Monitoring of Antiplatelet Therapy Using Whole Blood Aggregometry: Experiences and Approaches to Dose Adaptation

OBJECTIVEDual antiplatelet therapy is required for the treatment of intracranial aneurysms with the Pipeline embolization device (PED). Platelet function testing (PFT) is often used to assess the efficacy of the antiplatelet regimen prior to PED placement. The optimal impedance values for whole blood aggregometry in this setting have not been defined.METHODSA retrospective review of a prospectively maintained database was performed for the years 2011–2015 to identify patients with intracranial aneurysms treated with the PED who underwent pretreatment PFT using whole blood aggregometry. Antiplatelet therapy was not altered based on PFT results; all patients remained on standard doses of aspirin and clopidogrel. Clinical, radiographic, and laboratory data were analyzed to identify the optimal cutoff impedance value for clopidogrel responsiveness using the receiver operating characteristic curve and Youden’s index.RESULTSForty-nine patients underwent 53 endovascular procedures for the treatment of 76 aneurysms using the PED. The majority of these aneurysms were located in the anterior circulation (90.8%) and affected the internal carotid artery (89.5%). Patients in 30 procedures (56.6%) were identified as clopidogrel responders based on the manufacturer cutoff value (< 6 Ω). Thromboembolic complications occurred in 13 (24.5%) procedures; patients in 6 (11.3%) cases were symptomatic and those in 3 (5.7%) cases had ischemic strokes. Eleven of the 13 (84.6%) thromboembolic complications occurred in clopidogrel nonresponders. An impedance value of ≥ 6 Ω was independently associated with thromboembolic complications. The optimal electrical impedance value was identified as ≥ 6 Ω (sensitivity 84.6%, specificity 70.0%, area under the curve 0.77) for identifying clopidogrel nonresponders.CONCLUSIONSThromboembolic complications are more common following PED placement in patients who do not respond adequately to clopidogrel. Clopidogrel nonresponders can be identified using pretreatment whole blood aggregometry. The optimal cutoff value to categorize a patient as a clopidogrel nonresponder when using whole blood aggregometry is ≥ 6 Ω.

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Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

BMC Research Notes ◽

10.1186/1756-0500-4-106 ◽

2011 ◽

Vol 4 (1) ◽

Cited By ~ 7

Author(s):

Saskia H Meves ◽

Horst Neubauer ◽

Ursula Overbeck ◽

Heinz G Endres

Keyword(s):

Crossover Study ◽

Healthy Volunteers ◽

Antiplatelet Therapy ◽

Whole Blood ◽

Whole Blood Aggregometry

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Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617709086 ◽

2017 ◽

Vol 24 (1) ◽

pp. 151-156 ◽

Cited By ~ 4

Author(s):

Yasushi Nagao ◽

Rikuo Masuda ◽

Akane Ando ◽

Mutsumi Nonaka ◽

Akiko Nishimura ◽

...

Keyword(s):

Platelet Aggregation ◽

Antiplatelet Therapy ◽

Whole Blood ◽

Tooth Extraction ◽

Point Of Care ◽

Adenosine Diphosphate ◽

Blood Platelet ◽

Test Results ◽

Test Sensitivity ◽

Whole Blood Aggregometry

When patients on antiplatelet therapy (APT) require minor invasive surgery, APT is usually continued to limit the risk of thrombosis. However, the possibility of hemostatic difficulties necessitates the monitoring of platelet aggregation to prevent unexpected bleeding. We examined whether whole blood aggregometry as a point-of-care testing (POCT) could be useful as a tool for predicting hemostatic difficulties. Sixty-five patients receiving APT and 15 patients who were not receiving APT were enrolled in the present study; all patients were scheduled to undergo a tooth extraction. Whole blood samples were obtained and were examined using multiple electrode aggregometry. The aggregometry was performed using arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor activating peptide. Hemostatic difficulty was defined as a need for more than 10 minutes of compression to achieve hemostasis. The AA test results were significantly lower in patients treated with aspirin (control: 97.7 [29.0] U, aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly lower in patients treated with a P2Y12 inhibitor (control: 77.7 [21.7] U, P2Y12 inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited hemostatic difficulties. The cutoff values for the prediction of hemostatic difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508) and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study showed that whole blood aggregometry was useful as a POCT for the prediction of hemostatic difficulties after tooth extraction in patients receiving APT.

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Differential antiplatelet effects of angiotensin converting enzyme inhibitors: Ex vivo and in vitro studies using whole blood aggregometry

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(03)82279-9 ◽

2003 ◽

Vol 41 (6) ◽

pp. 272-273

Author(s):

Dirk Skowasch ◽

Melanie Schneider ◽

Stefanie Schrempf ◽

Stefan Krämer ◽

Mario maylahn ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Whole Blood ◽

Enzyme Inhibitors ◽

Ex Vivo ◽

Angiotensin Converting Enzyme Inhibitors ◽

In Vitro Studies ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors ◽

Whole Blood Aggregometry

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Multiple Electrode Whole Blood Aggregometry, PFA-100, and In Vivo Bleeding Time for the Point-of-Care Assessment of Aspirin-Induced Platelet Dysfunction in the Preoperative Setting

Anesthesia & Analgesia ◽

10.1213/ane.0b013e31821acddc ◽

2011 ◽

Vol 113 (1) ◽

pp. 31-39 ◽

Cited By ~ 12

Author(s):

Csilla Jámbor ◽

Klaus-Werner von Pape ◽

Michael Spannagl ◽

Wulf Dietrich ◽

Andreas Giebl ◽

...

Keyword(s):

Whole Blood ◽

Bleeding Time ◽

Point Of Care ◽

Platelet Dysfunction ◽

Care Assessment ◽

Whole Blood Aggregometry ◽

Multiple Electrode

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Whole Blood Aggregometry: A PC-Based System for Clinical Routine Application

Medical Informatics Europe 1991 - Lecture Notes in Medical Informatics ◽

10.1007/978-3-642-93503-9_161 ◽

1991 ◽

pp. 904-907

Author(s):

Wolfgang Schreiner ◽

Michael R. Müller ◽

Wolfgang Premauer ◽

Ernst Wolner

Keyword(s):

Whole Blood ◽

Clinical Routine ◽

Routine Application ◽

Whole Blood Aggregometry

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Balanced hydroxyethylstarch preparations: are they all the same? In-vitro thrombelastometry and whole blood aggregometry

European Journal of Anaesthesiology ◽

10.1097/eja.0b013e32832f5a90 ◽

2009 ◽

Vol 26 (12) ◽

pp. 1020-1025 ◽

Cited By ~ 4

Author(s):

Joachim Boldt ◽

Andinet Mengistu

Keyword(s):

Whole Blood ◽

Whole Blood Aggregometry

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Responsiveness to aspirin in patients with unstable angina pectoris by whole blood aggregometry

International Journal of Clinical Practice ◽

10.1111/j.1742-1241.2008.01976.x ◽

2009 ◽

Vol 63 (3) ◽

pp. 407-416

Author(s):

J. B. Li ◽

H. M. Dong ◽

Z. Jian ◽

X. J. Wu ◽

X. H. Zhao ◽

...

Keyword(s):

Angina Pectoris ◽

Unstable Angina ◽

Whole Blood ◽

Unstable Angina Pectoris ◽

Whole Blood Aggregometry

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Impaired ristocetin–induced Platelet Aggregation in Whole Blood Assessed with a Multiplate© Analyser Suggests a New Mechanism of Antiplatelet Effect of Aspirin and Clopidogrel,

Blood ◽

10.1182/blood.v118.21.3362.3362 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3362-3362 ◽

Cited By ~ 1

Author(s):

Annick Ankri ◽

Anne Baranger ◽

Isabelle Martin-Toutain ◽

Yves Samson ◽

Jean-Philippe Collet ◽

...

Keyword(s):

Platelet Aggregation ◽

Antiplatelet Therapy ◽

Whole Blood ◽

Dual Antiplatelet Therapy ◽

Blood Platelet ◽

Normal Control Group ◽

Control Group ◽

Irreversible Inhibitor ◽

Blood Samples ◽

Before And After

Abstract Abstract 3362 The five channel computerized Whole Blood Aggregation instrument (Multiple Platelet Function Analyzer or Multiplate®), assesses platelet aggregation based on a modified whole blood impedance aggregation method. It permits platelet aggregation to be measured after adding commonly used agonists as arachidonic acid (ASPItest), ADP (ADPtest), collagen (COLtest), ristocetin (RISTOtest) and TRAP (TRAPtest), by detecting changes in electrical resistance in whole blood. Instrument handling is easy. Results are available within 9 minutes. Our objective was to evaluate the effect of aspirin (irreversible inhibitor of COX-1) and/or clopidogrel (irreversible inhibitor of the platelet P2Y12 receptor) on whole blood platelet aggregations induced by the 5 agonists using the Multiplate® in patients treated by aspirin and/or clopidogrel. Patients and controls. Two hundred and twenty two consecutive patients were recruited: 83 treated daily by 75 or 100 mg aspirin (group A); 42 treated daily by 75 mg clopidogrel (group C); 70 treated daily by 75 or 100 mg aspirin plus 75mg clopidogrel (group AC) and 27 who were daily on 100 mg aspirin before coronary intervention were tested 12 h after dual loading dose of aspirin between 75 et 500 mg and 75 to 900 mg clopidogrel according to cardiologists' recommendations: group loading aspirin-clopidogrel (LAC). Among group AC, 23 consecutive patients requiring intracranial stent placement of supra-aortic vessel were tested first at preoperative, without antiplatelet therapy, then 1 month after initiation of daily continuous dual antiplatelet therapy by 100 mg aspirin + 75mg clopidogrel. Ninety six volunteers without pathology or drugs influencing platelet functions constitute the normal control group (N). Blood samples. All patient and controls gave informed consent prior to blood sampling. Blood samples were collected by venipuncture or obtained from the arterial sheath directly into vacutainer Becton Dickinson tube containing 0.129M sodium citrate. Results. Patients under medication showing lower aggregation values than the arbitrary cutoff (fifth percentile of the aggregation in the normal control group was selected for each agonist) were classified as abnormal and having biological sensitivity to the agonist tested. Aggregation values above the cutoff with ASPItest or ADPtest for patients on antiplatelet agents were considered as a persistent platelet aggregation and as a biological resistance. According to the literature, resistance to aspirin was found in 8.6% of patients under aspirin alone or in combination and in 25.1% of patients under clopidogrel alone or in combination. Our main result shows an inhibition in platelet aggregation using ristocetin as agonist for 73.9% of patients taking aspirin alone, for 27.8% on clopidogrel and in 94% of patients receiving combination of the 2 drugs. This inhibition appears after aspirin + clopidogrel intake as we could observe it among patients candidates for intracranial stent placement tested before and after one month of treatment by dual antiplatelet therapy. This effect is not related to von Willebrand Factor (vWF) deficiency since the measurement of ristocetin cofactor activity, and vWF antigen carried out among 14 patients exhibiting an inhibition in whole blood platelet aggregation using RISTOtest were normal and unchanged before and after antiplatelet treatment. VWF is essential platelet-to-platelet interactions which is promoted by the binding of VWF with platelet-receptor glycoprotein IbIX (GPIbIX). Our results suggest: 1) aspirin inhibits the interaction of vWF to GP IbIX. This inhibition appears increased by the association of clopidogrel to aspirin. 2) a new mechanism of inhibition of the platelet function GPIbIX-vWF dependant conjointly to inhibition of cyclooxygenase by aspirin and P2Y12 receptor by clopidogrel.Table I:Biological sensibility according to the five tests (%) in the 4 groups testedGroup (n)ASPItestADPtestCOLtestRISTOtestTRAPtestA (83)84.312.038.373.98.4C (42)38.176.219.227.816.7AC (70)90.074.348.288.222.9LAC (27)100.074.163.0100.029.6 Disclosures: No relevant conflicts of interest to declare.

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