Dataset Information

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein-losing nephropathy.

ABSTRACT:

Background

Dogs with protein-losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs.

Objectives

Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs.

Animals

Six healthy and 14 PLN dogs.

Methods

Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1-week postclopidogrel administration to identify responders or nonresponders. A decrease of ?60% for ADP or ?30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12?weeks after clopidogrel or aspirin administration.

Results

In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs.

Conclusions and clinical importance

Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

SUBMITTER: Shropshire S

PROVIDER: S-EPMC7096639 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein-losing nephropathy.

Shropshire Sarah S Johnson Tyler T Olver Christine C

Journal of veterinary internal medicine 20200125 2

<h4>Background</h4>Dogs with protein-losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs.<h4>Objectives</h4>Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs.<h4>Animals</h4>Six healthy and 14 PLN dogs.<h4>Methods</h4>Platel ...[more]

PMID: 31981378

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Project description:Dual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm.Platelet function testing using whole blood aggregometry (Chronolog 590) was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease) on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP) 5 ?M) and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 ?M) were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP) testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance.Of the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all initial ALRs had an adequate antiplatelet response. The results for clopidogrel revealed that 69% of the CLR were treated effectively by increasing the clopidogrel dose to 150 mg daily. When prasugrel was not available or contraindicated, 12.7% of the remaining low responders showed an adequate result after being switched to ticlopidine. Consequently, by applying the therapy algorithm, we were able to reduce the CLR prevalence by 86.6%. On including prasugrel in the therapy plan, we were finally able to eliminate thienopyridine low response. In addition, no ADP receptor defect was found in this study as a potential reason for CLR. We identified the following factors associated with both CLR and ALR status: acute coronary syndromes, positive troponin values as well as diabetes mellitus and elevated HbA1C values and a higher platelet count. Furthermore, our data revealed for CLR elevated C-reactive protein values and a high PREDICT-score (including an age >65 years, acute coronary syndrome, diabetes mellitus, renal failure, and reduced left ventricular function) as risk factors. The following factors correlated with the risk of ASA low response: patients with elevated hemoglobin, serum creatinine and C-reactive protein values. In addition, medication with nitrates reduced the risk of being CLR. As also holds true for CLR, we found the PREDICT-score to be correlated to the risk of being ALR. However, by far the strongest risk factor for CLR or ALR was the fact of dual resistance.Following a structured therapy plan based on a "test and treat" strategy, the prevalence of clopidogrel or aspirin low response can be significantly reduced and the risk of inadequate dual antiplatelet therapy minimized.

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Dataset Information

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein-losing nephropathy.

Background

Objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein-losing nephropathy.

Similar Datasets

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