Detection of small inhibitory effects of acetylsalicylic acid (ASA) by platelet impedance aggregometry in whole blood

doi:10.1016/0049-3848(88)90282-4

Thrombosis Research

Volume 51, Issue 1, 1 July 1988, Pages 55-62

https://doi.org/10.1016/0049-3848(88)90282-4 Get rights and content

Abstract

Our investigations have demonstrated on 10 volunteers receiving either 500 mg or 100 mg acetylsalicylic acid (ASA) that a low collagen concentration (1 ug/ml) can best detect the aggregation defect caused by ASA. With the impedance aggregometry the mean inhibition reaches 82% and 52% with 500 mg and 100 mg ASA, respectively.

Collagen at higher concentration (3 μg/ml) as well as ADP 10 and 25 μmol/1 are less sensitive, less than 25% inhibition was recorded. These results suggest that a1 μg/ml concentration of collagen is adequate for the control of the ASA effect up to 6 days after intake of 100 mg. Furthermore, the von Willebrand factor (vWF) dependent platelet aggregation induced by 0.6 and 1.0 mg/ml ristocetin was clearly diminished after ASA. Therefore, a ristocetin screening test in whole blood for vWF disorder is possibly distorted when the test is performed within 6 days from ASA administration.

References (20)

K Koike et al.
Platelet secretion defect in patients with the attention deficit disorder and easy bruising
Blood
(1984)
D.C Cardinal et al.
The electronic aggregometer: a novel device for assessing platelet behavior in blood
J. Pharm. Meth.
(1980)
C.M Ingerman-Wojenski et al.
Difficulty in detecting inhibition of platelet aggregation by the impedance method
Thromb. Res.
(1982)
J.P Dela Cruz et al.
Platelet aggregation in human whole blood after chronic administration of aspirin
Thromb. Res.
(1987)
J.R O'Brien
Effects of salicylates on human platelets
Lancet
(1968)
G.J Roth et al.
Acetylation of prostaglandin synthase by aspirin
E.E Czapek et al.
Intermediate syndrome of platelet dysfunction
Blood
(1978)
J.R O'Brien
What does the optical platelet aggregation test actually measure?
Acta med. Scand. (Suppl)
(1971)
A Gaarder et al.
Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets
Nature
(1961)
G.J Blackwell et al.
Prostacyclin is produced in whole blood
Br. J. Pharmacol.
(1978)

There are more references available in the full text version of this article.

Cited by (25)

Comparison of collagen versus adenosine diphosphate in detecting antiplatelet effect in patients with coronary artery disease
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Citation Excerpt :
One of the receptors is GPVI, which is responsible for platelet signaling and activation leading to thromboxane A2 formation [23]. Indeed, Sathiropas et al. [24] suggested that collagen could be a more specific agonist for detection of the inhibitory effect of ASA as compared with ADP and ristocetin in normal volunteers; That's in accordance with our results to some degree. Kawasaki et al. reported that the difference between ASA responders and ASA non-responders is due to the variations in platelet reactivity to collagen [25].
Widely varying methods of assessing platelet aggregation have resulted in the absence of an established standard approach to assess the effects of antiplatelet drugs. The objective of this study was to compare the roles of collagen and adenosine diphosphate (ADP) in the assessment of effects of aspirin or clopidogrel on platelet aggregation. Sixty patients with documented coronary artery disease were assigned to receive aspirin alone (ASA 100 mg/d) (n = 30) or aspirin-plus-clopidogrel (ASA 100 mg/d + C 75 mg/d) (n = 30). Platelet aggregation assessment by the use of whole blood aggregation tests with collagen or ADP was performed in these patients and 30 age- and gender-matched normal volunteers. When compared with the control group, therapy with ASA or ASA + C resulted in significant inhibition of collagen-induced platelet aggregation (P < 0.001 for each), but there was no statistically significant difference in the results between the ASA and ASA + C groups. When platelet aggregation was induced by ADP, the combined therapy with aspirin and clopidogrel decreased platelet aggregation significantly when compared with aspirin alone (P < 0.001), and no significant difference in the results between the ASA and normal groups was observed. In conclusion, collagen may prove useful to study the effect of aspirin and ADP may be appropriate for assessing the inhibitory effect of clopidogrel.
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The effect of aspirin (ASA) on vWF induced platelet – platelet interaction is unknown. We therefore tested the response of platelets to von Willebrand factor (vWF) coated beads induced platelet aggregation before and after i.v. and oral ASA. 1000 mg ASA was infused to 10 healthy individuals and after a wash-out period 7 volunteers received 100 mg ASA orally over a period of 11 days. Prior to ASA and in regular intervals thereafter we tested the reactivity to vWF-coated beads to assess platelet adhesion/aggregation and the fade-out time of ASA effects on platelets. Considerable interindividual variability in response to vWF-coated beads was observed, both before ASA and after treatment with ASA. The maximal response to vWF-coated beads (Tmax), the time lag, and the slope of the curve were significantly affected by i.v. ASA, whereas 100 mg of ASA had only inconstant effect on Tmax and slope. The absolute reduction of Tmax after ASA depended on the pre-ASA level, while the percentage of the reduction was similar in all individuals. Thus, platelet aggregation induced by vWF-coated beads is impaired by ASA. Furthermore, our data indicate a large interindividual variability of the response to ASA shortly after treatment induction, which becomes more constant after prolonged treatment.
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This paper describes the optimal conditions for simultaneous evaluation of platelet aggregation and secretion capacity in canine whole blood using a Whole Blood Lumi-Aggregometer (Chrono-Log Corporation, Havertown, Pensylvania). For this purpose, the potential influence of several parameters was investigated using collagen, adenosinediphosphate ( $ADP$ ), arachidonic acid ( $AA$ ) and thrombin as platelet agonists.
Results indicate that optimal experimental conditions to obtain reliable results include: allowing blood samples to stand at room temperature 60 minutes after blood collection, analysing samples within 3 hours from time of collection, adjusting platelet numbers to a final concentration of 150 000 μl^–1and mixing the sample with isotonic saline (1:1) before adding the platelet agonist. The use of different platelet agonists offers variable results: collagen (0·5, 1 and 5 μg ml^–1) is suitable for simultaneous platelet aggregation and adenosintriphosphate ( $ATP$ ) secretion measurements; 1 UI ml^–1of thrombin induced maximum $ATP$ secretion; $AA$ (0·5 and 1 mM) and $ADP$ (5, 10 and 25 μM) did not give consistent results.
The method described in this study has important clinical applications since it allows easy and quick platelet function evaluation in pathologic states.
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The effects of two doses of aspirin (75 and 500 mg/day during 1 week) on thrombin generation was investigated in healthy volunteers. Thrombin generation in whole blood was monitored by repeated measurements of prothrombin fragment 1+2 (F1+2) in plasma prepared from untreated whole blood left to clot at 37°C. Experiments with a platelet inhibiting agent (iloprost, a prostacyclinanalogue) and platelet-activating compounds (collagen and a thromboxane analogue), indicated that the formation of thrombin in this system is partly dependent on platelet function. High dose aspirin (500 mg daily) attenuated thrombin generation, whereas low-dose treatment (75 mg daily) failed to attenuate thrombin formation significantly. Collagen-induced platelet aggregation in whole blood, used to monitor antiplatelet effects of aspirin, showed profound inhibition of platelet aggregation already at 75 mg of aspirin; 500 mg did not inhibit platelet aggregation further. Our results show that aspirin suppresses thrombin formation in whole blood in a dose-dependent fashion and that the “antithrombin” effects of aspirin require higher doses than the antiaggregating effects. The mechanism(s) behind the “antithrombin” effects of aspirin is at present unclear but may involve thromboxane-independent mechanisms, such as acetylation of platelet membrane receptors or coagulation factors.

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PaperDetection of small inhibitory effects of acetylsalicylic acid (ASA) by platelet impedance aggregometry in whole blood

Abstract

Blood

J. Pharm. Meth.

Thromb. Res.

Thromb. Res.

Lancet

Acetylation of prostaglandin synthase by aspirin

Intermediate syndrome of platelet dysfunction

Blood

What does the optical platelet aggregation test actually measure?

Acta med. Scand. (Suppl)

Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets

Nature

Prostacyclin is produced in whole blood

Br. J. Pharmacol.

Paper
Detection of small inhibitory effects of acetylsalicylic acid (ASA) by platelet impedance aggregometry in whole blood