scholarly journals Determination of Aspirin Responsiveness by Use of Whole Blood Platelet Aggregometry

2007 ◽  
Vol 53 (4) ◽  
pp. 614-619 ◽  
Author(s):  
Boris T Ivandic ◽  
Evangelos Giannitsis ◽  
Philipp Schlick ◽  
Peter Staritz ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Whole Blood ◽  
Stable Coronary Artery Disease ◽  
Blood Platelet ◽  
Platelet Inhibition ◽  
Impedance Aggregometry ◽  
Platelet Aggregometry ◽  
Healthy Control ◽  
Artery Disease

Abstract Background: Insufficient platelet inhibition is associated with an increased cardiovascular risk in up to 30% of patients taking regular doses of aspirin. We describe an assay to study aspirin responsiveness. Methods: We performed impedance aggregometry on diluted whole blood with 1 mg/L collagen and 0.5 mmol/L arachidonic acid (AA). We measured thromboxane B2 (TXB2) by RIA. We examined 66 healthy control individuals, 144 aspirin users with stable coronary artery disease (CAD), and 245 CAD patients treated with aspirin and clopidogrel. Nonresponsive samples were incubated with excess dl-lysinmonoacetylsalicylic acid. Results: Assay imprecision (CV) was 9.8% and 8.2% at mean (SD) 6-min impedance of 13.7 (2.8) Ω and 13.6 (2.3) Ω for collagen and AA, respectively. Collagen induced stronger aggregation (P = 0.0199) in women [n = 28, 14.6 (2.4) Ω] than in men [n = 38, 13.1 (2.9) Ω], even after sample incubation with 0.1 mmol/L acetylsalicylic acid (ASA) or 1 μmol/L terbogrel, a combined inhibitor of thromboxane synthase and receptors. The sex association persisted in aspirin users, but not if clopidogrel was also taken. A 6-min impedance >8 Ω with collagen (mean − 2 SD of the controls) was taken as evidence of nonresponsiveness, particularly if incubation with ASA did not inhibit aggregation further (>2 Ω). Compared with AA, collagen identified more nonresponsive samples among aspirin users (15%) and CAD patients who also received clopidogrel (10%). Incubation with ASA improved inhibition of aggregation in 70% of samples and consistently reduced TXB2 formation during aggregation. Conclusions: Impedance aggregometry may prove useful to study aspirin responsiveness, and incubation with ASA may help to identify nonresponders and classify resistance.

Multiple electrode aggregometry: A new device to measure platelet aggregation in whole blood

2006 ◽  
Vol 96 (12) ◽  
pp. 781-788 ◽  
Author(s):  
Andreas Calatzis ◽  
Sandra Penz ◽  
Hajna Losonczy ◽  
Wolfgang Siess ◽  
Orsolya Tóth
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Blood Platelet ◽  
Platelet Inhibition ◽  
New Device ◽  
Platelet Aggregometry ◽  
Spontaneous Platelet Aggregation ◽  
Induced Aggregation ◽  
Blood Platelet Aggregation ◽  
Multiple Electrode

SummarySeveral methods are used to analyse platelet function in whole blood. A new device to measure whole blood platelet aggregation has been developed, called multiple electrode platelet aggregometry (MEA). Our aim was to evaluate MEA in comparison with the single platelet counting (SPC) method for the measurement of platelet aggregation and platelet inhibition by aspirin or apyrase in diluted whole blood. Platelet aggregation induced by different concentrations of ADP, collagen and TRAP-6 and platelet inhibition by apyrase or aspirin were determined in citrateor hirudin-anticoagulated blood by MEA and SPC. MEA indicated that spontaneous platelet aggregation was lower, and stimulated platelet aggregation was higher in hirudin- than citrate-anticoagulated blood. In hirudin-anticoagulated, but not citrate-anticoagulated blood, spontaneous platelet aggregation measured by MEA was inhibited by apyrase. For MEA compared with SPC the dose response-curves of agonist-induced platelet aggregation in citrate- and hirudin-blood showed similar EC50 values for TRAP, and higher EC50 values for ADP (non-significant) and collagen (p<0.05). MEA and the SPC method gave similar results concerning platelet-inhibition by apyrase and aspirin. MEA was more sensitive than SPC to the inhibitory effect of aspirin in collagen-induced aggregation. In conclusion, MEA is an easy, reproducible and sensitive method for measuring spontaneous and stimulated platelet aggregation, and evaluating antiplatelet drugs in diluted whole blood. The use of hirudin as an anticoagulant is preferable to the use of citrate. MEA is a promising technique for experimental and clinical applications.

scholarly journals Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor

2006 ◽  
Vol 52 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Boris T Ivandic ◽  
Philipp Schlick ◽  
Peter Staritz ◽  
Kerstin Kurz ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Whole Blood ◽  
Adenosine Monophosphate ◽  
Blood Platelet ◽  
P2y12 Receptor ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Impedance Aggregometry ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 μmol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 μmol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) Ω. The mean − 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance ≤5 Ω and &gt;5 Ω, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann–Whitney U-test) was given to responders (median, 450 mg) than nonresponders (median, 300 mg). Age and cardiovascular diagnosis showed no significant associations. Conclusions: Impedance aggregometry using 5 μmol/L ADP is a useful tool for studying clopidogrel responsiveness. MeSAMP allows characterization of responsiveness “on treatment” and may be useful for optimizing clopidogrel dosing.

Serial Determinations of PF4 and βTG: Comparisons Between Multiple Venipunctures vs a Catheter Infusion System

1988 ◽  
Vol 59 (03) ◽  
pp. 491-494 ◽  
Author(s):  
William Strauss ◽  
Guiseppe Cella ◽  
Charles Myers ◽  
Arthur A Sasahara
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Sampling Technique ◽  
Platelet Factor ◽  
Specific Proteins ◽  
Artery Disease ◽  
The Impact ◽  
Infusion System

SummaryPlatelet factor 4 (PF4) and beta thromboglobulin (βTG) are platelet-specific proteins which are released upon platelet aggregation and which can be accurately measured by radioimmunoassay. We devised a catheter-infusion system that enables serial determinations of these proteins.In 20 subjects (10 healthy volunteers and 10 patients with stable coronary artery disease), we compared samples collected by individual venipunctures with those simultaneously obtained by means of a simple catheter-infusion system. At least 5 samples were obtained over a period of time which was as long as 60 min, and at least 30 min. Subjects with stable coronary artery disease were selected so that they would be expected to have stable and normal PF4 and βTG levels. Thus, elevations of either PF4 or βTG would represent artifacts secondary to sampling technique.Analysis of the results demonstrated that the catheter-infusion system was equivalent to individual venipunctures for determination of PF4 and βTG . 16.8% of samples obtained via the catheter and 17.2% of those obtained by individual venipunctures were spuriously elevated.A second series of studies were performed to refine the technique further by examining the impact of infusion rate and the addition of citrate phosphate dextrose (CPD) to the infusate. Ten additional subjects had catheter systems utilized in both arms simultaneously. The addition of CPD resulted in significantly less abnormal values at slower infusion rates (1 and 2.5 cc/min). At 5 cc/min D5/w or saline alone are suitable.These investigations confirm that this simple catheter system is equivalent to individual venipunctures for determination of PF4 and βTG while avoiding patient discomfort. Also noted was the fact that a high percentage of determinations could be spuriously elevated by either technique under clinical demands. Thus, multiple determinations from the same subject are necessary to assure reproducibility.

scholarly journals OUR EXPERIENCE OF OPTIMIZATION AND LEGITIMIZATION OF HEART TEAM WORK (MEDICAL CONSULTATION FOR DETERMINATION OF TREATMENT MANAGEMENT IN PATIENTS WITH ISCHEMIC HEART DISEASE)

2016 ◽  
Vol 175 (2) ◽  
pp. 94-97
Author(s):  
M. Yu. Kaputin ◽  
A. V. Biryukov ◽  
V. Yu. Ul’Chenko
Keyword(s):  
Coronary Artery Disease ◽  
Heart Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Team Work ◽  
Heart Team ◽  
Saint Petersburg ◽  
Artery Disease ◽  
Medical University

The article raises the problem of optimization and legitimization of work of the Heart Team. It also described the background and international experience, provided an overview of the recent international guidelines in relation to management of revasculization in patients with stable coronary artery disease. The article presents an experience of the I. P.Pavlov First Saint-Petersburg State Medical University.

Abstract 4448: Clopidogrel Effect Depends on Body Weight and Abolishes Platelet Leukocyte Interaction in Patients with Coronary Artery Disease Treated by Stenting

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Philipp Diehl ◽  
Christoph Olivier ◽  
Christoph Halscheid ◽  
Thomas Helbing ◽  
Christoph Bode ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Body Weight ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
Obese Patients ◽  
Platelet Activity ◽  
Impedance Aggregometry ◽  
Increased Risk ◽  
Leukocyte Counts ◽  
Artery Disease

Background: Poor response to aspirin and clopidogrel has been associated with an increased risk for thrombotic events after PCI. The optimal dose of clopidogrel is unknown as platelet aggregability (PA) is not routinely measured in clopidogrel treated patients. Methods and Results : In order to assess potential mechanisms of clopidogrel responsiveness we have performed bedside platelet impedance aggregometry in patients with stable coronary artery disease (group CAD; n=62) and patients who underwent elective PCI (group PCI; n=90) compared to control individuals in whom coronary artery disease was excluded by coronary angiography (group control; n=28). Control patients did not receive antiplatelet therapy, CAD patients were treated with aspirin 100mg/d, and PCI patients with aspirin 100mg/d and clopidogrel 75mg/d. Impedance aggregometry was performed using arachidonic acid [AA] (final conc [fc]: 0.5mM) or ADP (fc: 6.5μM) and the area under the curve (AUC) was quantified to detect the effect of aspirin or clopidogrel, respectively. Indeed, PA was specifically reduced by either drug (AA: [control vs. CAD vs. PCI] 877±300 vs. 183±134 vs. 111±90; ADP: [control vs. PCI] 725±275 vs. 288±174 AUC). We detected a negative correlation between body weight and clopidogrel response (r=0.28; p=0.008), suggesting that clopidogrel may have been underdosed in obese patients. Furthermore, we found a positive correlation between leukocyte counts and PA (r=0.4, p=0.028) confirming that platelets and leucocytes interact functionally. Administration of clopidogrel abolished this interaction as detected by comparison of control individuals with PCI patients but also in intra-individual follow-up tests before and after introduction of clopidogrel. Conclusion: Impedance aggregometry is useful to assess PA routinely. Dosage of clopidogrel may need to be adjusted in obese patients. PA depends on leukocyte counts confirming that platelet activity is modulated by leukocytes; this interaction is effectively inhibited by clopidogrel.

scholarly journals Genetic Polymorphisms Impact Response to Clopidogrel in Feline Hypertrophic Cardiomyopathy

2021 ◽  
Author(s):  
Yu Ueda ◽  
Ronald Li ◽  
Nghi Nguyen ◽  
Eric Ontiveros ◽  
Samantha Fousse ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Hypertrophic Cardiomyopathy ◽  
Whole Blood ◽  
Plasma Concentrations ◽  
Blood Platelet ◽  
Platelet Inhibition ◽  
Platelet Aggregometry ◽  
Clopidogrel Therapy ◽  
Adp Receptor ◽  
The Impact

Abstract Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY:A236G variant.

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