Analysis of perioperative period coagulation function affected by antiepileptic drugs in epilepsy surgery

Analysis of perioperative period coagulation function affected by antiepileptic drugs in epilepsy surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analysis of perioperative period coagulation function affected by antiepileptic drugs in epilepsy surgery Yue Huang, Dejin Gao, Wanchen Dou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4312766/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Dec, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Drug-resistant epilepsy is a chronic condition that refers to epilepsy that does not improve with adequate medication treatment. For such cases, surgical intervention is a crucial strategy. However, in some patients, hemorrhage may occur after the operation. Proper management of antiepileptic drugs is essential for perioperative care in epilepsy surgery. It should be noted that certain antiepileptic drugs may negatively affect coagulation function. In this study, we aim to summarize the coagulation function of epilepsy patients during the perioperative period and compare the postoperative coagulation function when using sodium valproate and levetiracetam. Method Sixty-one epilepsy patients (age=30.79±10.30 years old; M:F=38:23) who underwent surgical treatments in Peking Union Medical College Hospital from April 2019 to April 2022 were enrolled in the study. Coagulation functions were evaluated using laboratory examination. Based on their perioperative medication, they were divided into two groups - sodium valproate and levetiracetam. We used t-test to measure the coagulation function parameters affected by the operation and then used independent t-test to determine the differences in coagulation function between the two groups. Result Abnormal PT, APTT, Fbg within 3 days after operation were found 84.8%, 28.3%, 93.5% respectively in patients using sodium valproate intravenous preparation, while these parameters are 26.7%, 26.7%, 26.7% respectively in patients using levetiracetam intravenous preparation. The patients who take sodium valproate intravenous preparation get higher value of PT increase in perioperative time compared to patient using levetiracetam intravenous preparation. Conclusion Patients with epilepsy are at risk of experiencing abnormal coagulation function following epilepsy surgery. It has been observed that patients may experience more severe and prolonged prothrombin time (PT) when using intravenous valproic acid preparation during the perioperative period, as compared to using levetiracetam intravenous preparation. These findings highlight the importance of monitoring coagulation function after epilepsy surgery. Surgeons should closely monitor patients who receive sodium valproate treatment during the perioperative period for any potential impact on their coagulation function post-surgery. epilepsy surgery perioperative management coagulation function Antiepileptic drugs Introduction Epilepsy is a chronic neurological disorder that results from various factors and causes recurrent, episodic, and temporary dysfunction of the central nervous system, defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition. It has a substantial impact on the quality of life and imposes a significant burden on society. Epilepsy accounts for 1% of the world's diseases[1], with more than 30% of cases being refractory to medication [2]. Drug-resistant epilepsy is defined as the failure of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom[3]. Surgical treatment provides the opportunity for drug-resistant epilepsy remission for patients with focal epilepsy whose seizures persist despite anti-epileptic medications[4]. With the advancement of related science and technology, several surgical treatment methods have emerged over the past few decades. Surgical treatment methods for epilepsy can be categorized into resective surgery, palliative surgery, neurostimulation, and other techniques. Among these methods, resective surgery for epileptogenic zone is the most common surgical strategy[5]. Although resective surgery has a satisfactory outcome, the possible complications need to be taken into consideration. The common postoperative complications include neurological deficits, wound infections, hemorrhage, and central nervous system infection. These complications may affect the clinical outcome and sometimes pose a threat to life. Previous studies have reported that the rate of postoperative hemorrhage ranges from 1.2% to 3.2%[6]. It has been observed that patients who undergo surgical treatment for epilepsy have a higher potential for abnormal coagulation function, which increases the risks for postoperative hemorrhage. It is important to provide antiepileptic treatment to control status epilepticus during the perioperative period. This requires the administration of intravenous AEDs to patients. However, there is currently a lack of literature on the coagulation function during the perioperative period of epilepsy surgery, particularly regarding AEDs management. Due to the medication procurement has changed in our hospital, the patients were treated by different intravenous AEDs. Therefore, we conducted a study to summarize the coagulation function during the perioperative period of epilepsy surgery and to determine whether the use of sodium valproate and levetiracetam during this period has a different effect on coagulation dysfunction. Method Samples This study was conducted in the Department of neurosurgery in the authors’ hospital between April 2019 and April 2022. A total of 61 patients diagnosed with drug-resistant epilepsy and performed surgical treatment were finally enrolled in this study. Inclusion criteria were:(1) diagnosed with drug-resistant epilepsy. (2) preoperative ASA classification gradeⅠorⅡ.(3) conduct epileptogenic zone resection or disconnection operation. Exclusion criteria were:(1) Preoperative anemia. (2) preoperative coagulation function abnormal. (3) never receive medication treatment. This study was approved by Ethics Committee in the author’s hospital. Procedures Patients diagnosed with drug-resistant epilepsy who are scheduled for epileptogenic zone resection or epileptogenic zone disconnection undergo routine pre-operative preparation, including laboratory examinations such as blood routine examination, coagulation function, and others. Afterward, the patients undergo craniotomy. Following the operation, we test their coagulation function, which includes prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB) concentration for three consecutive days. We record data, including sex, age, height, weight, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, disease etiology, surgery type, operative time, intraoperative blood loss, medication therapy, preoperative and postoperative values of hemoglobin (Hb), and postoperative complications to analyze the perioperative period coagulation function and baseline demographics. Patients are divided into two groups, sodium valproate group and levetiracetam group, based on their intravenous transfusion medication during and after the operation. In particular, patients in sodium valproate group were received intravenous sodium valproate for 0.4g at operative day and The first meal after operation; patients in levetiracetam group were received intravenous levetiracetam for 0.5g at operative day and The first meal after operation According to laboratory examination standards, we considered that PT above 12.6s, INR above 1.14, APTT above 32.5s, Fbg above 3.5g/L and Hgb below 110g/L as abnormal. We defined that post-operative PTmax as the maximum value of PT in 3 days after operation. We calculated POD1PT-Preoperative PT to measure the increase in prothrombin time after operation. Statistical Data were presented as ratio for classified variables and mean ±SD for continuous variables. One-sample Kolmogorov-Smirnov test was used to examine the normality of all data. The relationship of coagulation function between pre-operation and post-operation was evaluated by paired samples t-test. We count the amount and proportion of abnormal coagulation function subscale. Then, unpaired t-test were performed to identify the possible difference that affects abnormal coagulation function across the sodium valproate group and levetiracetam group. All the data were analyzed using IBM SPSS (version 22.0), and P< 0.05 was considered statistically significant. Results General characteristics A total of 61 patients (38 males and 23 females, age range: 13–67 y) were retrospectively reviewed. The patient demographics and general operative information were summarized in Table 1. Table 1 Patient Demographics Parameters Sodium valproate group (Mean±SE) Levetiracetam group(Mean±SE) p Total patients 46 15 Sex (male/female) 26/20 12/3 0.103 Age (y) 31.02(±1.62) 30.07(±2.10) 0.379 ASA classification(I/II) 43/3 13/2 0.404 epileptogenic zone (temporal lobe / frontal lobe / parietal lobe) 39/6/1 14/1/0 0.574 Hippocampal sclerosis 30(65.2%) 9(60.0%) 0.639 Surgery type (resection/disconnection) 18/28 8/7 0.341 Chronic AEDs treatment before operation (0/1/2/3) 2/14/18/9 0/3/7/4 0.823 Height (cm) 168.35(±8.15) 170.80(±6.43) 0.147 Weight (kg) 65.72(±9.88) 70.80(±15.69) 0.143 BMI (kg/m 2 ) 23.18(±3.11) 24.14(±4.64) 0.184 Operative time (h) 4.98(±0.16) 5.33(±0.15) 0.111 Blood loss in surgery (ml) 205.87(±14.38) 196.67(±14.20) 0.365 Perioperative coagulation function summary In this study, it was observed that patients had normal coagulation function and hemoglobin levels before undergoing surgical treatment. However, after the operation, there was a significant change in the coagulation function. On the first day after the operation, abnormal PT (Prothrombin Time), APTT (Activated Partial Thromboplastin Time), and Fbg (Fibrinogen) were found in 60.9%, 15.2%, and 17.4% respectively in the Sodium Valproate group. On the other hand, in the Levetiracetam group, these abnormalities were found in 26.7% of patients for each measurement. Additionally, a higher percentage of patients (84.8%) who took Sodium Valproate medication during the perioperative period had confirmed abnormal PT within three days after the operation as compared to those who took levetiracetam. Table 2 shows the details of these findings. Table 2 perioperative coagulation function Perioperative coagulation function in Sodium valproate group(n=46) Preoperative Mean(±SD) Postoperative Mean(±SD) Abnormal N(%) p value PT 11.89(±0.62) Postoperative day 1 13.03(±0.98) 28(60.9%) 0.00 Postoperative max 13.90(±1.20) 39(84.8%) 0.00 INR 1.01(±0.07) Postoperative day 1 1.11(±0.09) 15(32.6%) 0.00 Postoperative max 1.18(±0.11) 25(54.3%) 0.00 APTT 27.64(±2.46) Postoperative day 1 26.04(±2.97) 7(15.2%) 0.00 Postoperative max 30.04(±3.80) 13(28.3%) 0.00 FBG 2.22(±0.55) Postoperative day 1 2.57(±0.63) 8(17.4%) 0.00 Postoperative max 5.80(±1.55) 43(93.5%) 0.00 HGB 138.59(±14.87) Postoperative day 1 122.24(±15.25) 12(26.1%) 0.00 Postoperative min 109.57 (±15.20) 32(69.6%) 0.00 Perioperative coagulation function in Levetiracetam group (n=15) Preoperative Mean(±SD) Postoperative Mean(±SD) Abnormal N(%) p value PT(s) 11.60(±0.67) Postoperative day 1 12.34(±0.91) 4(26.7%) 0.00 Postoperative max 14.11(±1.10) 7(46.7%) 0.00 INR 0.99(±0.06) Postoperative day 1 1.08(±0.06) 1(6.7%) 0.00 Postoperative max 1.23(±0.09) 11(73.3%) 0.00 APTT(s) 27.22(±2.22) Postoperative day 1 25.57(±3.30) 4(26.7%) 0.06 Postoperative max 30.68(±3.17) 4(26.7%) 0.00 FBG(g/L) 2.13(±0.31) Postoperative day 1 2.52(±1.19) 4(26.7%) 0.10 Postoperative max 6.47(±1.23) 15(100%) 0.00 HGB(g/L) 143.07 (±11.73) Postoperative day 1 123.33(±13.73) 6(40.0%) 0.00 Postoperative min 107.33(±16.31) 12(80.0%) 0.00 *Value in bold indicates statistical significance. Postoperative prothrombin time analysis The coagulation process is divided into two pathways: one activated by tissue factor (PT), and the other activated by the contact pathway (APTT). These pathways are linked by the production of thrombin by the prothrombinase complex and the conversion of fibrinogen to fibrin by thrombin. The prothrombin time (PT) is the most commonly used coagulation test in clinical laboratories. It can evaluate the tissue factor (TF) and common coagulation pathways affected by the activity of coagulation factors II (FII), V (FV), VII (FVII), X (FX), and fibrinogen[7]. The PT assesses the initiation of hemostasis [8]. Research has shown that prolonged PT is not uncommon during the perioperative period [9]. In our study, a significant proportion of epileptic patients experienced abnormal PT within three days after surgery. We used a t-test to determine if perioperative antiepileptic medication affected prolonged PT. Patients who took levetiracetam during the perioperative period had better results than those who used sodium valproate. Both groups experienced prolonged PT, but the increase in PT after surgery was significantly higher in the sodium valproate group. This information is detailed in Table 3. After the operation, two patients in the sodium valproate group developed intracranial hemorrhage and required unplanned resurgery to treat the bleeding. None of patient developed intracranial hemorrhage in levetiracetam group. Table 3 perioperative PT analysis between groups Preoperative laboratorial examination Sodium valproate group（n=46） Levetiracetam group (n=15) P Preoperative PT(s) 11.89(±0.09) 11.61(±0.17) 0.070 POD1 PT(s) 13.03(±0.15) 12.33(±0.23) 0.009* POD1PT-Preoperative PT(s) 1.14(±0.12) 0.72(±0.19) 0.040* PTmax(s) 13.90(±0.18) 14.11(±0.28) 0.268 Preoperative INR 1.01(±0.01) 0.98(±0.02) 0.156 POD1 INR 1.11(±0.01) 1.07(±0.02) 0.112 POD1INR-Preoperative INR 0.10(±0.01) 0.09(±0.01) 0.293 INRmax(s) 1.18(±0.02) 1.23(±0.02) 0.093 Preoperative APTT(s) 27.64(±0.36) 27.22(±0.57) 0.280 POD1 APTT(s) 26.04(±0.44) 25.57(±0.85) 0.302 POD1 APTT-Preoperative APTT(s) -1.60(±0.45) -1.65(±0.81) 0.477 APTTmax(s) 30.03(±0.56) 30.68(±0.82) 0.276 Preoperative Fibrinogen(g/L) 2.22(±0.08) 2.13(±0.08) 0.275 POD1 Fibrinogen(g/L) 2.57(±0.09) 2.52(±0.31) 0.415 Fibrinogen max(g/L) 5.80(±0.23) 6.47(±0.32) 0.065 *Value in bold indicates statistical significance. POD1 refer to the first day after operation. Max means that the highest value within 3 days after operation. Discussion In this study, it was found that patients' coagulation function changes after surgery compared to their pre-operative state. Epilepsy patients, in particular, tend to have prolonged prothrombin time after surgery, which increases their risk of postoperative bleeding. This study has revealed that abnormal blood clotting is common in epilepsy surgery patients. Surgeons should closely monitor post-operative coagulation function and intervene when necessary. The coagulation dysfunction mainly affects the extrinsic coagulation pathway in epilepsy patients. Levetiracetam binds to synaptic vesicle protein SV2A, interfering with the release of the neurotransmitter stored within the vesicle[10]. It is a commonly used first-line choice for seizures in palliative care[11]. Previous studies have found that levetiracetam does not appear to cause clinically significant or relevant hematological adverse events suggestive of underlying hematological disorders [12]. Valproic acid (2-propyl pentanoic acid) is a first-line medication used for the treatment of epilepsy and bipolar disorder[13]. Advanced studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Previous studies proved that valproic acid might negatively affect coagulation function, especially for patients with chronic drug administration [12, 14]. However, a drug's acute and chronic administration are entirely different circumstances [15]. It is controversial for surgeons to ban valproate treatment before surgery. Studies did not show an increase in blood loss during craniotomy surgery in patients receiving preoperative valproate[16]. Our study focus on perioperative management. We find that compared to using levetiracetam intravenous preparation, using valproic acid intravenous preparation has more tendency to perform prolonged PT in the short term. Conclusion The current study indicated that epilepsy patients are likely to suffer from abnormal coagulation function after epilepsy surgery. In particular, abnormal PT after operation is quite common in epilepsy patients. Patients suffer from more serious prolonged PT when using valproic acid intravenous preparation during perioperative time than using levetiracetam intravenous preparation. Declarations Data Availability used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding No funds were received in support of this work. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions All authors made substantive intellectual contributions to this study to qualify as authors. YH and DJ contributed to acquisition of data, analysis of data, statistical analysis, and interpretation of results. YH and WC contributed to study design, study coordination, and manuscript preparation. All authors read and approved the final manuscript. Ethics approval and consent to participate Patient data were anonymous, and we analyzed previously collected data. Therefore, informed consent was not necessary. Our research was exempted from the Clinical Research Ethics Committee of Peking Union Medical College Hospital. Declarations of interest The authors have no relevant financial or nonfinancial interests to disclose.Consent for publication Not applicable. Acknowledgements Not applicable. References Tian N, Kobau R, Zack MM, Greenlund KJ. Barriers to and Disparities in Access to Health Care Among Adults Aged ≥ 18 Years with Epilepsy - United States, 2015 and 2017. MMWR Morbidity Mortal Wkly Rep. 2022;71(21):697–702. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314–9. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–77. Rugg-Gunn F, Miserocchi A, McEvoy A. Epilepsy surgery. Pract Neurol. 2020;20(1):4–14. Galan FN, Beier AD, Sheth RD. Advances in Epilepsy Surgery. Pediatr Neurol. 2021;122:89–97. Tebo CC, Evins AI, Christos PJ, Kwon J, Schwartz TH. Evolution of cranial epilepsy surgery complication rates: a 32-year systematic review and meta-analysis. J Neurosurg. 2014;120(6):1415–27. Dorgalaleh A, Daneshi M, Rashidpanah J, Roshani Yasaghi E. An overview of hemostasis. Congenital Bleeding Disorders 2018:3–26. Loizou E, Mayhew DJ, Martlew V, Murthy BVS. Implications of deranged activated partial thromboplastin time for anaesthesia and surgery. Anaesthesia. 2018;73(12):1557–63. Benzon HT, Park M, McCarthy RJ, Kendall MC, Lindholm PF. Mixing Studies in Patients With Prolonged Activated Partial Thromboplastin Time or Prothrombin Time. Anesth Analg. 2019;128(6):1089–96. Klitgaard H, Matagne A, Nicolas JM, Gillard M, Lamberty Y, De Ryck M, Kaminski RM, Leclercq K, Niespodziany I, Wolff C, et al. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016;57(4):538–48. Howard P, Remi J, Remi C, Charlesworth S, Whalley H, Bhatia R, Hitchens M, Mihalyo M, Wilcock A. Levetiracetam. J Pain Symptom Manag. 2018;56(4):645–9. Boon P, Hulhoven R, Offner F. Levetiracetam and bleeding disorders. Acta Neurol Belgica. 2007;107(4):97–102. Kostrouchová M, Kostrouch Z, Kostrouchová M. Valproic acid, a molecular lead to multiple regulatory pathways. Folia Biol (Praha). 2007;53(2):37–49. Gidal B, Spencer N, Maly M, Pitterle M, Williams E, Collins M, Jones J. Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration. Neurology. 1994;44(8):1418–22. Veinot JP, Ruel M. Valproic acid and bleeding: caution required. Ann Thorac Surg. 2007;83(2):725. author reply 725–726. Ward MM, Barbaro NM, Laxer KD, Rampil IJ. Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia. 1996;37(1):98–101. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Dec, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 03 May, 2024 Submission checks completed at journal 30 Apr, 2024 Editor assigned by journal 30 Apr, 2024 First submitted to journal 23 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4312766","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298335848,"identity":"52eee4c0-a280-4d2a-b32a-937b3b42ac32","order_by":0,"name":"Yue Huang","email":"","orcid":"","institution":"Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Huang","suffix":""},{"id":298335849,"identity":"8f8e69f6-d8e4-4b27-8fa7-8e6eec4059fc","order_by":1,"name":"Dejin Gao","email":"","orcid":"","institution":"Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Dejin","middleName":"","lastName":"Gao","suffix":""},{"id":298335850,"identity":"ecefbcff-9b26-4e08-9b19-970995945573","order_by":2,"name":"Wanchen Dou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYDCCAxAqgYGB+cCBDxWkaWFLPDjjDGlaeIwP87YQoYPveI+ZxM8ddnn80j0fDvA2MMjzix3Ar0XyzBkzyd4zycWSc85uOCC5g8Fw5uwE/FoMbuSY3eBtO5C44UbuhgOGZxgSDG4ToeXmX6CW/TdyHhxIbCNSy22wLRI5DAcOEqNF8syx8t+ybcmJM26kGRxsOCNB2C98x5s3G75ts0vsn5H8+POfCht5fmkCWtCBBGnKR8EoGAWjYBRgBwDTxk/Wa8H8SQAAAABJRU5ErkJggg==","orcid":"","institution":"Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Wanchen","middleName":"","lastName":"Dou","suffix":""}],"badges":[],"createdAt":"2024-04-23 14:44:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4312766/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4312766/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-03485-1","type":"published","date":"2025-12-18T15:58:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":98813996,"identity":"8e478a17-9e59-4e88-b719-56273dae225d","added_by":"auto","created_at":"2025-12-22 16:09:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":432269,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4312766/v1/82da1b8e-22bf-4479-9bf4-d45f4ea39162.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of perioperative period coagulation function affected by antiepileptic drugs in epilepsy surgery","fulltext":[{"header":"Introduction","content":"Epilepsy is a chronic neurological disorder that results from various factors and causes recurrent, episodic, and temporary dysfunction of the central nervous system, defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition. It has a substantial impact on the quality of life and imposes a significant burden on society. Epilepsy accounts for 1% of the world's diseases[1], with more than 30% of cases being refractory to medication [2]. Drug-resistant epilepsy is defined as the failure of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom[3]. Surgical treatment provides the opportunity for drug-resistant epilepsy remission for patients with focal epilepsy whose seizures persist despite anti-epileptic medications[4]. With the advancement of related science and technology, several surgical treatment methods have emerged over the past few decades. Surgical treatment methods for epilepsy can be categorized into resective surgery, palliative surgery, neurostimulation, and other techniques. Among these methods, resective surgery for epileptogenic zone is the most common surgical strategy[5]. Although resective surgery has a satisfactory outcome, the possible complications need to be taken into consideration. The common postoperative complications include neurological deficits, wound infections, hemorrhage, and central nervous system infection. These complications may affect the clinical outcome and sometimes pose a threat to life. Previous studies have reported that the rate of postoperative hemorrhage ranges from 1.2% to 3.2%[6]. It has been observed that patients who undergo surgical treatment for epilepsy have a higher potential for abnormal coagulation function, which increases the risks for postoperative hemorrhage. It is important to provide antiepileptic treatment to control status epilepticus during the perioperative period. This requires the administration of intravenous AEDs to patients. However, there is currently a lack of literature on the coagulation function during the perioperative period of epilepsy surgery, particularly regarding AEDs management. Due to the medication procurement has changed in our hospital, the patients were treated by different intravenous AEDs. Therefore, we conducted a study to summarize the coagulation function during the perioperative period of epilepsy surgery and to determine whether the use of sodium valproate and levetiracetam during this period has a different effect on coagulation dysfunction. "},{"header":"Method","content":"\u003cp\u003eSamples\u003c/p\u003e\n\u003cp\u003eThis study was conducted in the Department of neurosurgery in the authors\u0026rsquo; hospital between April 2019 and April 2022. A total of 61 patients diagnosed with drug-resistant epilepsy and performed surgical treatment were finally enrolled in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInclusion criteria were:(1) diagnosed with drug-resistant epilepsy. (2) preoperative ASA classification gradeⅠorⅡ.(3) conduct epileptogenic zone resection or disconnection operation. Exclusion criteria were:(1) Preoperative anemia. (2) preoperative coagulation function abnormal. (3) never receive medication treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was approved by Ethics Committee in the author\u0026rsquo;s hospital.\u003c/p\u003e\n\u003cp\u003eProcedures\u003c/p\u003e\n\u003cp\u003ePatients diagnosed with drug-resistant epilepsy who are scheduled for epileptogenic zone resection or epileptogenic zone disconnection undergo routine pre-operative preparation, including laboratory examinations such as blood routine examination, coagulation function, and others. Afterward, the patients undergo craniotomy. Following the operation, we test their coagulation function, which includes prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB) concentration for three consecutive days. We record data, including sex, age, height, weight, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, disease etiology, surgery type, operative time, intraoperative blood loss, medication therapy, preoperative and postoperative values of hemoglobin (Hb), and postoperative complications to analyze the perioperative period coagulation function and baseline demographics. Patients are divided into two groups, sodium valproate group and levetiracetam group, based on their intravenous transfusion medication during and after the operation. In particular, patients in sodium valproate group were received intravenous sodium valproate for 0.4g at operative day and\u0026nbsp;The first meal after operation; patients in levetiracetam group were received intravenous levetiracetam for 0.5g at operative day and\u0026nbsp;The first meal after operation\u003c/p\u003e\n\u003cp\u003eAccording to laboratory examination standards, we considered that PT above 12.6s, INR above 1.14, APTT above 32.5s, Fbg above 3.5g/L and Hgb below 110g/L as abnormal. We defined that post-operative PTmax as the maximum value of PT in 3 days after operation. We calculated POD1PT-Preoperative PT to measure the increase in prothrombin time after operation.\u003c/p\u003e\n\u003cp\u003eStatistical\u003c/p\u003e\n\u003cp\u003eData were presented as ratio for classified variables and mean \u0026plusmn;SD for continuous variables. One-sample Kolmogorov-Smirnov test was used to examine the normality of all data. The relationship of coagulation function between pre-operation and post-operation was evaluated by paired samples t-test. We count the amount and proportion of abnormal coagulation function subscale. Then, unpaired t-test were performed to identify the possible difference that affects abnormal coagulation function across the sodium valproate group and levetiracetam group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the data were analyzed using IBM SPSS (version 22.0), and P\u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eGeneral characteristics\u003c/p\u003e\n\u003cp\u003eA total of 61 patients (38 males and 23 females, age range: 13\u0026ndash;67 y) were retrospectively reviewed. The patient demographics and general operative information were summarized in Table 1.\u003c/p\u003e\n\u003cp\u003eTable 1 Patient Demographics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003eSodium valproate group (Mean\u0026plusmn;SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003eLevetiracetam group(Mean\u0026plusmn;SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eTotal patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eSex (male/female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e26/20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e12/3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eAge (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e31.02(\u0026plusmn;1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e30.07(\u0026plusmn;2.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eASA classification(I/II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e43/3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e13/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.404\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eepileptogenic zone\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(temporal lobe / frontal lobe / parietal lobe)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39/6/1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14/1/0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eHippocampal sclerosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e30(65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e9(60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.639\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eSurgery type\u003c/p\u003e\n \u003cp\u003e(resection/disconnection)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18/28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8/7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eChronic AEDs treatment before operation\u003c/p\u003e\n \u003cp\u003e(0/1/2/3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e2/14/18/9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e0/3/7/4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e168.35(\u0026plusmn;8.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e170.80(\u0026plusmn;6.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e65.72(\u0026plusmn;9.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e70.80(\u0026plusmn;15.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e23.18(\u0026plusmn;3.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e24.14(\u0026plusmn;4.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eOperative time (h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e4.98(\u0026plusmn;0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e5.33(\u0026plusmn;0.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.98916967509025%\" valign=\"top\"\u003e\n \u003cp\u003eBlood loss in surgery (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.9927797833935%\" valign=\"top\"\u003e\n \u003cp\u003e205.87(\u0026plusmn;14.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.021660649819495%\" valign=\"top\"\u003e\n \u003cp\u003e196.67(\u0026plusmn;14.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePerioperative coagulation function summary\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; In this study, it was observed that patients had normal coagulation function and hemoglobin levels before undergoing surgical treatment. However, after the operation, there was a significant change in the coagulation function. On the first day after the operation, abnormal PT (Prothrombin Time), APTT (Activated Partial Thromboplastin Time), and Fbg (Fibrinogen) were found in 60.9%, 15.2%, and 17.4% respectively in the Sodium Valproate group. On the other hand, in the Levetiracetam group, these abnormalities were found in 26.7% of patients for each measurement. Additionally, a higher percentage of patients (84.8%) who took Sodium Valproate medication during the perioperative period had confirmed abnormal PT within three days after the operation as compared to those who took levetiracetam. Table 2 shows the details of these findings.\u003c/p\u003e\n\u003cp\u003eTable 2 perioperative coagulation function\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ePerioperative coagulation function in Sodium valproate group(n=46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.840579710144926%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003cp\u003eMean(\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.84057971014493%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative\u003c/p\u003e\n \u003cp\u003eMean(\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.86231884057971%\" valign=\"top\"\u003e\n \u003cp\u003eAbnormal\u003c/p\u003e\n \u003cp\u003eN(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.956521739130435%\" valign=\"top\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e11.89(\u0026plusmn;0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e13.03(\u0026plusmn;0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e28(60.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e13.90(\u0026plusmn;1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e39(84.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" valign=\"top\"\u003e\n \u003cp\u003eINR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" valign=\"top\"\u003e\n \u003cp\u003e1.01(\u0026plusmn;0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e1.11(\u0026plusmn;0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e15(32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e1.18(\u0026plusmn;0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e25(54.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAPTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e27.64(\u0026plusmn;2.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e26.04(\u0026plusmn;2.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e7(15.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e30.04(\u0026plusmn;3.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e13(28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eFBG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.22(\u0026plusmn;0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e2.57(\u0026plusmn;0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e8(17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e5.80(\u0026plusmn;1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e43(93.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHGB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e138.59(\u0026plusmn;14.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e122.24(\u0026plusmn;15.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e12(26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e109.57 (\u0026plusmn;15.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e32(69.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ePerioperative coagulation function in Levetiracetam group (n=15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.840579710144926%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003cp\u003eMean(\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.84057971014493%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative\u003c/p\u003e\n \u003cp\u003eMean(\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.86231884057971%\" valign=\"top\"\u003e\n \u003cp\u003eAbnormal\u003c/p\u003e\n \u003cp\u003eN(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.956521739130435%\" valign=\"top\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e11.60(\u0026plusmn;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e12.34(\u0026plusmn;0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e4(26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e14.11(\u0026plusmn;1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e7(46.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" valign=\"top\"\u003e\n \u003cp\u003eINR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" valign=\"top\"\u003e\n \u003cp\u003e0.99(\u0026plusmn;0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e1.08(\u0026plusmn;0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e1(6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e1.23(\u0026plusmn;0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e11(73.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAPTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e27.22(\u0026plusmn;2.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e25.57(\u0026plusmn;3.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e4(26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e30.68(\u0026plusmn;3.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e4(26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eFBG(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.13(\u0026plusmn;0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e2.52(\u0026plusmn;1.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e4(26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative max\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e6.47(\u0026plusmn;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e15(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.47739602169982%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHGB(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.806509945750452%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e143.07\u003c/p\u003e\n \u003cp\u003e(\u0026plusmn;11.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.412296564195298%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.529837251356238%\" valign=\"top\"\u003e\n \u003cp\u003e123.33(\u0026plusmn;13.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.839059674502712%\" valign=\"top\"\u003e\n \u003cp\u003e6(40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.934900542495479%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.526315789473685%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e107.33(\u0026plusmn;16.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.68421052631579%\" valign=\"top\"\u003e\n \u003cp\u003e12(80.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Value in bold indicates statistical significance.\u003c/p\u003e\n\u003cp\u003ePostoperative prothrombin time analysis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; The coagulation process is divided into two pathways: one activated by tissue factor (PT), and the other activated by the contact pathway (APTT). These pathways are linked by the production of thrombin by the prothrombinase complex and the conversion of fibrinogen to fibrin by thrombin. The prothrombin time (PT) is the most commonly used coagulation test in clinical laboratories. It can evaluate the tissue factor (TF) and common coagulation pathways affected by the activity of coagulation factors II (FII), V (FV), VII (FVII), X (FX), and fibrinogen[7]. The PT assesses the initiation of hemostasis\u0026nbsp;[8]. Research has shown that prolonged PT is not uncommon during the perioperative period\u0026nbsp;[9]. In our study, a significant proportion of epileptic patients experienced abnormal PT within three days after surgery. We used a t-test to determine if perioperative antiepileptic medication affected prolonged PT. Patients who took levetiracetam during the perioperative period had better results than those who used sodium valproate. Both groups experienced prolonged PT, but the increase in PT after surgery was significantly higher in the sodium valproate group. This information is detailed in Table 3. After the operation, two patients in the sodium valproate group developed intracranial hemorrhage and required unplanned resurgery to treat the bleeding. None of patient developed intracranial hemorrhage in levetiracetam group.\u003c/p\u003e\n\u003cp\u003eTable 3 perioperative PT analysis between groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative laboratorial examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003eSodium valproate group（n=46）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003eLevetiracetam group (n=15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative PT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e11.89(\u0026plusmn;0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e11.61(\u0026plusmn;0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1 PT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e13.03(\u0026plusmn;0.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e12.33(\u0026plusmn;0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1PT-Preoperative PT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e1.14(\u0026plusmn;0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e0.72(\u0026plusmn;0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.040*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePTmax(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e13.90(\u0026plusmn;0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e14.11(\u0026plusmn;0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative INR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e1.01(\u0026plusmn;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e0.98(\u0026plusmn;0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1 INR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e1.11(\u0026plusmn;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e1.07(\u0026plusmn;0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1INR-Preoperative INR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e0.10(\u0026plusmn;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e0.09(\u0026plusmn;0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003eINRmax(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e1.18(\u0026plusmn;0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e1.23(\u0026plusmn;0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative APTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e27.64(\u0026plusmn;0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e27.22(\u0026plusmn;0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1 APTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e26.04(\u0026plusmn;0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e25.57(\u0026plusmn;0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.302\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1 APTT-Preoperative APTT(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e-1.60(\u0026plusmn;0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e-1.65(\u0026plusmn;0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.477\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003eAPTTmax(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e30.03(\u0026plusmn;0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e30.68(\u0026plusmn;0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative Fibrinogen(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e2.22(\u0026plusmn;0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e2.13(\u0026plusmn;0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.275\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003ePOD1 Fibrinogen(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e2.57(\u0026plusmn;0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e2.52(\u0026plusmn;0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.415\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.19547657512116%\" valign=\"top\"\u003e\n \u003cp\u003eFibrinogen max(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.463651050080774%\" valign=\"top\"\u003e\n \u003cp\u003e5.80(\u0026plusmn;0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.455573505654282%\" valign=\"top\"\u003e\n \u003cp\u003e6.47(\u0026plusmn;0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.88529886914378%\" valign=\"top\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Value in bold indicates statistical significance.\u003c/p\u003e\n\u003cp\u003ePOD1 refer to the first day after operation.\u003c/p\u003e\n\u003cp\u003eMax means that the highest value within 3 days after operation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, it was found that patients\u0026apos; coagulation function changes after surgery compared to their pre-operative state. Epilepsy patients, in particular, tend to have prolonged prothrombin time after surgery, which increases their risk of postoperative bleeding.\u003c/p\u003e\n\u003cp\u003eThis study has revealed that abnormal blood clotting is common in epilepsy surgery patients. Surgeons should closely monitor post-operative coagulation function and intervene when necessary. The coagulation dysfunction mainly affects the extrinsic coagulation pathway in epilepsy patients.\u003c/p\u003e\n\u003cp\u003eLevetiracetam binds to synaptic vesicle protein SV2A, interfering with the release of the neurotransmitter stored within the vesicle[10]. It is a commonly used first-line choice for seizures in palliative care[11]. Previous studies have found that levetiracetam does not appear to cause clinically significant or relevant hematological adverse events suggestive of underlying hematological disorders [12].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Valproic acid (2-propyl pentanoic acid) is a first-line medication used for the treatment of epilepsy and bipolar disorder[13]. Advanced studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Previous studies proved that valproic acid might negatively affect coagulation function, especially for patients with chronic drug administration [12, 14]. However, a drug\u0026apos;s acute and chronic administration are entirely different circumstances [15]. It is controversial for surgeons to ban valproate treatment before surgery. Studies did not show an increase in blood loss during craniotomy surgery in patients receiving preoperative valproate[16]. Our study focus on perioperative management. We find that compared to using levetiracetam intravenous preparation, using valproic acid intravenous preparation has more tendency to perform prolonged PT in the short term.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe current study indicated that epilepsy patients are likely to suffer from abnormal coagulation function after epilepsy surgery. In particular, abnormal PT after operation is quite common in epilepsy patients. Patients suffer from more serious prolonged PT when using valproic acid intravenous preparation during perioperative time than using levetiracetam intravenous preparation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eData Availability\u003c/p\u003e\n\u003cp\u003eused and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo funds were received in support of this work.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eAll authors made substantive intellectual contributions to this study to qualify as authors. YH and DJ contributed to acquisition of data, analysis of data, statistical analysis, and interpretation of results. YH and WC contributed to study design, study coordination, and manuscript preparation. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003ePatient data were anonymous, and we analyzed previously collected data. Therefore, informed consent was not necessary. Our research was exempted from the Clinical Research Ethics Committee of Peking Union Medical College Hospital.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDeclarations of interest\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or nonfinancial interests to disclose.Consent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTian N, Kobau R, Zack MM, Greenlund KJ. Barriers to and Disparities in Access to Health Care Among Adults Aged\u0026thinsp;\u0026ge;\u0026thinsp;18 Years with Epilepsy - United States, 2015 and 2017. MMWR Morbidity Mortal Wkly Rep. 2022;71(21):697\u0026ndash;702.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Mosh\u0026eacute; SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRugg-Gunn F, Miserocchi A, McEvoy A. Epilepsy surgery. Pract Neurol. 2020;20(1):4\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalan FN, Beier AD, Sheth RD. Advances in Epilepsy Surgery. Pediatr Neurol. 2021;122:89\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTebo CC, Evins AI, Christos PJ, Kwon J, Schwartz TH. Evolution of cranial epilepsy surgery complication rates: a 32-year systematic review and meta-analysis. J Neurosurg. 2014;120(6):1415\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorgalaleh A, Daneshi M, Rashidpanah J, Roshani Yasaghi E. An overview of hemostasis. Congenital Bleeding Disorders 2018:3\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoizou E, Mayhew DJ, Martlew V, Murthy BVS. Implications of deranged activated partial thromboplastin time for anaesthesia and surgery. Anaesthesia. 2018;73(12):1557\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenzon HT, Park M, McCarthy RJ, Kendall MC, Lindholm PF. Mixing Studies in Patients With Prolonged Activated Partial Thromboplastin Time or Prothrombin Time. Anesth Analg. 2019;128(6):1089\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlitgaard H, Matagne A, Nicolas JM, Gillard M, Lamberty Y, De Ryck M, Kaminski RM, Leclercq K, Niespodziany I, Wolff C, et al. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016;57(4):538\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoward P, Remi J, Remi C, Charlesworth S, Whalley H, Bhatia R, Hitchens M, Mihalyo M, Wilcock A. Levetiracetam. J Pain Symptom Manag. 2018;56(4):645\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoon P, Hulhoven R, Offner F. Levetiracetam and bleeding disorders. Acta Neurol Belgica. 2007;107(4):97\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKostrouchov\u0026aacute; M, Kostrouch Z, Kostrouchov\u0026aacute; M. Valproic acid, a molecular lead to multiple regulatory pathways. Folia Biol (Praha). 2007;53(2):37\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGidal B, Spencer N, Maly M, Pitterle M, Williams E, Collins M, Jones J. Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration. Neurology. 1994;44(8):1418\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVeinot JP, Ruel M. Valproic acid and bleeding: caution required. Ann Thorac Surg. 2007;83(2):725. author reply 725\u0026ndash;726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWard MM, Barbaro NM, Laxer KD, Rampil IJ. Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia. 1996;37(1):98\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"epilepsy surgery, perioperative management, coagulation function, Antiepileptic drugs","lastPublishedDoi":"10.21203/rs.3.rs-4312766/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4312766/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eDrug-resistant epilepsy is a chronic condition that refers to epilepsy that does not improve with adequate medication treatment. For such cases, surgical intervention is a crucial strategy. However, in some patients, hemorrhage may occur after the operation. Proper management of antiepileptic drugs is essential for perioperative care in epilepsy surgery. It should be noted that certain antiepileptic drugs may negatively affect coagulation function. In this study, we aim to summarize the coagulation function of epilepsy patients during the perioperative period and compare the postoperative coagulation function when using sodium valproate and levetiracetam.\u003c/p\u003e\n\u003cp\u003eMethod\u003c/p\u003e\n\u003cp\u003eSixty-one epilepsy patients (age=30.79±10.30 years old; M:F=38:23) who underwent surgical treatments in Peking Union Medical College Hospital from April 2019 to April 2022 were enrolled in the study. Coagulation functions were evaluated using laboratory examination. Based on their perioperative medication, they were divided into two groups - sodium valproate and levetiracetam. We used t-test to measure the coagulation function parameters affected by the operation and then used independent t-test to determine the differences in coagulation function between the two groups.\u003c/p\u003e\n\u003cp\u003eResult\u003c/p\u003e\n\u003cp\u003eAbnormal PT, APTT, Fbg within 3 days after operation were found 84.8%, 28.3%, 93.5% respectively in patients using sodium valproate intravenous preparation, while these parameters are 26.7%, 26.7%, 26.7% respectively in patients using levetiracetam intravenous preparation. The patients who take sodium valproate intravenous preparation get higher value of PT increase in perioperative time compared to patient using levetiracetam intravenous preparation.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003ePatients with epilepsy are at risk of experiencing abnormal coagulation function following epilepsy surgery. It has been observed that patients may experience more severe and prolonged prothrombin time (PT) when using intravenous valproic acid preparation during the perioperative period, as compared to using levetiracetam intravenous preparation. These findings highlight the importance of monitoring coagulation function after epilepsy surgery. Surgeons should closely monitor patients who receive sodium valproate treatment during the perioperative period for any potential impact on their coagulation function post-surgery.\u003c/p\u003e","manuscriptTitle":"Analysis of perioperative period coagulation function affected by antiepileptic drugs in epilepsy surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-08 03:08:08","doi":"10.21203/rs.3.rs-4312766/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-03T10:26:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-30T15:05:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-30T15:05:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2024-04-23T14:09:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f3b94b6-260f-440e-ace0-819565ecef5b","owner":[],"postedDate":"May 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T16:02:26+00:00","versionOfRecord":{"articleIdentity":"rs-4312766","link":"https://doi.org/10.1186/s12871-025-03485-1","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-12-18 15:58:11","publishedOnDateReadable":"December 18th, 2025"},"versionCreatedAt":"2024-05-08 03:08:08","video":"","vorDoi":"10.1186/s12871-025-03485-1","vorDoiUrl":"https://doi.org/10.1186/s12871-025-03485-1","workflowStages":[]},"version":"v1","identity":"rs-4312766","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4312766","identity":"rs-4312766","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}