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Published in: Clinical Neuroradiology 4/2021

01-12-2021 | Intracranial Aneurysm | Original Article

Dual Testing to Achieve Low On-treatment Platelet Reactivity for Aneurysm Embolization

Authors: Halitcan Batur, Mehmet A. Topcuoglu, Sinan Balci, Ethem M. Arsava, Anil Arat

Published in: Clinical Neuroradiology | Issue 4/2021

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Abstract

Background and Purpose

Although point-of-care tests are used extensively to test platelet function before endovascular aneurysm treatment, their use and validity are still debated. We compared the results of two point-of-care tests (VerifyNow® and Multiplate®) for assessing patients treated with stents and flow diverters and determined their relation to periprocedural complications.

Methods

All patients undergoing treatment of intracranial aneurysms were tested using both methods and were retrospectively evaluated. Patients with acute subarachnoid hemorrhage and those who had to be maintained on anticoagulants for unrelated diseases were excluded. An acceptable level of platelet inhibition was required on both tests to commence with treatment, otherwise antiplatelet medication was adjusted to reach this level.

Results

Mean PRU (platelet reactivity units) and ADP AUC (adenosine diphosphate area under the aggregation curve) were 68 ± 66 and 23 ± 15, respectively, in 295 patients. Both tests showed a good correlation (r = 0.45). Both tests were able to predict hemorrhagic events but not ischemic events. When patients with very low reactivity (PRU < 60) were compared to the rest of the group, there were more hemorrhagic events in the first group but the overall rate of complications were similar (p = 0.27).

Conclusion

In this largest study comparing two widely used commercial platelet function tests, the correlation between the tests were less than ideal; however, the very low platelet reactivity attained by the help of dual platelet testing did not result in an increased overall complication rate.
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Literature
1.
go back to reference Galal A, Bahrassa F, Dalfino JC, Boulos AS. Stent-assisted treatment of unruptured and ruptured intracranial aneurysms: clinical and angiographic outcome. Br J Neurosurg. 2013;27:607–16.CrossRefPubMed Galal A, Bahrassa F, Dalfino JC, Boulos AS. Stent-assisted treatment of unruptured and ruptured intracranial aneurysms: clinical and angiographic outcome. Br J Neurosurg. 2013;27:607–16.CrossRefPubMed
2.
go back to reference Lee DH, Arat A, Morsi H, Shaltoni H, Harris JR, Mawad ME. Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol. 2008;29:1389–94.CrossRefPubMedPubMedCentral Lee DH, Arat A, Morsi H, Shaltoni H, Harris JR, Mawad ME. Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol. 2008;29:1389–94.CrossRefPubMedPubMedCentral
4.
go back to reference Goh C, Churilov L, Mitchell P, Dowling R, Yan B. Clopidogrel hyper-response and bleeding risk in neurointerventional procedures. AJNR Am J Neuroradiol. 2013;34:721–6.CrossRefPubMedPubMedCentral Goh C, Churilov L, Mitchell P, Dowling R, Yan B. Clopidogrel hyper-response and bleeding risk in neurointerventional procedures. AJNR Am J Neuroradiol. 2013;34:721–6.CrossRefPubMedPubMedCentral
5.
go back to reference Karaźniewicz-Łada M, Danielak D, Burchardt P, Kruszyna L, Komosa A, Lesiak M, Główka F. Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases. Clin Pharmacokinet. 2014;53:155–64.CrossRefPubMed Karaźniewicz-Łada M, Danielak D, Burchardt P, Kruszyna L, Komosa A, Lesiak M, Główka F. Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases. Clin Pharmacokinet. 2014;53:155–64.CrossRefPubMed
6.
go back to reference Delgado Almandoz JE, Crandall BM, Scholz JM, Fease JL, Anderson RE, Kadkhodayan Y, Tubman DE. Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline Embolization Device. J Neurointerv Surg. 2013;5 Suppl 3:iii3–10.CrossRefPubMed Delgado Almandoz JE, Crandall BM, Scholz JM, Fease JL, Anderson RE, Kadkhodayan Y, Tubman DE. Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline Embolization Device. J Neurointerv Surg. 2013;5 Suppl 3:iii3–10.CrossRefPubMed
7.
go back to reference Comin J, Kallmes DF. Platelet-function testing in patients undergoing neurovascular procedures: caught between a rock and a hard place. AJNR Am J Neuroradiol. 2013;34:730–4.CrossRefPubMedPubMedCentral Comin J, Kallmes DF. Platelet-function testing in patients undergoing neurovascular procedures: caught between a rock and a hard place. AJNR Am J Neuroradiol. 2013;34:730–4.CrossRefPubMedPubMedCentral
8.
go back to reference Skukalek SL, Winkler AM, Kang J, Dion JE, Cawley CM, Webb A, Dannenbaum MJ, Schuette AJ, Asbury B, Tong FC. Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis. J Neurointerv Surg. 2016;8:58–65.CrossRefPubMed Skukalek SL, Winkler AM, Kang J, Dion JE, Cawley CM, Webb A, Dannenbaum MJ, Schuette AJ, Asbury B, Tong FC. Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis. J Neurointerv Surg. 2016;8:58–65.CrossRefPubMed
9.
go back to reference Müller-Schunk S, Linn J, Peters N, Spannagl M, Deisenberg M, Brückmann H, Mayer TE. Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting. AJNR Am J Neuroradiol. 2008;29:786–91.CrossRefPubMedPubMedCentral Müller-Schunk S, Linn J, Peters N, Spannagl M, Deisenberg M, Brückmann H, Mayer TE. Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting. AJNR Am J Neuroradiol. 2008;29:786–91.CrossRefPubMedPubMedCentral
10.
go back to reference Flechtenmacher N, Kämmerer F, Dittmer R, Budde U, Michels P, Röther J, Eckert B. Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate. AJNR Am J Neuroradiol. 2015;36:1953–8.CrossRefPubMedPubMedCentral Flechtenmacher N, Kämmerer F, Dittmer R, Budde U, Michels P, Röther J, Eckert B. Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate. AJNR Am J Neuroradiol. 2015;36:1953–8.CrossRefPubMedPubMedCentral
11.
go back to reference Bender MT, Zarrin DA, Campos JK, Jiang B, Chandra A, Vo CD, Caplan JM, Huang J, Tamargo RJ, Lin LM, Colby GP, Coon AL. Precision of VerifyNow P2Y12 Assessment of Clopidogrel Response in Patients Undergoing Cerebral Aneurysm Flow Diversion. Neurosurgery. 2019;85:543–9.CrossRefPubMed Bender MT, Zarrin DA, Campos JK, Jiang B, Chandra A, Vo CD, Caplan JM, Huang J, Tamargo RJ, Lin LM, Colby GP, Coon AL. Precision of VerifyNow P2Y12 Assessment of Clopidogrel Response in Patients Undergoing Cerebral Aneurysm Flow Diversion. Neurosurgery. 2019;85:543–9.CrossRefPubMed
12.
go back to reference Jiang B, Bender MT, Westbroek EM, Campos JK, Lin LM, Xu R, Tamargo RJ, Huang J, Colby GP, Coon AL. Procedural complexity independent of P2Y12 reaction unit (PRU) values is associated with acute in situ thrombosis in Pipeline flow diversion of cerebral aneurysms. Stroke Vasc Neurol. 2018;3:169–75.CrossRefPubMedPubMedCentral Jiang B, Bender MT, Westbroek EM, Campos JK, Lin LM, Xu R, Tamargo RJ, Huang J, Colby GP, Coon AL. Procedural complexity independent of P2Y12 reaction unit (PRU) values is associated with acute in situ thrombosis in Pipeline flow diversion of cerebral aneurysms. Stroke Vasc Neurol. 2018;3:169–75.CrossRefPubMedPubMedCentral
13.
go back to reference Kashiwazaki D, Kuwayama N, Akioka N, Hayakawa Y, Kuroda S. The roles and issues of P2Y12 percent inhibition assessed by VerifyNow assay for patients undergoing Neurointervention: a prospective study. J Stroke Cerebrovasc Dis. 2014;23:1830–6.CrossRefPubMed Kashiwazaki D, Kuwayama N, Akioka N, Hayakawa Y, Kuroda S. The roles and issues of P2Y12 percent inhibition assessed by VerifyNow assay for patients undergoing Neurointervention: a prospective study. J Stroke Cerebrovasc Dis. 2014;23:1830–6.CrossRefPubMed
14.
go back to reference Nishi H, Nakahara I, Matsumoto S, Hashimoto T, Ohta T, Sadamasa N, Ishibashi R, Gomi M, Saka M, Miyata H, Watanabe S, Okata T, Sonoda K, Kouge J, Ishii A, Nagata I, Kira J. Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy. J Neurointerv Surg. 2016;8:949–53.CrossRefPubMed Nishi H, Nakahara I, Matsumoto S, Hashimoto T, Ohta T, Sadamasa N, Ishibashi R, Gomi M, Saka M, Miyata H, Watanabe S, Okata T, Sonoda K, Kouge J, Ishii A, Nagata I, Kira J. Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy. J Neurointerv Surg. 2016;8:949–53.CrossRefPubMed
15.
go back to reference Nakagawa I, Park HS, Yokoyama S, Wada T, Hironaka Y, Motoyama Y, Takayama K, Kichikawa K, Nakase H. Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures. J Stroke Cerebrovasc Dis. 2016;25:163–71.CrossRefPubMed Nakagawa I, Park HS, Yokoyama S, Wada T, Hironaka Y, Motoyama Y, Takayama K, Kichikawa K, Nakase H. Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures. J Stroke Cerebrovasc Dis. 2016;25:163–71.CrossRefPubMed
16.
go back to reference Becske T, Brinjikji W, Potts MB, Kallmes DF, Shapiro M, Moran CJ, Levy EI, McDougall CG, Szikora I, Lanzino G, Woo HH, Lopes DK, Siddiqui AH, Albuquerque FC, Fiorella DJ, Saatci I, Cekirge SH, Berez AL, Cher DJ, Berentei Z, Marosfoi M, Nelson PK. Long-Term Clinical and Angiographic Outcomes Following Pipeline Embolization Device Treatment of Complex Internal Carotid Artery Aneurysms: Five-Year Results of the Pipeline for Uncoilable or Failed Aneurysms Trial. Neurosurgery. 2017;80:40–8.CrossRefPubMed Becske T, Brinjikji W, Potts MB, Kallmes DF, Shapiro M, Moran CJ, Levy EI, McDougall CG, Szikora I, Lanzino G, Woo HH, Lopes DK, Siddiqui AH, Albuquerque FC, Fiorella DJ, Saatci I, Cekirge SH, Berez AL, Cher DJ, Berentei Z, Marosfoi M, Nelson PK. Long-Term Clinical and Angiographic Outcomes Following Pipeline Embolization Device Treatment of Complex Internal Carotid Artery Aneurysms: Five-Year Results of the Pipeline for Uncoilable or Failed Aneurysms Trial. Neurosurgery. 2017;80:40–8.CrossRefPubMed
17.
go back to reference Raymond J, Gentric JC, Darsaut TE, Iancu D, Chagnon M, Weill A, Roy D. Flow diversion in the treatment of aneurysms: a randomized care trial and registry. J Neurosurg. 2017;127:454–62.CrossRefPubMed Raymond J, Gentric JC, Darsaut TE, Iancu D, Chagnon M, Weill A, Roy D. Flow diversion in the treatment of aneurysms: a randomized care trial and registry. J Neurosurg. 2017;127:454–62.CrossRefPubMed
18.
go back to reference Liu JM, Zhou Y, Li Y, Li T, Leng B, Zhang P, Liang G, Huang Q, Yang PF, Shi H, Zhang J, Wan J, He W, Liang C, Zhu G, Xu Y, Hong B, Yang X, Bai W, Tian Y, Zhang H, Li Z, Li Q, Zhao R, Fang Y, Zhao K; PARAT investigators. Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter: A Multicenter, Randomized, Controlled Clinical Trial (PARAT). AJNR Am J Neuroradiol. 2018;39:807–16.CrossRefPubMedPubMedCentral Liu JM, Zhou Y, Li Y, Li T, Leng B, Zhang P, Liang G, Huang Q, Yang PF, Shi H, Zhang J, Wan J, He W, Liang C, Zhu G, Xu Y, Hong B, Yang X, Bai W, Tian Y, Zhang H, Li Z, Li Q, Zhao R, Fang Y, Zhao K; PARAT investigators. Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter: A Multicenter, Randomized, Controlled Clinical Trial (PARAT). AJNR Am J Neuroradiol. 2018;39:807–16.CrossRefPubMedPubMedCentral
19.
20.
go back to reference DeGrote JR, Olafson EM, Drofa A, Kouznetzov E, Manchak M, Leedahl ND, Leedahl DD. Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series. Can J Hosp Pharm. 2018;71:349–55.PubMedPubMedCentral DeGrote JR, Olafson EM, Drofa A, Kouznetzov E, Manchak M, Leedahl ND, Leedahl DD. Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series. Can J Hosp Pharm. 2018;71:349–55.PubMedPubMedCentral
21.
go back to reference Choi HH, Lee JJ, Cho YD, Han MH, Cho WS, Kim JE, An SJ, Mun JH, Yoo DH, Kang HS. Antiplatelet Premedication for Stent-Assisted Coil Embolization of Intracranial Aneurysms: Low-Dose Prasugrel vs Clopidogrel. Neurosurgery. 2018;83:981–8.CrossRefPubMed Choi HH, Lee JJ, Cho YD, Han MH, Cho WS, Kim JE, An SJ, Mun JH, Yoo DH, Kang HS. Antiplatelet Premedication for Stent-Assisted Coil Embolization of Intracranial Aneurysms: Low-Dose Prasugrel vs Clopidogrel. Neurosurgery. 2018;83:981–8.CrossRefPubMed
22.
go back to reference Hvas AM, Favaloro EJ. Platelet Function Analyzed by Light Transmission Aggregometry. Methods Mol Biol. 2017;1646:321–31.CrossRefPubMed Hvas AM, Favaloro EJ. Platelet Function Analyzed by Light Transmission Aggregometry. Methods Mol Biol. 2017;1646:321–31.CrossRefPubMed
23.
go back to reference McTaggart RA, Choudhri OA, Marcellus ML, Brennan T, Steinberg GK, Dodd RL, Do HM, Marks MP. Use of thromboelastography to tailor dual-antiplatelet therapy in patients undergoing treatment of intracranial aneurysms with the Pipeline embolization device. J Neurointerv Surg. 2015;7:425–30.CrossRefPubMed McTaggart RA, Choudhri OA, Marcellus ML, Brennan T, Steinberg GK, Dodd RL, Do HM, Marks MP. Use of thromboelastography to tailor dual-antiplatelet therapy in patients undergoing treatment of intracranial aneurysms with the Pipeline embolization device. J Neurointerv Surg. 2015;7:425–30.CrossRefPubMed
24.
go back to reference Le Quellec S, Bordet JC, Negrier C, Dargaud Y. Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response. A review of the literature. Thromb Haemost. 2016;116:638–50.CrossRefPubMed Le Quellec S, Bordet JC, Negrier C, Dargaud Y. Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response. A review of the literature. Thromb Haemost. 2016;116:638–50.CrossRefPubMed
Metadata
Title
Dual Testing to Achieve Low On-treatment Platelet Reactivity for Aneurysm Embolization
Authors
Halitcan Batur
Mehmet A. Topcuoglu
Sinan Balci
Ethem M. Arsava
Anil Arat
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
Clinical Neuroradiology / Issue 4/2021
Print ISSN: 1869-1439
Electronic ISSN: 1869-1447
DOI
https://doi.org/10.1007/s00062-021-01011-7

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