Inhibition of platelet function with clopidogrel, as measured with a novel whole blood impedance aggregometer in horses

Roscher, Katja; Failing, Klaus; Moritz, Andreas

doi:10.1016/j.tvjl.2014.12.028

Cited by 9 publications

(12 citation statements)

References 55 publications

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“…Expectedly, we measured significantly higher AUC levels of the ASPI test and the ADP test in unmedicated animals as compared to medicated pigs. It is known that arachidonic acid (AA) and adenosine diphosphate (ADP), which are used as reagents in the ASPI test and the ADP test of the Multiplate® Analyzer, are able to induce platelet aggregation in other animal species like horses and dogs [40, 41]. Our results indicate that these reagents can also aggregate porcine platelets and thus can be used to examine platelet function and the response to platelet inhibition in pigs.…”

Section: Discussionmentioning

confidence: 78%

Platelet function testing in pigs using the Multiplate® Analyzer

et al. 2019

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For endovascular research pigs are an established animal model. However, experiences regarding analyses of platelet inhibition in pigs using the Multiplate® Analyzer are limited. The aims of the present study were to investigate if (1) the Multiplate® Analyzer is a suitable method for examination of porcine platelet function using manufacturers’ recommendations for human blood, and (2) platelet inhibition can be induced with acetylsalicylic acid (ASA) and clopidogrel in pigs reliably, and if (3) non-responders to one of the drug can be detected. Additionally we examined differences in (4) the effectiveness of ASA between oral administration and intravenous application, and (5) between domestic pigs (German Landrace; GL) and miniature pigs (MP). We investigated platelet function of 36 unmedicated pigs (GL n = 28; MP n = 8). In addition, 32 blood samples taken from medicated pigs (GL n = 15; MP n = 17) were analysed. Platelet inhibition was induced in four different ways: (1) 500 mg ASA intravenously (n = 11), (2) 500 mg ASA intravenously and 450 mg clopidogrel orally (n = 5), (3) 250 mg ASA orally (n = 11), (4) 250 mg ASA orally and 75 mg clopidogrel orally (n = 5). Results of the ASPI and ADP test of the Multiplate® Analyzer subtests in unmedicated and medicated pigs were in a comparable range to results known from humans. Application of ASA decreased the mean values of the ASPI test significantly regardless of the application method. Joined administration of ASA and clopidogrel also decreased the mean values of the ADP test significantly. Both, oral and intravenous administrations of ASA as well as oral administration of clopidogrel effectively inhibited platelet function in pigs. One pig did not respond to clopidogrel. We found no differences between domestic and miniature pigs regarding reference values in unmedicated pigs and the effectiveness of ASA and clopidogrel.

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Section: Discussionmentioning

confidence: 78%

Platelet function testing in pigs using the Multiplate® Analyzer

et al. 2019

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“…The device is established to detect the effects in people to be as good or better as other methods (Siller‐Matula et al., ; Velik‐Salchner et al., ). The principle of whole blood impedance aggregometry has previously been applied in equine studies (Jarvis & Evans, ; Kornreich et al., ), and the Multiplate is suitable detecting the inhibitory effects of clopidogrel on platelet function in horses (Roscher et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…After blood collection, tubes containing hirudin (20 μg/ml, Dynabyte) were stored at rest at room temperature for 30 min. Platelet function was measured by whole blood impedance aggregometry (Multiplate Analyzer, software version V2.03.11) according to the instructions of the manufacturer (Dynabyte GmbH, ) as previously described (Roscher et al., ). Briefly, 300 μl of blood was added to 300 μl saline (0.9%) preheated to 37°C in the test cell.…”

Section: Methodsmentioning

confidence: 99%

“…The use of the whole blood impedance multiple electrode aggregometer (MEA) Multiplate Analyzer (Roche) is well established in human platelet function testing, and the inhibitory effects of aspirin can be reliably and specifically detected via agonists arachidonic acid (AA) and collagen (Chen et al., ; Pedersen et al., ; Penz et al., ; Velik‐Salchner et al., ). The method of whole blood impedance aggregometry has been applied in some equine studies (Jarvis & Evans, ; Kornreich, Enyeart, Jesty, Nydam, & Divers, ), and the Multiplate Analyzer is suitable detecting the inhibitory effects of clopidogrel in horses (Roscher, Failing, & Moritz, ).…”

Section: Introductionmentioning

confidence: 99%

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Suspected aspirin resistance in individual healthy adult warmblood horses

Roscher

Failing

Schenk

et al. 2017

Vet Pharm & Therapeutics

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The reasons for this prospective experimental study were to determine a dosing scheme with loading and maintenance dose of aspirin inducing inhibition of platelet function measured by whole blood impedance aggregometry. Ten horses received aspirin orally in the morning with one loading dose of 4.7-5 mg/kg and maintenance doses of 1-1.3 mg/kg daily the following 4 days. Aggregometries (COLtest, ASPItest, ADPtest) and serum salicylic acid were measured. ASPItest showed significant difference in inhibition at 24 and 48 hr (p < .05) and 96 hr (p < .01). Significant change for ADPtest and COLtest couldn't be detected. Serum salicylic acid concentrations were significantly (p < .01) increased at 6 and 12 hr. Despite this, three horses failed any inhibitory effect of platelet function, suspecting an aspirin resistance. Regarding the other seven horses platelet aggregation induced by ASPItest was reduced between 37% and 100% from baseline at 6 and 12 hr and between 0 and 98% during the next 4 days. Correlations of serum concentration of salicylic acid and aggregometries couldn't be detected. It can be presumed that equine platelets are less susceptible to aspirin what may compromise eventually the anticoagulatory effects and efficacy in preventing and treating diseases with increased platelet activation as endotoxaemia or laminitis.

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“…Hirudin blood samples were analyzed by the use of impedance aggregometry as described previously. 40 Platelet aggregation was measured using 4 different agonists to activate platelets according to the previous manufacturer’s (Dynabyte) information: adenosine diphosphate (6.5 µM final concentration, ADPtest; Roche), ADP + prostaglandin E1 (6.5 µM/9.4 nM final concentration, ADPtestHS; Roche), arachidonic acid (0.75 mM final concentration, ASPItest; Roche), and collagen (1.6 µg/mL final concentration, COLtest; Roche). Spontaneous platelet aggregation (SPA) was also measured by adding isotonic saline instead of a platelet agonist.…”

Section: Methodsmentioning

confidence: 99%

Assessment of platelet biology in equine patients with systemic inflammatory response syndrome

et al. 2020

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In addition to maintaining hemostasis, platelets have an important role in modulating innate and adaptive immune responses. A low platelet count has been found to be a negative prognostic factor for survival in humans and horses with critical illnesses, such as sepsis or systemic inflammatory response syndrome (SIRS). Decreased platelet aggregation, caused by in vivo activation, has been found in human patients with severe sepsis. In our prospective controlled study, we assessed platelet biology in blood samples from 20 equine SIRS cases and 120 healthy control horses. Platelet variables such as platelet count, large platelet count, clumps, plateletcrit, mean platelet volume, and mean platelet component concentration were analyzed by laser flow cytometry (Advia 2120) from K3EDTA blood and from citrate blood. Hirudin blood samples were analyzed by impedance aggregometry (Multiplate analyzer; Roche) for platelet aggregation, including spontaneous aggregation and aggregation by 4 different agonists: adenosine diphosphate (ADPtest), ADP + prostaglandin E1 (ADPtestHS), arachidonic acid (ASPItest), and collagen (COLtest). SIRS cases had significantly lower platelet counts in K3EDTA blood ( p < 0.0001) compared to control horses. There were no significant differences in aggregation values between SIRS cases and controls. Non-surviving SIRS horses did not have statistically significant lower platelet counts or lower aggregation values for COLtest, ADPtest, or ADPtestHS compared to surviving SIRS horses, although 5 non-survivors were thrombocytopenic.

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Inhibition of platelet function with clopidogrel, as measured with a novel whole blood impedance aggregometer in horses

Cited by 9 publications

References 55 publications

Platelet function testing in pigs using the Multiplate® Analyzer

Platelet function testing in pigs using the Multiplate® Analyzer

Suspected aspirin resistance in individual healthy adult warmblood horses

Assessment of platelet biology in equine patients with systemic inflammatory response syndrome

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