DePalma

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Whole Blood ◽

Low Dose ◽

Reference Range ◽

Atp Release ◽

Blood Platelet ◽

Ckd Stage ◽

Uremic Patients ◽

Blood Platelet Aggregation

Background. Platelet function analysis utilizing platelet-rich plasma and optical density based aggregometry fails to identify patients at risk for uremia associated complications.Methods. We employed whole blood platelet aggregation analysis based on impedance as well as determination of ATP release from platelet granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD) stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims to evaluate this platform in this patient population to determine if abnormalities could be detected.Results. Analysis revealed normal aggregation and ATP release to collagen, ADP, and high-dose ristocetin. ATP release had a low response to arachidonic acid (0.37 ± 0.26 nmoles, reference range: 0.6–1.4 nmoles). Platelet aggregation to low-dose ristocetin revealed an exaggerated response (20.9 ± 18.7 ohms, reference range: 0–5 ohms).Conclusions. Whole blood platelet analysis detected platelet dysfunction which may be associated with bleeding and thrombotic risks in uremia. Diminished ATP release to arachidonic acid (an aspirin-like defect) in uremic patients may result in platelet associated bleeding. An increased aggregation response to low-dose ristocetin (a type IIb von Willebrand disease-like defect) is associated with thrombus formation. This platelet hyperreactivity may be associated with a thrombotic diathesis as seen in some uremic patients.

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