Original Articles
14 July 2025
Early Access
Utility of the aspirin and P2Y12 response assays to determine the effects of antiplatelet agents in patients with subdural hematoma undergoing neurosurgery
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
336
Views
60
Downloads
Authors
Data on the use of reactivity tests in high-risk procedures derive mainly from cardiac surgery but could also have applicability in neurosurgery. Our study aims to evaluate the safety of reactivity tests in patients with surgical indications for chronic subdural hematoma (CSDH). We conducted a case-control study to determine risk factors and outcomes (early-onset complications if they occurred <7 days; late-onset if they occurred >7 days) in patients undergoing evacuation of CSDH recruited in the 2-year period 2022-2024. Patients with a history of antiplatelet treatment and reactivity test with early negativization (patients in whom the platelet aggregation test became negative before the required suspension period for safely performing the surgical intervention) and urgent neurosurgical indication were considered cases. Patients who were not taking antiplatelet therapy were considered controls. Complications taken into consideration were cerebral acute subdural hematoma, intraparenchymal hemorrhage, and ischemic complications. We analyzed data from 170 patients who consecutively underwent neurosurgical intervention for CSDH. We enrolled 68 cases who were on antiplatelet therapy before the procedure and showed early negativization on reactivity tests (cases) and 102 controls who were patients who had never been on antiplatelet therapy (controls). We did not observe statistically significant early-onset complications in the case group when compared to the control one (p: 0.64). Regarding late-onset complications, the incidence of total hemorrhagic events was similar in the two study groups (p: 0.14). CSDH is an extremely common condition in the elderly population and in patients on antiplatelet drugs. This condition often requires an urgent neurosurgical intervention, and waiting for antiplatelet treatment to be ineffective could worsen the outcome. Reactivity tests could therefore be a useful and safe tool to guide the timing of neurosurgery and to reduce the hospitalization time.
Altmetrics
Downloads
Download data is not yet available.
Citations
Stovell MG, Jenkinson MD. Neurosurgery in octogenarians. Br J Neurosurg 2014;28:611-5. DOI: https://doi.org/10.3109/02688697.2014.889809
Alvikas J, Zenati M, Campwala I, et al. Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study. J Trauma Acute Care Surg 2022;92:167-76. DOI: https://doi.org/10.1097/TA.0000000000003427
Stubbs DJ, Davies BM, Edlmann E, et al. Clinical practice guidelines for the care of patients with a chronic subdural haematoma: multidisciplinary recommendations from presentation to recovery. Br J Neurosurg 2024:1-10. DOI: https://doi.org/10.1101/2024.08.19.24312047
Feghali J, Yang W, Huang J. Updates in chronic subdural hematoma: epidemiology, etiology, pathogenesis, treatment and outcome. World Neurosurg 2020;141:339-45. DOI: https://doi.org/10.1016/j.wneu.2020.06.140
Mehta V, Harward SC, Sankey EW, et al. Evidence based diagnosis and management of chronic subdural hematoma: a review of the literature. J Clin Neurosci 2018;50:7-15. DOI: https://doi.org/10.1016/j.jocn.2018.01.050
Hamou HA, Clusmann H, Schulz JB, et al. Chronic subdural hematoma. Dtsch Arztebl Int 2022;119:208-13.
Pamukcu B. A review of aspirin resistance; definition, possible mechanisms, detection with platelet function tests, and its clinical outcomes. J Thromb Thrombolysis 2007;23:213-22. DOI: https://doi.org/10.1007/s11239-006-9043-2
Leunissen TC, Janssen PW, Ten Berg JM, et al. The use of platelet reactivity testing in patients on antiplatelet therapy for prediction of bleeding events after cardiac surgery. Vascul Pharmacol 2016;77:19-27. DOI: https://doi.org/10.1016/j.vph.2015.12.002
Mahla E, Tantry US, Prüller F, Gurbel PA. Is there a role for preoperative platelet function testing in patients undergoing cardiac surgery during antiplatelet therapy? Circulation 2018;138:2145-59. DOI: https://doi.org/10.1161/CIRCULATIONAHA.118.035160
Agarwal S. Platelet function testing in cardiac surgery. Transfus Med 2016;26:319-29. DOI: https://doi.org/10.1111/tme.12335
Galli M, Terracina S, Schiera E, et al. Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy: results from a large tertiary care hospital. J Thromb Thrombolysis 2025;58:71-83. DOI: https://doi.org/10.1007/s11239-024-03022-w
Angiolillo DJ, Suryadevara S, Capranzano P, et al. Antiplatelet drug response variability and the role of platelet function testing: a practical guide for interventional cardiologists. Catheter Cardiovasc Interv 2009;73:1-14. DOI: https://doi.org/10.1002/ccd.21782
Vila PM, Zafar MU, Badimon JJ. Platelet reactivity and nonresponse to dual antiplatelet therapy: a review. Platelets 2009;20:531-8. DOI: https://doi.org/10.3109/09537100903261379
Choi SY, Kim MH. Comparison of factors affecting platelet reactivity in various platelet function tests. Platelets 2019;30:631-6. DOI: https://doi.org/10.1080/09537104.2018.1499887
Gao H, Yang N, Yang L, et al. Advances and perspectives in methods for identifying high platelet reactivity. Heliyon 2023;9:e22214. DOI: https://doi.org/10.1016/j.heliyon.2023.e22214
Halvorsen S, Mehilli J, Cassese S, et al. 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J 2022;00:1-99. DOI: https://doi.org/10.1093/eurheartj/ehac270
Shlobin N, Kedda J, Wishart D, et al. Surgical management of chronic subdural hematoma in older adults: a systematic review. J Gerontol A Biol Sci Med Sci 2021;76:1454-62. DOI: https://doi.org/10.1093/gerona/glaa293
De Bonis P, Olei S, Mongardi L, et al. Chronic subdural hematoma in patients aged 80 years and older: a two-centre study. Clin Neurol Neurosurg 2018;170:88-92. DOI: https://doi.org/10.1016/j.clineuro.2018.05.002
Stippler M, Ramirez P, Berti A, et al. Chronic subdural hematoma patients aged 90 years and older. Neurol Res 2013;35:243-6. DOI: https://doi.org/10.1179/1743132813Y.0000000163
Torihashi, Sadamasa N, Yoshida K, et al. Independent predictors for recurrence of chronic subdural hematoma: a review of 343 consecutive surgical cases. Neurosurgery 2008;63:1125-9. DOI: https://doi.org/10.1227/01.NEU.0000335782.60059.17
Ducruet AF, Grobelny BT, Zacharia BE, et al. The surgical management of chronic subdural hematoma. Neurosurg Rev 2012;35:155-69. DOI: https://doi.org/10.1007/s10143-011-0349-y
Rohde V, Graf G, Hassler W, et al. Complications of burr-hole craniostomy and closed-system drainage for chronic subdural hematomas: a retrospective analysis of 376 patients. Neurosurg Rev 2002;25:89-94. DOI: https://doi.org/10.1007/s101430100182
Almenawer SA, Farrokhyar F, Hong C, et al. Chronic subdural hematoma management: a systematic review and meta-analysis of 34,829 patients. Ann Surg 2014;259:449-57. DOI: https://doi.org/10.1097/SLA.0000000000000255
Mori K, Maeda M. Surgical treatment of chronic subdural hematoma in 500 consecutive cases: clinical characteristics, surgical outcome, complications and recurrence rate. Neurol Med Chir 2001;41:371-81. DOI: https://doi.org/10.2176/nmc.41.371
Miah IP, Tank Y, Rosendaal FR, et al. Radiological prognostic factors of chronic subdural hematoma recurrence: a systematic review and meta-analysis. Neuroradiology 2021;63:27-40. DOI: https://doi.org/10.1007/s00234-020-02558-x
Lega BC, Danish SF, Malhotra NR, et al. Choosing the best operation for chronic subdural hematoma: a decision analysis. J Neurosurg 2010;113:615-21. DOI: https://doi.org/10.3171/2009.9.JNS08825
Bliden KP, Kundan P, Kraft D, et al. Utility of VerifyNow to assess the immediate pharmacodynamic response of chewed and swallowed aspirin: comparison with aggregometry. Platelets 2024;35:2298352. DOI: https://doi.org/10.1080/09537104.2023.2298352
Angiolillo DJ, Been L, Rubinstein M, et al. Use of the VerifyNow point of care assay to assess the pharmacodynamic effects of loading and maintenance dose regimens of prasugrel and ticagrelor. J Thromb Thrombolysis 2021;51:741-7. DOI: https://doi.org/10.1007/s11239-021-02386-7
Kakouros N, Kickler TS, Laws KM, Rade JJ. Hematocrit alters VerifyNow P2Y12 assay results independently of intrinsic platelet reactivity and clopidogrel responsiveness. J Thromb Haemost 2013;11:1814-22. DOI: https://doi.org/10.1111/jth.12376
Kim YG, Suh JW, Park JJ, et al. Different influences of hematocrit on the results of two Point‑Of‑Care platelet function tests, the VerifyNow assay and multiple electrode platelet aggregometry. PLoS One 2014;9:e114053. DOI: https://doi.org/10.1371/journal.pone.0114053
Kim YG, Suh JW, Sibbing D, et al. A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: a systematic review and meta‑analysis. Am Heart J 2017;188:53‑64. DOI: https://doi.org/10.1016/j.ahj.2017.03.006
Cuschieri S. The STROBE guidelines. Saudi J Anaesth 2019;13:S31-4. DOI: https://doi.org/10.4103/sja.SJA_543_18
Brar SS, ten Berg J, Marcucci R, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011;58:1945-54. DOI: https://doi.org/10.1016/j.jacc.2011.06.059
Schirmer CM, Bulsara KR, Al-Mufti F, et al. Antiplatelets and antithrombotics in neurointerventional procedures: Guideline update. J Neurointerv Surg 2023;15:1155-62. DOI: https://doi.org/10.1136/jnis-2022-019844
Kass-Hout T, Alderazi YJ, Amuluru K, et al. Neurointerventional stenting and antiplatelet function testing: to do or not to do? Intervent Neurol 2014;3:184-9. DOI: https://doi.org/10.1159/000431261
Kim KS, Fraser JF, Grupke S, et al. Management of antiplatelet therapy in patients undergoing neuroendovascular procedures. J Neurosurg 2018;129:890-905. DOI: https://doi.org/10.3171/2017.5.JNS162307
Fiorella D, Thiabolt L, Albuquerque FC, et al. Antiplatelet therapy in neuroendovascular therapeutics. Neurosurg Clin N Am 2005;16:517-40. DOI: https://doi.org/10.1016/j.nec.2005.03.003
Faught RWF, Satti SR, Hurst RW, et al. Heterogeneous practice patterns regarding 28antiplatelet medications for neuroendovascular stenting in the USA: a multicenter survey. J Neurointervent Surg 2014;6:774-9. DOI: https://doi.org/10.1136/neurintsurg-2013-010954
Hwang G, Huh W, Lee JS, et al. Standard vs modified antiplatelet preparation for preventing thromboembolic events in patients with high on-treatment platelet reactivity undergoing coil embolization for an unruptured intracranial aneurysm: a randomized clinical trial. JAMA Neurol 2015;72:764-72. DOI: https://doi.org/10.1001/jamaneurol.2015.0654
Yamada NK, Cross DT 3rd, Pilgram TK, et al. Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms. AJNR Am J Neuroradiol 2007;28:1778-82. DOI: https://doi.org/10.3174/ajnr.A0641
Oprea AD, Popescu WM. P2Y12 receptor inhibitors in acute coronary syndromes: what is new on the horizon? Cardiol Res Pract 2013;2013:195456. DOI: https://doi.org/10.1155/2013/195456
Yamaguchi Y, Abe T, Sato Y, et al. Effects of VerifyNow P2Y12 test and CYP2C19*2 testing on clinical outcomes of patients with cardiovascular disease: a systematic review and meta-analysis. Platelets 2013;24:352-61. DOI: https://doi.org/10.3109/09537104.2012.700969
Dahabreh IJ, Moorthy D, Lamont JL, et al. Testing of CYP2C19 variants and platelet reactivity for guiding antiplatelet treatment. Rockville, MD, USA: Agency for Healthcare Research and Quality; 2013.
Chan NC, Eikelboom JW, Ginsberg JS, et al. Role of phenotypic and genetic testing in managing clopidogrel therapy. Blood 2014;124:689-99. DOI: https://doi.org/10.1182/blood-2014-01-512723
Pereira NL, So D, Bae J-H, et al. International survey of patients undergoing percutaneous coronary intervention and their attitudes toward pharmacogenetic testing. Pharmacogenet Genomics 2019;29:76-83. DOI: https://doi.org/10.1097/FPC.0000000000000368
Javed K, Unda SR, Holland R, et al. Thromboelastography (TEG) results are predictive of ischemic and hemorrhagic complications in patients with unruptured intracranial aneurysms treated with flow diversion. Interv Neuroradiol 2022;28:219-28. DOI: https://doi.org/10.1177/15910199211025917
Igor CS, Mernes R, Lobotesis K, et al. Clopidogrel-related platelet inhibition: correlation with peri-operative adverse events in neurointerventional procedures. EJMINT 2014:1437000160.
Fifi JT, Brockington C, Narang J, et al. Clopidogrel resistance is associated with thromboembolic complications in patients undergoing neurovascular stenting. AJNR Am J Neuroradiol 2013;34:716-20. DOI: https://doi.org/10.3174/ajnr.A3405
Delgado Almandoz JE, Crandall BM, Scholz JM, et al. Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline embolization device. J NeuroIntervent Surg 2013;5:iii3-10. DOI: https://doi.org/10.1136/neurintsurg-2012-010582
Brinjikji W, Lanzino G, Cloft HJ, et al. Platelet testing is associated with worse clinical outcomes for patients treated with the Pipeline embolization device. AJNR Am J Neuroradiol 2015;36:2090-5. DOI: https://doi.org/10.3174/ajnr.A4411
Hanel RA, Kallmes DF, Lopes DK, et al. Prospective study on embolization of intracranial aneurysms with the Pipeline device: the PREMIER study 1 year results. J NeuroIntervent Surg 2020;12:62-6. DOI: https://doi.org/10.1136/neurintsurg-2019-015091
Katzman BM, Wockenfus AM, Scott RJ, et al. Estimating short- and long-term reference change values and index of individuality for tests of platelet function. Clin Biochem 2019;74:54-9. DOI: https://doi.org/10.1016/j.clinbiochem.2019.10.001
Lee DH, Kim HS, Kim SM, et al. Change of platelet reactivity to antiplatelet therapy after stenting procedure for cerebral artery stenosis: verifynow antiplatelet assay before and after stenting. Neurointervention 2012;7:23-6. DOI: https://doi.org/10.5469/neuroint.2012.7.1.23
Khanna V, Mikael R, Thayalasamy K, et al. Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease? J Thromb Haemost 2015;13:920-30. DOI: https://doi.org/10.1111/jth.12909
Tello-Montoliu A, Rivera J, Hernández D, et al. Temporal changes in platelet response in acute coronary syndrome patients with prasugrel and clopidogrel after stent implantation. Circ J 2018;82:353-60. DOI: https://doi.org/10.1253/circj.CJ-17-0471
Watanabe Y, Kozuma K, Ishikawa S, et al. Hyper-response to clopidogrel in Japanese patients undergoing transcatheter aortic valve implantation. Int Heart J 2016;57:190-7. DOI: https://doi.org/10.1536/ihj.15-290
Beynon C, Hertle DN, Unterberg AW, Sakowitz OW. Clinical review: traumatic brain injury in patients receiving antiplatelet medication. Crit Care 2012;16:228. DOI: https://doi.org/10.1186/cc11292
Bachelani AM, Bautz JT, Sperry JL, et al. Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury. Surgery 2011;150:836-43. DOI: https://doi.org/10.1016/j.surg.2011.07.059
Bansal V, Fortlage D, Lee J, et al. A new clopidogrel (Plavix) point-of-care assay: rapid determination of antiplatelet activity in trauma patients. J Trauma 2011;70:65-9. DOI: https://doi.org/10.1097/TA.0b013e318204fdae
Parry PV, Choi PA, Bauer JS, et al. Utility of the aspirin and P2Y12 response assays to determine the effect of antiplatelet agents on platelet reactivity in traumatic brain injury, Neurosurgery 2017;80:92-6. DOI: https://doi.org/10.1227/NEU.0000000000001406
Kamenova M, Mueller C, Coslovsky M, et al. Low-dose aspirin and burr-hole drainage of chronic subdural hematoma: study protocol for a randomized controlled study. Trials 2019;20:70. DOI: https://doi.org/10.1186/s13063-018-3064-y
Poon MTC, Rea C, Kolias AG, et al. Influence of antiplatelet and anticoagulant drug use on outcomes after chronic subdural hematoma drainage. J Neurotrauma 2021;38:1177-84. DOI: https://doi.org/10.1089/neu.2018.6080
Kerttula S, Huttunen J, Leinonen V, et al. The effect of antithrombotic therapy on the recurrence and outcome of chronic subdural hematoma after burr-hole craniostomy in a population-based cohort. Acta Neurochir 2022;164:2699-708. DOI: https://doi.org/10.1007/s00701-022-05337-0
How to Cite
Utility of the aspirin and P2Y12 response assays to determine the effects of antiplatelet agents in patients with subdural hematoma undergoing neurosurgery. (2025). Italian Journal of Medicine. https://doi.org/10.4081/itjm.2025.1926
Copyright (c) 2025 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- P. Bordin, C. Volpe, G. Anzil, R. Damato, C. Di Loreto, A swollen knee in a patient with refractory anaemia , Italian Journal of Medicine: Vol. 2 No. 4 (2008)
- G. Airoldi, M. Campanini, Fondaparinux , Italian Journal of Medicine: Vol. 2 No. 1 (2008)
- Franco Manzato, Massimo Franchini, Emergency management of patients being treated with oral anticoagulants , Italian Journal of Medicine: Vol. 7 No. 4 (2013)
- Sirio Fiorino, Andrea Carusi, Alessandro Zappi, Fabio Tateo, Luca Peruzzo, Melissa Zanardi, Francesco Savelli, Giulia Di Marzio, Silvia Cesaretti, Francesca Dazzani, Raffaella Francesconi , Paolo Leandri , Gianfranco Tortorici , Susanna Vicari , Dora Melucci, Federico Lari, Characteristics, comorbidities and laboratory measures associated with disease severity and poor prognosis in young and elderly patients with COVID-19 admitted to medical wards in Emilia-Romagna region, Italy: a multicentre retrospective study , Italian Journal of Medicine: Vol. 17 No. 1 (2023)
- Aigerim O. Murzakhmetova, Vitaly B. Kamkhen, Ayagul M. Ainabay, Assel M. Meiramova, Vadim M. Kemaykin, Bayan A. Ainabekova, Association of β2 microglobulin level and glomerular filtration rate in patients with acute leukemia after hematopoietic stem cell transplantation , Italian Journal of Medicine: Vol. 17 No. 1 (2023)
- Elena Garlatti Costa, Michela Ghersetti, Silvia Grazioli, Pietro Casarin, Efficacy of dual therapy in patients >65 years old with alanine transaminase flare during chronic hepatitis C genotype 2 , Italian Journal of Medicine: Vol. 9 No. 1 (2015)
- Ombretta Para, Lorenzo Caruso, Caterina Pestelli, Giulia Pestelli, Giacomo Fedi, Stefano Guidi, Alessia Abenante, Carlo Nozzoli, Prognostic factors for SARS-CoV-2 nasopharyngeal swab negativity: a multicentric study , Italian Journal of Medicine: Vol. 16 No. 1 (2022)
- Anna Rocci, Enrico Paganelli, Angelo Rossetti, Carla Marcato, Davide Martorana, Maria Ilaria Tassoni, Roberto Quintavalla, Multiple contemporary arterial dissection in Ehlers-Danlos syndrome type IV , Italian Journal of Medicine: Vol. 9 No. 1 (2015)
- Volkan Karakuş, Egemen Kaya, Yelda Dere, Fahri Åžahin, Different clinical courses with the same findings: two cases of paroxysmal nocturnal hemoglobinuria presenting with thrombocytopenia , Italian Journal of Medicine: Vol. 15 No. 3 (2021)
- Marta Maset, Elena Garlatti Costa, Giorgio Siro Carniello, Silvia Grazioli, Michela Ghersetti, Pietro Casarin, Fever and erythema: exclude all and then think of Still's disease! , Italian Journal of Medicine: Vol. 10 No. 3 (2016)
You may also start an advanced similarity search for this article.