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  • Laboratory Assessments of Therapeutic Platelet Inhibition in Endovascular Neurosurgery: Comparing Results of the VerifyNow® P2Y12 Assay to Platelet Mapping Thromboelastography

    Final Number:
    107

    Authors:
    Brian M Corliss MD; Adam J. Polifka MD; Neil S Harris MD, MB, ChB; Brian Lim Hoh MD; W. Christopher Fox MD

    Study Design:
    Clinical trial

    Subject Category:
    Aneurysm/Subarachnoid Hemorrhage

    Meeting: AANS/CNS Cerebrovascular Section 2017 Annual Meeting

    Introduction: Inhibition of platelet aggregation is vital to preventing thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Recent evidence suggests an ideal inhibition range of 70-150 P2Y12 response units (PRU) as measured on the VerifyNow® assay, which relies on photometric measurements of platelet aggregation. Thromboelastography (TEG) with platelet mapping (PMAP) is an alternative assay that directly measures clot formation and mechanical strength. We compare results of PRU to PMAP.

    Methods: Patients with simultaneous or near-simultaneous PRU and PMAP results who underwent cervical carotid artery stenting, intracranial stent-assisted aneurysm coiling, or flow diversion at our institution between August 2015 and October 2016 were identified. PRU results were compared to the TEG maximal amplitude attributable to ADP activity (MA (ADP)) as measured by PMAP. Platelet inhibition was considered therapeutic for MA (ADP) values <50 mm or PRU <194, and ideal for MA (ADP) 30–50 mm or PRU 70–150. The Pearson correlation coefficient was calculated, and sensitivity and specificity of PRU were calculated assuming that the results of PMAP reflected the true degree of platelet inhibition.

    Results: 20 patients were identified with a total of 31 matched sets of PMAP and PRU. The Pearson coefficient for these values was 0.4992 (p=0.004.) The prevalence of clopidogrel non-responders determined by PMAP (10%) matched reported rates (5-12%); PRU demonstrated much higher prevalence (45%.) For detecting a therapeutic level of platelet inhibition, PRU demonstrated sensitivity of 0.57, specificity of 0.67, positive predictive value of 0.94, and negative predictive value of 0.14. Ideal inhibition was concordant in only 27% of observations in which at least one of the results was ideal.

    Conclusions: Agreement between PMAP and PRU regarding degree of platelet inhibition is poor. PRU overestimates clopidogrel resistance, as 86% of patients with PRU >194 actually have a therapeutic level of platelet inhibition.

    Patient Care: VerifyNow is a commonly used test of therapeutic platelet inhibition that guides selection and dose of antiplatelet agents in endovascular neurosurgery. We have demonstrated that this test overestimates the rate of clopidogrel non-responders, and therefore will likely lead to clinicians using excessive doses of clopidogrel in these patients, or switching to medications that potentiate hemorrhagic complications.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) describe the methodological differences between TEG with platelet mapping and the VerifyNow assay, and 2) Describe the limitations of VerifyNow results with respect to endovascular stenting for neurosurgical procedures.

    References: 1. Daou B, Starke RM, Chalouhi N, Barros G, Tjoumakaris S, Rosenwasser RH, Jabbour P. P2Y12 reaction units: Effect on hemorrhagic and thromboembolic complications in patients with cerebral aneurysms treated with the Pipeline embolization device. Neurosurgery 2016 Jan; 78(1): 27-33. 2. Muller I, Besta F, Schultz C, Massberg S, Schonig A, Gawaz M. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thrombosis and Haemostasis 2003 May; 89(5): 783-787. 3. Slavik L, Ulehlova J, Krcova V, Hlusi A, Indrakova J, Hutyra M, Galuszka J, Indrak K. Detection of clopidogrel resistance using ADP induced aggregometry with specific inhibitor PGE1. Clinical laboratory 2014; 60(9): 1475-1480

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