Impact of Thromboprophylaxis on Postoperative Complications in Glioblastoma Patients: Findings From a Prospective Study

Impact of Thromboprophylaxis on Postoperative Complications in Glioblastoma Patients: Findings From a Prospective Study | 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 Article Impact of Thromboprophylaxis on Postoperative Complications in Glioblastoma Patients: Findings From a Prospective Study Eva Wardenbach, Dino Podlesek, Boshr Alhasan, Ahmed Abouelhamd, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6448196/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted 8 You are reading this latest preprint version Abstract Thromboembolic events (TE) are serious complications following glioblastoma (GBM) resection. This retrospective study analyzed 695 GBM patients (2017–2022, University Hospital Dresden) to assess the impact of different anticoagulant regimens—certoparin, enoxaparin, and enoxaparin with intermittent pneumatic stockings (IPS)—along with patient comorbidities, on TE incidence. Overall, 28 patients (4%) developed TE. The highest combined incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in the enoxaparin group (8.6%), followed by certoparin (6.9%) and enoxaparin + IPS (2.6%) (p = .003). Increased PE risk was associated with longer surgery duration (median 249 vs. 190 min; p = .002), greater intraoperative blood loss (300 vs. 150 mL; p = .002), and older age (>65 years, p = .043). Comorbidities such as diabetes (p = .005) and coronary heart disease (p = .037) were also linked to elevated TE risk. Multivariate analysis identified enoxaparin alone as an independent risk factor (HR 0.312; CI 0.116–0.842; p = .022). Patients with PE or DVT had surgeries that were on average 45 minutes longer and involved higher blood loss. GBM patients treated with enoxaparin alone have a significant higher risk for TE compared to treatment with certoparin or the combination of enoxaparin with IPS. Additionally, the duration of surgery, patient age and comorbidities significantly influence the risk of postoperative TE. Health sciences/Medical research/Outcomes research Health sciences/Oncology/Cancer Health sciences/Oncology/Surgical oncology Health sciences/Medical research Health sciences/Oncology Health sciences/Risk factors Health sciences/Diseases/Cancer Thromboembolic events (TE) Glioblastoma Anticoagulant treatments Postoperative complications Risk factors Figures Figure 1 Introduction Glioblastoma WHO grade 4 (GBM) is the most prevalent and aggressive primary malignant brain tumor in adults, characterized by rapid progression and a poor prognosis [ 1 ]. Despite significant advances in surgical techniques, radiation and chemotherapy, the median survival remains limited to approximately 12 to 15 months after diagnosis [ 2 – 4 ]. In Germany, the incidence of GBM is approximately 6 per 100,000 individuals, accounting for around 5,000 new cases per annually [ 5 ]. The aggressive nature of the disease and the invasiveness of surgical interventions contribute to high morbidity and mortality rates [ 6 , 7 ]. Postoperative thromboembolic events (TE) such as deep vein thrombosis (DVT) and pulmonary embolism (PE) are serios complications frequently observed in neurosurgical patients, particularly those undergoing GBM resection [ 8 – 11 ]. The risk of TE in these patients is notably elevated due to a combination of factors, including prolonged immobility, surgical trauma and the prothrombotic state induced by cancer itself [ 12 , 13 ]. Existing literature reports incidence rates of DVT as high as 60% and PE rates up to 10% in GBM patients without thrombosis prophylaxis, with mortality from PE reaching 50% [ 3 , 12 , 14 – 16 ]. These events significantly impact patient outcome and quality of life, adding to the complexity of postoperative care [ 17 ]. The current recommendations of thromboprophylaxis in neurosurgical patients, particularly those undergoing GBM resection, are inconsistent and vary across institutions [ 5 , 18 – 21 ]. While mechanical prophylaxis, such as intermittent pneumatic stockings (IPS), is widely endorsed, pharmacological prophylaxis using low-molecular-weight heparins (LMWH) remains controversial and imprecise due to concerns about intracranial hemorrhage [ 11 , 18 ]. The S3 guideline for thromboprophylaxis offers only limited recommendations for neurosurgical patients, reflecting the lack of robust data specific to this group [ 21 ]. Moreover, no anticoagulants are officially approved for the use in neurosurgical patients by most manufacturers due to the perceived high risk of bleeding associated with central nervous surgery [ 22 , 23 ]. This open recommendation is based on a survey of 34 neurosurgical centers, which revealed that approximately 90% of clinics provide their patients with LMWH postoperatively [ 24 ]. There is a strong recommendation for mechanical prophylaxis, for example, the use of IPS. The benefit of this approach was clearly demonstrated in several prospective, randomized studies and justified in a metanalysis of 30 publications of 7779 patients who underwent neurosurgical surgery [ 18 ]. Given these challenges, there is an urgent need to evaluate the efficacy and safety of various thromboprophylaxis strategies in patients undergoing GBM surgery [ 11 , 14 ]. This study seeks to address these gaps by analyzing the impact of different anticoagulation regimes, including certoparin, enoxaparin and the combination of enoxaparin with IPS, on the incidence of postoperative symptomatic TE. Additionally, patient-specific and procedure-specific risk factors for symptomatic TE are examined to improve risk stratification in this high-risk population. The goal is to provide evidence-based recommendations that can guide clinical practice and enhance patient outcomes by reducing the incidence of symptomatic TE while minimizing the risk of hemorrhagic complications. In this context, this study aims to contribute to the growing body of literature by providing insights into the comparative effectiveness of different prophylaxis strategies in GBM patients, a population that remains understudied despite their high vulnerability to both symptomatic TE and bleeding complications [ 25 ]. By evaluating the outcome associated with these strategies, we hope to inform future guidelines and help optimize postoperative care for patients undergoing neurosurgical procedures. Methods Study Design and Population This prospective observational study consists of 695 patients with newly diagnosed glioblastoma, who underwent surgical treatment between February 2017 and June 2022. Eligibility required patients to be at least 18 years old with histologically confirmed GBM according to the previous WHO classification. Surgical resection was performed in all cases unless contraindications such as tumor size, location or intraoperative complications like excessive bleeding were present. The cohort size was determined by the complete data available for all GBM surgeries conducted during the study period. This cohort size was sufficient for identifying statistically significant associations between thromboprophylaxis strategies and TE, as well as for conducting subgroup analyses. The cohort size allowed for robust statistical analysis, while the inclusion criteria ensured a representative sample of the target population. Detailed demographic characteristics are summarized in table 1. The study aimed to investigate the effectiveness of different thromboprophylaxis strategies, specifically comparing pharmacological and mechanical interventions. Patients with comorbidities or a history of TE were not excluded from the study, allowing for a comprehensive analysis of risk factors. Thromboprophylaxis Interventions This study assessed three distinct thromboprophylaxis regimens: Certoparin group (n=304): Patients received certoparin, a LMWH as pharmacological prophylaxis. Enoxaparin group (n=163): Patients received enoxaparin for anticoagulation Enoxaparin combined with IPS (n=228): Patients received enoxaparin in combination with mechanical prophylaxis using IPS. All patients were followed for three months postoperatively, and data on the incidence of symptomatic DVT and PE were collected. No routine screening for asymptomatic TE was performed; only symptomatic cases were detected according to existing standard operation procedures using duplex ultrasound or computer tomography. Data Collection and Risk Factors The investigators had full access to the electronic medical records (EMRs) of all GBM patients treated at the University Hospital Dresden during the study period. These records provided comprehensive data on demographics, clinical characteristics, surgical parameters, and postoperative outcomes, authorized through institutional approval and ethics committee supervision (approval number EK63022018). The centralized EMR system ensured reliable and complete datasets for analysis, without missing data on key variables. Efforts to minimize bias included systematic data collection by trained staff, excluding patients with incomplete follow-up, and confirming symptomatic TE using established diagnostic methods like duplex ultrasound and CT, to ensure consistency and accuracy. The study included all eligible patients, accounting for confounders such as comorbidities and procedure-specific parameters using multivariate logistic regression. Patient-specific risk factors analyzed included age, gender, comorbidities (e.g., epilepsy, diabetes, CHD, atrial fibrillation, hypertension), medication, and prior TE history. Procedure-specific factors included surgery duration, intraoperative blood loss, postoperative thromboprophylaxis, and the use of IPS versus non-pneumatic stockings. Outcome Measures The primary outcome measure was the occurrence of symptomatic DVT, PE or both within three months post-surgery. The identification of DVT was based on duplex ultrasound, while PE was diagnosed using computer tomography. Statistical Analysis The statistical analyses were conducted using the IBM SPSS Statistics software, version 29.0. Descriptive statistics were used to summarize patient characteristics and clinical outcomes, ensuring meaningful and comprehensive data analysis. Quantitative variables, such as age, surgery duration, and intraoperative blood loss, were initially analyzed as continuous variables and expressed as medians with ranges. Subsequently, these variables were categorized using clinically relevant thresholds from the literature (e.g., surgery duration >200 minutes, blood loss >200 mL) to facilitate subgroup analyses and improve clinical interpretability. Categorical variables were summarized as absolute frequencies and percentages. The relationships between these variables and the risk of thromboembolic events (TE) were explored using descriptive statistics (e.g., medians and interquartile ranges) and hypothesis tests. Pearson’s chi-square test was applied to categorical variables, while the Mann-Whitney U-test was used to compare continuous variables. A p-value < 0.05 was considered statistically significant in all analyses. To identify independent predictors of TE, a multivariate binary logistic regression model was developed. Variables with significant associations in the univariate analysis were included in the regression and refined through backward elimination, progressively removing non-significant factors. The final model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to quantify the strength of associations between risk factors and TE. The model’s explanatory power was evaluated using the Nagelkerke R² statistic and the omnibus test of model coefficients, with a p-value < 0.05 indicating satisfactory model performance. This analytical approach ensured robust control for potential confounders and allowed for clinically relevant insights into the relationships between patient characteristics, surgical factors, and the risk of symptomatic TE. Results Study Population A total of 695 patients were included in the analysis, comprising 264 women (38%) and 431 men (62%). The median age of the cohort was 64 years (range: 20–95 years). Detailed demographic and clinical characteristics are shown in Table 1 and 2 . Frequency of symptomatic TE (DVT/PE) In the cohort, 28 patients (4%) experienced symptomatic TE, which included DVT and PE. Specifically, 3% of patients developed symptomatic DVT, 2,9% developed symptomatic PE and 4% experienced both symptomatic DVT and PE within the three-month postoperative period. Thromboprophylaxis group as risk of TE The frequency of thromboembolic complications varied significantly across the three thromboprophylaxis groups (Fig. 1). Patients in the enoxaparin group (group 2) exhibited a higher incidence of both symptomatic DVT and PE compared to the certoparin group (group 1), and the enoxaparin combined with IPS Group (group 3). The incidence for symptomatic DVT were 5.5% for group 2, compared to 2.6% in group 1 and 1.8% in group 3 without significance (p = .088). Patients in group 2 (8.6%) suffered significant more often from symptomatic DVT than in the other prophylaxis groups (group 1 and 2: both 2.6%) (p = .003). The combined incidence of symptomatic DVT and PE was 8.6% in group 2, 6.9% in group 1, and 2.6% in group 3 (p = .003). The incidence of DVT/PE is significantly higher in group 2 than in group 1 and 3 (p = .003). This result is confirmed by multivariate analysis for DVT/PE: p = .022 (HR:0,312; CI:0,116-0,842). Patient-specific risk factors Several patient-specific risk factors were identified as significantly associated with the incidence of symptomatic TE. Older patients (aged over 65 years) were found to have higher prevalence of symptomatic PE (4.3%) compared to younger patients (1.6%; p=.043). Additionally, patients with a median age of 68 years were more likely to experience symptomatic TE compared to younger patients (p=.041). While GBM was more common in men (p=<.001), male sex was not found to be a significant risk factor for symptomatic TE. No statistically significant differences were observed in the incidence of symptomatic DVT (p=.25), PE (p=.106) or combined symptomatic DVT/PE (p=.075) between male and female patients. CHD was associated with higher incidence of symptomatic PE (8.7% in CHD patients vs. 2.5% in non-CHD patients; p=.037). Additionally, patients with diabetes mellitus had a significantly increased risk of symptomatic PE (p=.006) and combined symptomatic DVT/PE (p=.005). The incidence of symptomatic PE in diabetes patients was 7.5%, and 9.4% developed both symptomatic DVT and PE, compared to 2.0% and 3.1% respectively, in non-diabetic patients. Conversely, hypertension has no significant effect on the occurrence of symptomatic DVT (1.8% with no TE vs 3.9% with DVT, p=.17) or symptomatic PE (1.8% with no TE vs 3.6%, p =.17 with PE). However, there is a significant effect on the occurrence of both symptomatic DVT and PE combined (2.1% with no TE vs 5.3%, p =.048 with DVT/PE). Epilepsy was also not associated with a higher risk of any symptomatic TE: DVT: p=.662, PE: p=.822, DVT/PE: p=.442. A diagnosis of atrial fibrillation was recorded in 7.6% of the cohort. There was no evidence that the presence of atrial fibrillation increased the risk of symptomatic TE, as demonstrated by the following p-values: DVT (p=.66), PE (p=.65), and DVT/PE (p=.459). Similarly, a history of TE did not affect the subsequent incidence of symptomatic TE following surgical resection of GBM: DVT (p=.17), PE (p=.154), and DVT/PE (p=.121). Procedure specific risk factors Procedure-specific factors also played a significant role in the development of symptomatic TE. Longer surgeries were associated with a higher risk of symptomatic PE. Patients who developed symptomatic PE had a median surgical time of 249 minutes compared to 190 minutes for the overall cohort (p=.002). Additionally, surgeries in patients with combined symptomatic DVT/PE were on average 43 minutes longer than those without symptomatic thromboembolic complications (p=.011). Intraoperative blood loss was another significant risk factor. Patients who developed symptomatic PE lost a median of 300mL of blood compared to 150mL in patients without symptomatic PE (p=.002). Similarly, patients with combined symptomatic DVT/PE experienced greater blood loss (median 200mL; p=.012). The majority of patients (76.8%) were positioned supine during surgery, followed by, prone (14.9%), lateral (8.1%) and Trendelenburg position (0.1%). However, the small sample sizes of the individual subgroups limited meaningful statistical evaluation of these data. Independent predictors for symptomatic TE Multivariate binary logistic regression analysis was performed to identify independent predictors of symptomatic TE (table 3). The prophylaxis group was determined to be an independent predictor for the occurrence of symptomatic TE. Specifically, patients in the enoxaparin-only group exhibited a significantly higher risk of symptomatic TE compared to the other groups (hazard ratio (HR) 0.312, 95% CI 0.116-0.842; p=.022). Additionally, diabetes mellitus emerged as a patient-specific independent risk factor for the occurrence of symptomatic PE (p=.007, HR 3.6, 95% CI 1.4–9.2) and combined symptomatic DVT/PE (p=.009, HR 3.0, 95% CI 1.3–6.8). Among the procedure-specific factors, longer surgery duration was identified as an independent predictor for symptomatic DVT (p=.047, HR 2.5, 95% CI 1.0–6.4), symptomatic PE (p=.045, HR 2.9, 95% CI 1.0–8.4), combined symptomatic DVT/PE (p=.039, HR 2.6, 95% CI 1.6–6.5). Similarly, increased blood loss was a significant predictor for the occurrence of symptomatic PE (p=.03, HR 0.35, 95% CI 0.14–0.9). Conclusion The relationship between GBM and thrombosis has become increasingly well-understood through ongoing research. This study emphasizes the need to differentiate between perioperative prophylaxis strategies for GBM patients. Our findings indicate that GBM patients treated solely with enoxaparin had a significant higher risk for symptomatic TE compared to those treated with certoparin or a combination of enoxaparin and IPS. Similar to other studies, we found that combining LMWH with IPS yielded the best patient outcome [26]. As there are currently no specific guidelines on the preferred LMWH, and given the efficacy highlighted in our study, further research is needed to fully understand the varying impact of different agents. Additionally, factors such as age above 65, pre-existing comorbidities like diabetes and hypertension, longer surgery duration (>200min) and higher intraoperative blood loss (>200mL) were identified as significant risk factors for symptomatic TE (table 4). Conversely, factors such as sex, epilepsy, atrial fibrillation, and a history of TE were not found to increase the risk. From our study, three key points emerge: Low molecular weight heparins = “same, same but different”? While general guidelines exist for postoperative thromboprophylaxis in cancer patients, the selection of a specific LMWH remains a subject of ongoing debate [5,19,20]. Increasing evidence in neurosurgery supports the use of LMWHs, which do not significantly increase the risk of postoperative intracranial hemorrhage when doses are controlled (<4000I U/day) and administrated the day after surgery [18,27]. To date, no clear recommendations exist regarding the most appropriate LMWH, such as certoparin, enoxaparin, dalteparin or nadroparin, and whether their effectiveness in reducing symptomatic TE varies. Given that LMWHs are derived from different manufacturing processes, resulting in varied molecular compositions, it is unsurprising that they may differ in function. LMWHs share a mechanism of action that involves antithrombin-mediated inhibition of factor Xa, along with several pleiotropic effects, but no two LMWHS are exactly alike [28–30]. For example, enoxaparin products like Clexane (est. 1994) and Inhixa (est. 2017), though both classified as LMWHs, differ in their properties due to their unique production processes. While marketed as biosimilars, these products are not identical. Inhixa, introduced in 2017 under revised European Medicines Agency (EMA) approval processes [31], was approved through a simplified regulatory process as part of EU harmonization efforts, despite being a complex mixture of biogenic origin. The potential clinical value of a biosimilar can be assessed using the System of Objectified Judgement Analysis (SOJA). In this case, the total score would currently fall significantly below 1000 points, the target value, due to the lack of clinical data [32]. This raises concerns about clinical efficacy and bioequivalence, even between Inhixa and Clexane, both of which are enoxaparin. Due to the varying chemical modifications introduced by each manufacturing process, LMWHs from different manufacturers are not identical chemical entities [28,33,34]. Imberti et al. recommended in their review from 2017 to not follow the changed EMA approval of enoxaparin biosimilars, due to serious concerns regarding efficacy and safety [33]. Studies have shown that Inhixa has only 85% of the tissue factor pathway inhibitor (TFPI) activity of Clexane, suggesting potential differences in therapeutic efficacy [22,29]. On the other hand, in 2020, Fantoni et al. conducted a retrospective observational report on the safety and efficacy of biosimilar enoxaparin in 189 medical and 192 general surgical patients. All surgical patients underwent major abdominal surgery, again highlighting the lack of representation of neurosurgical patients, who were excluded from the studies. Fantoni et al. found that the incidence of bleeding and VTE was 0.5%, which is comparable to the estimated rates in their literature analysis [35]. Further research is needed to fully understand these differences and their clinical implications, and to re-evaluate and discuss the changes in the EMA approval process. We have not yet compared our subgroups based on Inhixa or Clexane, but this will be an interesting target for the future. Our study found that certoparin was more effective than enoxaparin, raising questions about possible pharmacokinetic differences despite their apparently similar properties such as half-life and bioavailability. Further research is needed to determine whether these differences impact patient outcomes, and ongoing studies should explore the bioequivalence and pharmacokinetics of biosimilars like Inhixa and Clexane. Intermittent Pneumatic Stockings Our finding suggests that patients receiving certoparin had a comparable low incidence of symptomatic TE, similar to those receiving enoxaparin in combination with IPS, but those treated with enoxaparin without IPS exhibited significantly higher symptomatic TE incidence. This highlights the potential importance of IPS in thromboprophylaxis. While current S3 guideline recommend the use of IPS, no studies have specifically evaluated the combination of IPS with different LMWHs to determine which combination offers the best protection against thromboembolic complications [18,19,21,36]. Further studies are required to investigate whether adding IPS to certoparin or even using IPS alone could lead to similarly effective outcomes. Understanding the interplay between these interventions could refine prophylactic strategies, particularly for high-risk patients. Predictive score The widely used Khorana score for predicting symptomatic TE in cancer patients has been shown to be inapplicable to patients with GBM [37]. While highly sensitive (98%) for predicting symptomatic TE, its specificity in GBM populations is low (5,6%), as Yust-Katz et al. showed 2014 in their clinical study (n=418) [38]. Khorana himself acknowledged that the data set used to develop the Khorana Score included only a small number of brain tumor patients (n=4). In addition, patients with poor performance status were underrepresented in the cohort, which may limit the applicability of the score to these populations [39]. The Khorana score is made up of the following parameters: 1) cancer type; 2) pre-chemo platelet count; 3) hemoglobin level; 4) pre-chemo leukocyte count; 4) body-mass-index. In 2022, Bell Burdett et al. presented a new predictive time-to-event-model that incorporates additional parameters, to more accurately reflect the complex nature of GBM: 1) history of TE; 2) hypertension; 3) asthma; 4) white blood cell count; 5) WHO tumor grade; 6) patient age; 7) body-mass-index. They created a web based TE prediction tool that was validated in two separate cohorts [40]. Our study confirmed the risk factors hypertension and patients age, but also integrated further risk factors, such as surgery duration and intraoperative blood loss, that could augment Bell's score by incorporating procedure-specific elements. Future efforts should aim to integrate these factors into a more comprehensive and clinically practical scoring system Limitations This study has several limitations, including a relatively small sample size, especially for patients with symptomatic TE, which may contribute to variability in the statistical analysis. The single-center design and potential reporting bias (underreporting) limit the generalizability of the findings. Additionally, TE were identified solely based on patient complaints, and using a standardized screening instrument to assess typical TE symptoms in each patient would have been beneficial. A comparison group for the combination of certoparin and IPS was not feasible due to supply issues with certoparin starting in 2019. Our objective was to compare our in-house prophylaxis measures with each other and to identify risk factors. We were able to achieve meaningful results in this regard. Given the medical context, we focused on clinical parameters. Another improvement would be the collection of laboratory markers for coagulation factors to compare the performance of Khorana’s and Bell’s predictive models. This would provide insights into their accuracy and applicability to this specific patient population. However, this study offers clinically relevant findings that can help develop more precise risk profiles for GBM patients in future research. An easy-to-use predictive model would be beneficial for better assessing individual patient risk and tailoring treatment strategies. Further investigation into the pharmacokinetic differences between various LMWHs and the bioequivalence of biosimilars like Inhixa and Clexane remains crucial. In conclusion, this study highlights the importance of selecting the right thromboprophylaxis strategy for GBM patients to minimize postoperative complications. Our findings contribute to optimizing postoperative care and provide valuable directions for future research on personalized thromboprophylaxis. Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by WHP and EW. The first draft of the manuscript was written by EW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Hospital of Dresden ( EK63022018). Informed Consent Statement All patients provided written informed consent for the use of their clinical data for research purposes as part of the treatment contract with the University Hospital Dresden. References Ferlay, J., Parkin, D. M. & Steliarova-Foucher, E. 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Fantoni, C. et al. Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients. Intern. Emerg. Med. Juni . 16 (4), 933–939 (2021). Turpie, A. G., Hirsh, J., Gent, M., Julian, D. & Johnson, J. Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control. Arch. Intern. Med. 149 (3), 679–681 (März 1989). Huang, X. et al. u. a. External validation of the Khorana score for the prediction of venous thromboembolism in cancer patients: A systematic review and meta-analysis. Int. J. Nurs. Stud. November . 159 , 104867 (2024). Yust-Katz, S. et al. u. a. Venous thromboembolism (VTE) and glioblastoma. J. Neurooncol August . 124 (1), 87–94 (2015). Khorana, A. A., Kuderer, N. M., Culakova, E., Lyman, G. H. & Francis, C. W. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 15 Mai . 111 (10), 4902–4907 (2008). Bell Burdett, K. VTE Prediction for Pateients with Glioma [Internet]. [zitiert 18. September 2024]. Verfügbar unter: https://kbellburdett.shinyapps.io/GliomaPredictVTE/ Tables Table 1: Demographic and clinical characteristics of the study cohort Characteristic Value Age in years, median 64 (20-94) Female sex, n (%) 264 (38) Comorbidities, n (%) Epilepsy Arterial hypertension Diabetes mellitus 1 / 2 Chronic heart disease Atrial fibrillation Prior thromboembolic event 301 (43.3) 415 (59.7) 106 (15.3) 46 (6.6) 53 (7.6) 48 (6.9) Clinical parameters, median Duration of surgery, minutes Blood loss, milliliter 191 150 Thromboembolic complications, n (%) Deep vein thrombosis Pulmonary embolism Deep vein thrombosis/Pulmonary embolism 21 (3) 20 (2.9) 28 (4) Table 2: Demographic and clinical parameters stratified by thromboembolic events Characteristic TE positive TE negative p-value Median age, year (IQR) 68 63 .041 Sex, n (%) Female Male 6 (2.3) 22 (5.1) 257 (97.7) 409 (94.4) .075 Comorbidities, n (%) Hypertonus (414) 22 (5.3) 392 (94.7) .048 Chronic heart disease (46) 4 (8.7) 42 (91.3) .107 Epilepsy (301) 10 (3.3) 291 (96.7) .442 Diabetes (106) 10 (9.4) 96 (90.6) .005 Atrial fibrillation (52) 3 (5.8) 49 (94.2) .459 Prior TE (48) 4 (8.3) 44 (91.7) .121 Prophylaxis group, n (%) Certoparin Enoxaparin Enoxaparin + IPS 8 (2.6) 14 (8.6) 6 (2.6) 296 (97.4) 149 (91.4) 221 (97.4) .003 Blood loss Median blood loss, mL Blood loss > 200mL, n (%) 200 13 (6.4) 150 190 (93.6) .012 .059 Duration of surgery Median duration, min Duration > 200min, n (%) 234 20 (6.4) 189 291 (93.6) .011 .006 Abbreviations: TE, thromboembolic event; IPS, intermittent pneumatic stockings; mL, milliliters; min, minutes . Table 3: Results of the multivariate analysis: Independent, prognostic risk factors DVT Sig (p) HR PE Sig (p) HR DVT/PE Sig (p) HR Patient specific DM 1/2 x .007 3.6 x .009 3.0 Procedure specific Surgery duration x .047 2.5 x .045 2.9 x .04 2.6 Blood loss x .03 0.35 Prophylaxis specific Enoxaparin x .022 0.3 Abbreviations: TE, thromboembolic event; DVT, deep vein thrombosis; PE, pulmonary embolism; DM 1/2, diabetes mellitus 1/2; Sig (p), significance (p-value); HR, hazard ratio. Table 4: Risk factors for thromboembolic events in patients with glioblastoma Patient specific Procedure specific Prophylaxis specific Age > 65years CHD DM ½ Hypertension Blood loss > 200mL Surgery duration >200min Monotherapy with enoxaparin Abbreviations: CHD, chronic heart disease; DM 1/2, diabetes mellitus type ½; mL, milliliter; min, minutes, IPS, intermittent pneumatic stockings. Additional Declarations No competing interests reported. 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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-6448196","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":454260316,"identity":"4318b60c-5a0f-47b8-ae53-60cac4798e38","order_by":0,"name":"Eva Wardenbach","email":"","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Wardenbach","suffix":""},{"id":454260317,"identity":"3aef68c1-4f8d-41e8-b0aa-71d628660ce0","order_by":1,"name":"Dino Podlesek","email":"","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":false,"prefix":"","firstName":"Dino","middleName":"","lastName":"Podlesek","suffix":""},{"id":454260318,"identity":"2252256a-926d-4bd2-a99f-f311a9de2375","order_by":2,"name":"Boshr Alhasan","email":"","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":false,"prefix":"","firstName":"Boshr","middleName":"","lastName":"Alhasan","suffix":""},{"id":454260319,"identity":"eeeaa018-0c9c-4129-8a78-925ecf2b69d1","order_by":3,"name":"Ahmed Abouelhamd","email":"","orcid":"","institution":"Fichtelgebirge Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Abouelhamd","suffix":""},{"id":454260320,"identity":"12eb45d5-21c5-4a80-b94a-c87bb6f494d5","order_by":4,"name":"Ilker Y. Eyüpoglu","email":"","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":false,"prefix":"","firstName":"Ilker","middleName":"Y.","lastName":"Eyüpoglu","suffix":""},{"id":454260321,"identity":"c410a9c8-9d48-41dc-a6d7-fa4015674567","order_by":5,"name":"Tareq A. Juratli","email":"","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":false,"prefix":"","firstName":"Tareq","middleName":"A.","lastName":"Juratli","suffix":""},{"id":454260322,"identity":"8bea6e01-47a5-4d87-ba1b-3abcf0166cd3","order_by":6,"name":"Witold H. Polanski","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIie3QsWrDMBCA4QsCeRHNeibQvoKKwXUhNK9yJtBMnQIak0LAXQqZ+xbJ0tlBkC6Ks3p0ls6eirdWIYHSguyOHfQPQgf6QBKAz/cPk9ouFYc5BMcxx0sQIBF4G2EAxCF9ZCcSdZP8J7GbTvLW31SkIF0y9n5oTDJZGb0uQQ2dJNaMSSpgHi74TSRKfFjtsmkCxX0b4ZhmQPYf4gHUluxFjL1M/4UEH2FT40SeyKeTjL6JPWkvRnL3fCS5k9xqFtm3IIULoQbC4PWL2U4TKsZOIvebQ1WrIfWDp9ew2c6uLsx4XdbqzknO4a+ZuoDP5/P5WvsC8KVT6iaqfFMAAAAASUVORK5CYII=","orcid":"","institution":"University Hospital Dresden","correspondingAuthor":true,"prefix":"","firstName":"Witold","middleName":"H.","lastName":"Polanski","suffix":""}],"badges":[],"createdAt":"2025-04-14 17:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6448196/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6448196/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-07899-2","type":"published","date":"2025-07-01T15:58:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82758850,"identity":"2193fd49-0f5d-4e05-9fef-04369d7bf24b","added_by":"auto","created_at":"2025-05-15 02:23:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13070,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eThe prophylaxis group is an independent prognostic risk factor for TE.\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe incidence of DVT/PE is significantly higher in group 2 than in group 1 and 3 (p=.003). This result is confirmed by multivariate analysis for DVT/PE: p=.022 (HR:0,312; CI:0,116-0,842).\u003c/p\u003e\n\u003cp\u003eAbbreviations: TE, thromboembolic event; DVT, deep vein thrombosis; PE, pulmonary embolism; IPS, intermittent pneumatic stockings\u003c/p\u003e","description":"","filename":"Onlinedrawingimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6448196/v1/54d048fa7f5ceb6451509a14.png"},{"id":86179609,"identity":"e98eb00f-8e53-486b-abbd-dabee95c1b44","added_by":"auto","created_at":"2025-07-07 16:17:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":716565,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6448196/v1/be653a1d-b53c-45cb-82b5-31bf44464a98.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eImpact of Thromboprophylaxis on Postoperative Complications in Glioblastoma Patients: Findings From a Prospective Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlioblastoma WHO grade 4 (GBM) is the most prevalent and aggressive primary malignant brain tumor in adults, characterized by rapid progression and a poor prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite significant advances in surgical techniques, radiation and chemotherapy, the median survival remains limited to approximately 12 to 15 months after diagnosis [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In Germany, the incidence of GBM is approximately 6 per 100,000 individuals, accounting for around 5,000 new cases per annually [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The aggressive nature of the disease and the invasiveness of surgical interventions contribute to high morbidity and mortality rates [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePostoperative thromboembolic events (TE) such as deep vein thrombosis (DVT) and pulmonary embolism (PE) are serios complications frequently observed in neurosurgical patients, particularly those undergoing GBM resection [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The risk of TE in these patients is notably elevated due to a combination of factors, including prolonged immobility, surgical trauma and the prothrombotic state induced by cancer itself [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Existing literature reports incidence rates of DVT as high as 60% and PE rates up to 10% in GBM patients without thrombosis prophylaxis, with mortality from PE reaching 50% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These events significantly impact patient outcome and quality of life, adding to the complexity of postoperative care [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The current recommendations of thromboprophylaxis in neurosurgical patients, particularly those undergoing GBM resection, are inconsistent and vary across institutions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. While mechanical prophylaxis, such as intermittent pneumatic stockings (IPS), is widely endorsed, pharmacological prophylaxis using low-molecular-weight heparins (LMWH) remains controversial and imprecise due to concerns about intracranial hemorrhage [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The S3 guideline for thromboprophylaxis offers only limited recommendations for\u003c/p\u003e \u003cp\u003eneurosurgical patients, reflecting the lack of robust data specific to this group [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, no anticoagulants are officially approved for the use in neurosurgical patients by most\u003c/p\u003e \u003cp\u003emanufacturers due to the perceived high risk of bleeding associated with central nervous surgery [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This open recommendation is based on a survey of 34 neurosurgical centers, which revealed that approximately 90% of clinics provide their patients with LMWH postoperatively [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. There is a strong recommendation for mechanical prophylaxis, for example, the use of IPS. The benefit of this approach was clearly demonstrated in several prospective, randomized studies and justified in a metanalysis of 30 publications of 7779 patients who underwent neurosurgical surgery [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Given these challenges, there is an urgent need to evaluate the efficacy and safety of various thromboprophylaxis strategies in patients undergoing GBM surgery [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This study seeks to address these gaps by analyzing the impact of different anticoagulation regimes, including certoparin, enoxaparin and the combination of enoxaparin with IPS, on the incidence of postoperative symptomatic TE. Additionally, patient-specific and procedure-specific risk factors for symptomatic TE are examined to improve risk stratification in this high-risk population. The goal is to provide evidence-based recommendations that can guide clinical practice and enhance patient outcomes by reducing the incidence of symptomatic TE while minimizing the risk of hemorrhagic complications. In this context, this study aims to contribute to the growing body of literature by providing insights into the comparative effectiveness of different prophylaxis strategies in GBM patients, a population that remains understudied despite their high vulnerability to both symptomatic TE and bleeding complications [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. By evaluating the outcome associated with these strategies, we hope to inform future guidelines and help optimize postoperative care for patients undergoing neurosurgical procedures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cu\u003eStudy Design and Population\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective observational study consists of 695 patients with newly diagnosed glioblastoma, who underwent surgical treatment between February 2017 and June 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEligibility required patients to be at least 18 years old with histologically confirmed GBM according to the previous WHO classification. \u0026nbsp;Surgical resection was performed in all cases unless contraindications such as tumor size, location or intraoperative complications like excessive bleeding were present.\u0026nbsp;The cohort size was determined by the complete data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eavailable for all GBM surgeries conducted during the study period. This cohort size was\u003c/p\u003e\n\u003cp\u003esufficient for identifying statistically significant associations between thromboprophylaxis strategies and TE, as well as for conducting subgroup analyses. The cohort size allowed for robust statistical analysis, while the inclusion criteria ensured a representative sample of the target population.\u0026nbsp;Detailed demographic characteristics are summarized in table 1.\u003c/p\u003e\n\u003cp\u003eThe study aimed to investigate the effectiveness of different thromboprophylaxis strategies, specifically comparing pharmacological and mechanical interventions. Patients with comorbidities or a history of TE were not excluded from the study, allowing for a comprehensive analysis of risk factors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eThromboprophylaxis Interventions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study assessed three distinct thromboprophylaxis regimens:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eCertoparin group (n=304): Patients received certoparin, a LMWH as pharmacological prophylaxis.\u003c/li\u003e\n \u003cli\u003eEnoxaparin group (n=163): Patients received enoxaparin for anticoagulation\u003c/li\u003e\n \u003cli\u003eEnoxaparin combined with IPS (n=228): Patients received enoxaparin in combination with mechanical prophylaxis using IPS.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAll patients were followed for three months postoperatively, and data on the incidence of symptomatic DVT and PE were collected. No routine screening for asymptomatic TE was performed; only symptomatic cases were detected according to existing standard operation procedures using duplex ultrasound or computer tomography.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eData Collection and Risk Factors\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe investigators had full access to the electronic medical records (EMRs) of all GBM patients treated at the University Hospital Dresden during the study period. These records provided comprehensive data on demographics, clinical characteristics, surgical parameters, and postoperative outcomes, authorized through institutional approval and ethics committee supervision (approval number EK63022018).\u0026nbsp;The centralized EMR system ensured reliable and complete datasets for analysis, without missing data on key variables. Efforts to minimize\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ebias included systematic data collection by trained staff, excluding patients with incomplete follow-up, and confirming symptomatic TE using established diagnostic methods like duplex ultrasound and CT, to ensure consistency and accuracy. The study included all eligible patients, accounting for confounders such as comorbidities and procedure-specific parameters using multivariate logistic regression. Patient-specific risk factors analyzed included age,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003egender, comorbidities (e.g., epilepsy, diabetes, CHD, atrial fibrillation, hypertension), medication, and prior TE history. Procedure-specific factors included surgery duration,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eintraoperative blood loss, postoperative thromboprophylaxis, and the use of IPS versus non-pneumatic stockings.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eOutcome Measures\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was the occurrence of symptomatic DVT, PE or both within three months post-surgery. The identification of DVT was based on duplex ultrasound, while PE was diagnosed using computer tomography.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eStatistical Analysis\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe statistical analyses were conducted using the IBM SPSS Statistics software, version 29.0. Descriptive statistics were used to summarize patient characteristics and clinical outcomes, ensuring meaningful and comprehensive data analysis. Quantitative variables, such as age, surgery duration, and intraoperative blood loss, were initially analyzed as continuous variables and expressed as medians with ranges. Subsequently, these variables were categorized using clinically relevant thresholds from the literature (e.g., surgery duration \u0026gt;200 minutes, blood loss \u0026gt;200 mL) to facilitate subgroup analyses and improve clinical interpretability. Categorical variables were summarized as absolute frequencies and percentages. The relationships between these variables and the risk of thromboembolic events (TE) were explored using descriptive statistics (e.g., medians and interquartile ranges) and hypothesis tests. Pearson’s chi-square test was applied to categorical variables, while the Mann-Whitney U-test was used to compare continuous variables. A p-value \u0026lt; 0.05 was considered statistically significant in all analyses. To identify independent predictors of TE, a multivariate binary logistic regression model was developed. Variables with significant associations in the univariate analysis were included in the regression and refined through backward elimination, progressively removing non-significant factors. The final model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to quantify the strength of associations between risk factors and TE.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe model’s explanatory power was evaluated using the Nagelkerke R² statistic and the omnibus test of model coefficients, with a p-value \u0026lt; 0.05 indicating satisfactory model performance.\u003c/p\u003e\n\u003cp\u003eThis analytical approach ensured robust control for potential confounders and allowed for clinically relevant insights into the relationships between patient characteristics, surgical factors, and the risk of symptomatic TE.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Population\u003c/h2\u003e\n \u003cp\u003eA total of 695 patients were included in the analysis, comprising 264 women (38%) and 431 men (62%). The median age of the cohort was 64 years (range: 20\u0026ndash;95 years). Detailed demographic and clinical characteristics are shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eFrequency of symptomatic TE (DVT/PE)\u003c/h3\u003e\n\u003cp\u003eIn the cohort, 28 patients (4%) experienced symptomatic TE, which included DVT and PE. Specifically, 3% of patients developed symptomatic DVT, 2,9% developed symptomatic PE and 4% experienced both symptomatic DVT and PE within the three-month postoperative period.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eThromboprophylaxis group as risk of TE\u003c/h2\u003e\n \u003cp\u003eThe frequency of thromboembolic complications varied significantly across the three thromboprophylaxis groups (Fig. 1). Patients in the enoxaparin group (group 2) exhibited a higher incidence of both symptomatic DVT and PE compared to the certoparin group (group 1), and the enoxaparin combined with IPS Group (group 3). The incidence for symptomatic DVT were 5.5% for group 2, compared to 2.6% in group 1 and 1.8% in group 3 without significance (p\u0026thinsp;=\u0026thinsp;.088). Patients in group 2 (8.6%) suffered significant more often from symptomatic DVT than in the other prophylaxis groups (group 1 and 2: both 2.6%) (p\u0026thinsp;=\u0026thinsp;.003). The combined incidence of symptomatic DVT and PE was 8.6% in group 2, 6.9% in group 1, and 2.6% in group 3 (p\u0026thinsp;=\u0026thinsp;.003).\u003c/p\u003e\n \u003cp\u003eThe incidence of DVT/PE is significantly higher in group 2 than in group 1 and 3 (p\u0026thinsp;=\u0026thinsp;.003). This result is confirmed by multivariate analysis for DVT/PE: p\u0026thinsp;=\u0026thinsp;.022 (HR:0,312; CI:0,116-0,842).\u003c/p\u003e\n \u003cp\u003e\u003cu\u003ePatient-specific risk factors\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eSeveral patient-specific risk factors were identified as significantly associated with the incidence of symptomatic TE. Older patients (aged over 65 years) were found to have higher prevalence of symptomatic PE (4.3%) compared to younger patients (1.6%; p=.043). Additionally, patients with a median age of 68 years were more likely to experience symptomatic TE compared to younger patients (p=.041).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWhile GBM was more common in men (p=\u0026lt;.001), male sex was not found to be a significant risk factor for symptomatic TE. No statistically significant differences were observed in the incidence of symptomatic DVT (p=.25), PE (p=.106) or combined symptomatic DVT/PE\u003c/p\u003e\n \u003cp\u003e(p=.075) between male and female patients. CHD was associated with higher incidence of\u0026nbsp;symptomatic\u0026nbsp;PE (8.7% in CHD patients vs. 2.5% in non-CHD patients; p=.037). Additionally, patients with diabetes mellitus had a significantly increased risk of symptomatic PE (p=.006) and combined symptomatic DVT/PE (p=.005). The incidence of symptomatic PE in diabetes patients was 7.5%, and 9.4% developed both symptomatic DVT and PE, compared to 2.0% and 3.1% respectively, in non-diabetic patients. Conversely, hypertension has no significant effect on the occurrence of symptomatic DVT (1.8% with no TE vs 3.9% with DVT, p=.17) or symptomatic PE (1.8% with no TE vs 3.6%, p =.17 with PE). However, there is a significant effect on the occurrence of both symptomatic DVT and PE combined (2.1% with no TE vs 5.3%, p =.048 with DVT/PE). Epilepsy was also not associated with a higher risk of any symptomatic TE: DVT: p=.662, PE: p=.822, DVT/PE: p=.442.\u003c/p\u003e\n \u003cp\u003eA diagnosis of atrial fibrillation\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewas recorded in 7.6% of the cohort. There was no evidence that the presence of atrial fibrillation increased the risk of symptomatic TE, as demonstrated by the following p-values: DVT (p=.66), PE (p=.65), and DVT/PE (p=.459). Similarly, a history of TE\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003edid not affect the subsequent incidence of symptomatic TE following surgical resection of GBM: DVT (p=.17), PE (p=.154), and DVT/PE (p=.121).\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eProcedure specific risk factors\u003c/u\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eProcedure-specific factors also played a significant role in the development of symptomatic TE. Longer surgeries were associated with a higher risk of symptomatic PE. Patients who developed symptomatic PE had a median surgical time of 249 minutes compared to 190 minutes for the overall cohort (p=.002). Additionally, surgeries in patients with combined symptomatic DVT/PE were on average 43 minutes longer than those without symptomatic thromboembolic complications (p=.011).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIntraoperative blood loss was another significant risk factor. Patients who developed symptomatic PE lost a median of 300mL of blood compared to 150mL in patients without symptomatic PE (p=.002). Similarly, patients with combined symptomatic DVT/PE experienced greater blood loss (median 200mL; p=.012).\u003c/p\u003e\n \u003cp\u003eThe majority of patients (76.8%) were positioned supine during surgery, followed by, prone (14.9%), lateral (8.1%) and Trendelenburg position (0.1%). However, the small sample sizes of the individual subgroups limited meaningful statistical evaluation of these data.\u003c/p\u003e\n \u003cp\u003e\u003cu\u003eIndependent predictors for symptomatic TE\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eMultivariate binary logistic regression analysis was performed to identify independent predictors of symptomatic TE (table 3). The prophylaxis group was determined to be an independent predictor for the occurrence of symptomatic TE. Specifically, patients in the enoxaparin-only group exhibited a significantly higher risk of symptomatic TE compared to the other groups (hazard ratio (HR) 0.312, 95% CI 0.116-0.842; p=.022).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAdditionally, diabetes mellitus emerged as a patient-specific independent risk factor for the occurrence of\u0026nbsp;symptomatic\u0026nbsp;PE (p=.007, HR 3.6, 95% CI 1.4\u0026ndash;9.2) and combined\u0026nbsp;symptomatic\u0026nbsp;DVT/PE (p=.009, HR 3.0, 95% CI 1.3\u0026ndash;6.8).\u003c/p\u003e\n \u003cp\u003eAmong the procedure-specific factors, longer\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003esurgery duration was identified as an independent predictor for symptomatic DVT (p=.047, HR 2.5, 95% CI 1.0\u0026ndash;6.4), symptomatic PE (p=.045, HR 2.9, 95% CI 1.0\u0026ndash;8.4), combined symptomatic DVT/PE (p=.039, HR 2.6, 95% CI 1.6\u0026ndash;6.5). Similarly, increased blood loss was a significant predictor for the occurrence of symptomatic PE (p=.03, HR 0.35, 95% CI 0.14\u0026ndash;0.9).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe relationship between GBM and thrombosis has become increasingly well-understood through ongoing research. This study emphasizes the need to differentiate between perioperative prophylaxis strategies for GBM patients. Our findings indicate that GBM patients treated solely with enoxaparin had a significant higher risk for symptomatic TE compared to those treated with certoparin or a combination of enoxaparin and IPS. Similar to other studies, we found that combining LMWH with IPS yielded the best patient outcome [26]. As there are currently no specific guidelines on the preferred LMWH, and given the efficacy highlighted in our study, further research is needed to fully understand the varying impact of different agents.\u003c/p\u003e\n\u003cp\u003eAdditionally, factors such as age above 65, pre-existing comorbidities like diabetes and hypertension, longer surgery duration (\u0026gt;200min) and higher intraoperative blood loss (\u0026gt;200mL) were identified as significant risk factors for symptomatic TE (table 4). Conversely, factors such as sex, epilepsy, atrial fibrillation, and a history of TE were not found to increase the risk.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFrom our study, three key points emerge:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cu\u003eLow molecular weight heparins = “same, same but different”?\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eWhile general guidelines exist for postoperative thromboprophylaxis in cancer patients, the selection of a specific LMWH remains a subject of ongoing debate [5,19,20]. Increasing evidence in neurosurgery supports the use of LMWHs, which do not significantly increase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ethe risk of postoperative intracranial hemorrhage when doses are controlled (\u0026lt;4000I U/day) and administrated the day after surgery [18,27]. To date, no clear recommendations exist regarding the most appropriate LMWH, such as certoparin, enoxaparin, dalteparin or nadroparin, and whether their effectiveness in reducing symptomatic TE varies. Given that LMWHs are derived from different manufacturing processes, resulting in varied molecular compositions, it is unsurprising that they may differ in function. LMWHs share a mechanism of action that involves antithrombin-mediated inhibition of factor Xa, along with several pleiotropic effects, but no two LMWHS are exactly alike [28–30].\u003c/p\u003e\n\u003cp\u003eFor example, enoxaparin products like Clexane (est. 1994) and Inhixa (est. 2017), though both classified as LMWHs, differ in their properties due to their unique production processes. While marketed as biosimilars, these products are not identical. Inhixa, introduced in 2017 under revised European Medicines Agency (EMA) approval processes [31], was approved through a simplified regulatory process as part of EU harmonization efforts, despite being a complex mixture of biogenic origin. The potential clinical value of a biosimilar can be assessed using the System of Objectified Judgement Analysis (SOJA). In this case, the total score would currently fall significantly below 1000 points, the target value, due to the lack of clinical data [32]. This raises concerns about clinical efficacy and bioequivalence, even between Inhixa and Clexane, both of which are enoxaparin. Due to the varying chemical modifications introduced by each manufacturing process, LMWHs from different manufacturers are not identical chemical entities [28,33,34]. Imberti et al. recommended in their review from 2017 to not follow the changed EMA approval of enoxaparin biosimilars, due to serious concerns regarding efficacy and safety [33]. Studies have shown that Inhixa has only 85% of the tissue factor pathway inhibitor (TFPI) activity of Clexane, suggesting potential differences in therapeutic efficacy [22,29]. On the other hand, in 2020, Fantoni et al. conducted a retrospective observational report on the safety\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eand efficacy of biosimilar enoxaparin in 189 medical and 192 general surgical patients. All surgical patients underwent major abdominal surgery, again highlighting the lack of representation of neurosurgical patients, who were excluded from the studies.\u003c/p\u003e\n\u003cp\u003eFantoni et al. found that the incidence of bleeding and VTE was 0.5%, which is comparable to the estimated rates in their literature analysis [35]. Further research is needed to fully understand these differences and their clinical implications, and to re-evaluate and discuss the changes in the EMA approval process. We have not yet compared our subgroups based on Inhixa or Clexane, but this will be an interesting target for the future. Our study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003efound that certoparin was more effective than enoxaparin, raising questions about possible pharmacokinetic differences despite their apparently similar properties such as half-life and bioavailability. Further research is needed to determine whether these differences impact patient outcomes, and ongoing studies should explore the bioequivalence and pharmacokinetics of biosimilars like Inhixa and Clexane.\u0026nbsp;\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cu\u003eIntermittent Pneumatic Stockings\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOur finding suggests that patients receiving certoparin had a comparable low incidence of symptomatic TE, similar to those receiving enoxaparin in combination with IPS, but those treated with enoxaparin without IPS exhibited significantly higher symptomatic TE incidence. This highlights the potential importance of IPS in thromboprophylaxis. While current S3 guideline recommend the use of IPS, no studies have specifically evaluated the combination of IPS with different LMWHs to determine which combination offers the best protection against thromboembolic complications [18,19,21,36].\u003c/p\u003e\n\u003cp\u003eFurther studies are required to investigate whether adding IPS to certoparin or even using IPS alone could lead to similarly effective outcomes. Understanding the interplay between these interventions could refine prophylactic strategies, particularly for high-risk patients.\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cu\u003ePredictive score\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe widely used Khorana score for predicting symptomatic TE in cancer patients has been shown to be inapplicable to patients with GBM\u0026nbsp;[37]. While highly sensitive (98%) for predicting symptomatic TE, its specificity in GBM populations is low (5,6%), as Yust-Katz et al. showed 2014 in their clinical study (n=418)\u0026nbsp;[38]. Khorana himself acknowledged that the data set used to develop the Khorana Score included only a small number of brain tumor patients (n=4). In addition, patients with poor performance status were underrepresented in the cohort, which may limit the applicability of the score to these populations\u0026nbsp;[39]. The Khorana score is made up of the following parameters: 1) cancer type; 2) pre-chemo platelet count; 3) hemoglobin level; 4) pre-chemo leukocyte count; 4) body-mass-index. \u0026nbsp;In 2022, Bell Burdett et al. presented a new predictive time-to-event-model that incorporates additional parameters, to more accurately reflect the complex nature of GBM: 1) history of TE; 2) hypertension; 3) asthma; 4) white blood cell count; 5) WHO tumor grade; 6) patient age; 7) body-mass-index. They created a web based TE prediction tool that was validated in two separate cohorts\u0026nbsp;[40]. Our study confirmed the risk factors hypertension and patients age, but also integrated further risk factors, such as surgery duration and intraoperative blood loss, that could augment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBell's score by incorporating procedure-specific elements. Future efforts should aim to integrate these factors into a more comprehensive and clinically practical scoring system\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u0026nbsp;Limitations\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations, including a relatively small sample size, especially for patients with symptomatic TE, which may contribute to variability in the statistical analysis. The single-center design and potential reporting bias (underreporting) limit the generalizability of the findings. Additionally, TE were identified solely based on patient complaints, and using a standardized screening instrument to assess typical TE symptoms in each patient would have been beneficial.\u003c/p\u003e\n\u003cp\u003eA comparison group for the combination of certoparin and IPS was not feasible due to supply issues with certoparin starting in 2019. Our objective was to compare our in-house prophylaxis measures with each other and to identify risk factors. We were able to achieve meaningful results in this regard. Given the medical context, we focused on clinical parameters. Another improvement would be the collection of laboratory markers for coagulation factors to compare the performance of Khorana’s and Bell’s predictive models. This would provide insights into\u0026nbsp;\u003c/p\u003e\n\u003cp\u003etheir accuracy and applicability to this specific patient population. However, this study offers clinically relevant findings that can help develop more precise risk profiles for GBM patients in future research. An easy-to-use predictive model would be beneficial for better assessing individual patient risk and tailoring treatment strategies. Further investigation into the pharmacokinetic differences between various LMWHs and the bioequivalence of biosimilars like Inhixa and Clexane remains crucial.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study highlights the importance of selecting the right thromboprophylaxis strategy for GBM patients to minimize postoperative complications. Our findings contribute to optimizing postoperative care and provide valuable directions for future research on personalized thromboprophylaxis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting Interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthor contributions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by WHP and EW. The first draft of the manuscript was written by EW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eData Availability\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eEthics approval\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Hospital of Dresden (\u003c/em\u003eEK63022018).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eInformed Consent Statement\u003c/u\u003e\u003cbr\u003e\u0026nbsp;All patients provided written informed consent for the use of their clinical data for research purposes as part of the treatment contract with the University Hospital Dresden.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerlay, J., Parkin, D. M. \u0026amp; Steliarova-Foucher, E. Estimates of cancer incidence and mortality in Europe in 2008. \u003cem\u003eEur. J. Cancer M\u0026auml;rz\u003c/em\u003e. \u003cb\u003e46\u003c/b\u003e (4), 765\u0026ndash;781 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeAngelis, L. M. Brain Tumors. \u003cem\u003eN Engl. J. 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Oncol. 10 Februar\u003c/em\u003e. \u003cb\u003e38\u003c/b\u003e (5), 496\u0026ndash;520 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS3-Leitlinie Prophylaxe der ven\u0026ouml;sen Thromboembolie (VTE). 2. komplett \u0026uuml;berarbeitete Auflage. AWMF Leitlinien-Regist Nr 003001. 15. ;Oktober (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003einhixa-epar-product. -information_en.pdf [Internet]. Verf\u0026uuml;gbar unter: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ec.europa.eu/health/documents/community-register/2017/20170717138295/anx_138295_de.pdf\u003c/span\u003e\u003cspan address=\"https://ec.europa.eu/health/documents/community-register/2017/20170717138295/anx_138295_de.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMono-Embolex\u0026reg; 3000 I.E. Prophylaxe Sicherheitsspritze. ; (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaabe, A., Gerlach, R., Zimmermann, M. \u0026amp; Seifert, V. Praxis der Thromboseprophylaxe in der Neurochirurgie: Ergebnisse einer Umfrage in Deutschland. \u003cem\u003eZentralblatt F\u0026uuml;r Neurochir.\u003c/em\u003e \u003cb\u003e61\u003c/b\u003e (02), 103\u0026ndash;110 (2000).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurtoglu, M. et al. u. a. Venous Thromboembolism Prophylaxis after Head and Spinal Trauma: Intermittent Pneumatic Compression Devices Versus Low Molecular Weight Heparin. \u003cem\u003eWorld J. Surg. August\u003c/em\u003e. \u003cb\u003e28\u003c/b\u003e (8), 807\u0026ndash;811 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlshehri, N. et al. u. a. Venous thromboembolism prophylaxis in brain tumor patients undergoing craniotomy: a meta-analysis. \u003cem\u003eJ. Neurooncol Dezember\u003c/em\u003e. \u003cb\u003e130\u003c/b\u003e (3), 561\u0026ndash;570 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDasgupta, P. \u0026amp; Rousseau, J. F. Clinical and molecular determinants of bleeding-related adverse outcomes in high-grade glioma. \u003cem\u003eJ. Neurooncol Februar\u003c/em\u003e. \u003cb\u003e166\u003c/b\u003e (3), 569\u0026ndash;574 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalenga, J., Jackson, C. \u0026amp; Kessler, C. Low Molecular Weight Heparins Differ Substantially: Impact on Developing Biosimilar Drugs. \u003cem\u003eSemin Thromb. Hemost. April\u003c/em\u003e. \u003cb\u003e37\u003c/b\u003e (03), 322\u0026ndash;327 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLipp, H. P. \u0026Auml;hnlich, aber nicht gleich. \u003cem\u003eDtsch. Apoth Ztg. 20 Juli\u003c/em\u003e ;(29):48. (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFareed, J. et al. u. a. Pharmacodynamic and Pharmacokinetic Properties of Enoxaparin. \u003cem\u003eClin. Pharmacokinet. 1 Oktober\u003c/em\u003e. \u003cb\u003e42\u003c/b\u003e (12), 1043\u0026ndash;1057 (2003).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003einhixa-epar-summary-public_en.pdf [Internet]. European Medicines Agency. [zitiert 12. September 2024]. Verf\u0026uuml;gbar unter: (2022). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ema.europa.eu/en/documents/overview/inhixa-epar-summary-public_en.pdf\u003c/span\u003e\u003cspan address=\"https://www.ema.europa.eu/en/documents/overview/inhixa-epar-summary-public_en.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanknegt, R. et al. System of Objectified Judgement Analysis (SOJA) as a tool in rational and transparent drug-decision making. \u003cem\u003eExpert Opin. Pharmacother Oktober\u003c/em\u003e. \u003cb\u003e8\u003c/b\u003e (sup1), S5\u0026ndash;14 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImberti, D., Marietta, M., Polo Friz, H. \u0026amp; Cimminiello, C. The introduction of biosimilars of low molecular weight heparins in Europe: a critical review and reappraisal endorsed by the Italian Society for Haemostasis and Thrombosis (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV). \u003cem\u003eThromb. J. Dezember\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e (1), 13 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFareed, J., Jeske, W., Hoppensteadt, D., Clarizio, R. \u0026amp; Walenga, J. M. Are the available low-molecular-weight heparin preparations the same? \u003cem\u003eSemin Thromb. Hemost.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e (Suppl 1), 77\u0026ndash;91 (1996).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFantoni, C. et al. Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients. \u003cem\u003eIntern. Emerg. Med. Juni\u003c/em\u003e. \u003cb\u003e16\u003c/b\u003e (4), 933\u0026ndash;939 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurpie, A. G., Hirsh, J., Gent, M., Julian, D. \u0026amp; Johnson, J. Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control. \u003cem\u003eArch. Intern. Med.\u003c/em\u003e \u003cb\u003e149\u003c/b\u003e (3), 679\u0026ndash;681 (M\u0026auml;rz 1989).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang, X. et al. u. a. External validation of the Khorana score for the prediction of venous thromboembolism in cancer patients: A systematic review and meta-analysis. \u003cem\u003eInt. J. Nurs. Stud. November\u003c/em\u003e. \u003cb\u003e159\u003c/b\u003e, 104867 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYust-Katz, S. et al. u. a. Venous thromboembolism (VTE) and glioblastoma. \u003cem\u003eJ. Neurooncol August\u003c/em\u003e. \u003cb\u003e124\u003c/b\u003e (1), 87\u0026ndash;94 (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhorana, A. A., Kuderer, N. M., Culakova, E., Lyman, G. H. \u0026amp; Francis, C. W. Development and validation of a predictive model for chemotherapy-associated thrombosis. \u003cem\u003eBlood 15 Mai\u003c/em\u003e. \u003cb\u003e111\u003c/b\u003e (10), 4902\u0026ndash;4907 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBell Burdett, K. VTE Prediction for Pateients with Glioma [Internet]. [zitiert 18. September 2024]. Verf\u0026uuml;gbar unter: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://kbellburdett.shinyapps.io/GliomaPredictVTE/\u003c/span\u003e\u003cspan address=\"https://kbellburdett.shinyapps.io/GliomaPredictVTE/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 1:\u003c/u\u003e\u003c/strong\u003e\u003cu\u003e\u0026nbsp;Demographic and clinical characteristics of the study cohort\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"538\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCharacteristic\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eAge in years, median\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e64 (20-94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eFemale sex, n (%)\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e264 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cp\u003e\u003cem\u003eComorbidities, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eEpilepsy\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eArterial hypertension\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eDiabetes mellitus 1 / 2\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eChronic heart disease\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eAtrial fibrillation\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003ePrior thromboembolic event\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e301 (43.3)\u003c/p\u003e\n \u003cp\u003e415 (59.7)\u003c/p\u003e\n \u003cp\u003e106 (15.3)\u003c/p\u003e\n \u003cp\u003e46 (6.6)\u003c/p\u003e\n \u003cp\u003e53 (7.6)\u003c/p\u003e\n \u003cp\u003e48 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cp\u003e\u003cem\u003eClinical parameters, median\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eDuration of surgery, minutes\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eBlood loss, milliliter\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e191\u003c/p\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66.6048%;\"\u003e\n \u003cp\u003e\u003cem\u003eThromboembolic complications, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eDeep vein thrombosis\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003ePulmonary embolism\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eDeep vein thrombosis/Pulmonary embolism\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.3952%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (3)\u003c/p\u003e\n \u003cp\u003e20 (2.9)\u003c/p\u003e\n \u003cp\u003e28 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eTable 2:\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003cu\u003eDemographic and clinical parameters stratified by thromboembolic events\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"599\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCharacteristic\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTE positive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTE negative\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eMedian age, year (IQR)\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cem\u003eSex, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (2.3)\u003c/p\u003e\n \u003cp\u003e22 (5.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e257 (97.7)\u003c/p\u003e\n \u003cp\u003e409 (94.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cem\u003eComorbidities, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eHypertonus (414)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 22 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 392 (94.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eChronic heart disease (46)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e4 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e42 (91.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eEpilepsy (301)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e10 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e291 (96.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.442\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eDiabetes (106)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e10 (9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e96 (90.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eAtrial fibrillation (52)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e3 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e49 (94.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cul\u003e\n \u003cli\u003ePrior TE (48)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e4 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e44 (91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cem\u003eProphylaxis group, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eCertoparin\u003c/li\u003e\n \u003cli\u003eEnoxaparin\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEnoxaparin + IPS\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (2.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;14 (8.6)\u003c/p\u003e\n \u003cp\u003e6 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e296 (97.4)\u003c/p\u003e\n \u003cp\u003e149 (91.4)\u003c/p\u003e\n \u003cp\u003e221 (97.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cem\u003eBlood loss\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMedian blood loss, mL\u003c/li\u003e\n \u003cli\u003eBlood loss \u0026gt; 200mL, n (%)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003cp\u003e13 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e150\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e190 (93.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;.012\u003c/p\u003e\n \u003cp\u003e.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.796%;\"\u003e\n \u003cp\u003e\u003cem\u003eDuration of surgery\u003c/em\u003e\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMedian duration, min\u003c/li\u003e\n \u003cli\u003eDuration \u0026gt; 200min, n (%)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003cp\u003e20 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.0769%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e189\u003c/p\u003e\n \u003cp\u003e291 (93.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.0502%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.011\u003c/p\u003e\n \u003cp\u003e.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: TE, thromboembolic event; IPS, intermittent pneumatic stockings; mL, milliliters; min, minutes\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 3:\u003c/u\u003e\u003c/strong\u003e\u003cu\u003e\u0026nbsp;Results of the multivariate analysis: Independent, prognostic risk factors\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"596\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDVT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSig (p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSig (p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDVT/PE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSig (p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePatient specific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDM 1/2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eProcedure specific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery duration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eloss\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eProphylaxis\u003c/p\u003e\n \u003cp\u003especific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnoxaparin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: TE, thromboembolic event; DVT, deep vein thrombosis; PE, pulmonary embolism; DM 1/2, diabetes mellitus 1/2; Sig (p), significance (p-value); HR, hazard ratio.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 4:\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003cu\u003eRisk factors for thromboembolic events in patients with glioblastoma\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"608\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 203px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient specific\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 203px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProcedure specific\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 203px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProphylaxis specific\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 203px;\"\u003e\n \u003cul\u003e\n \u003cli\u003eAge \u0026gt; 65years\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCHD\u003c/li\u003e\n \u003cli\u003eDM \u0026frac12;\u003c/li\u003e\n \u003cli\u003eHypertension\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 203px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eBlood loss\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026gt; 200mL\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eSurgery duration \u0026gt;200min\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMonotherapy with enoxaparin\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CHD, chronic heart disease; DM 1/2, diabetes mellitus type \u0026frac12;; mL, milliliter; min, minutes, IPS, intermittent pneumatic stockings.\u003c/p\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Thromboembolic events (TE), Glioblastoma, Anticoagulant treatments, Postoperative complications, Risk factors ","lastPublishedDoi":"10.21203/rs.3.rs-6448196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6448196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Thromboembolic events (TE) are serious complications following glioblastoma (GBM) resection. This retrospective study analyzed 695 GBM patients (2017–2022, University Hospital Dresden) to assess the impact of different anticoagulant regimens—certoparin, enoxaparin, and enoxaparin with intermittent pneumatic stockings (IPS)—along with patient comorbidities, on TE incidence. Overall, 28 patients (4%) developed TE. The highest combined incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in the enoxaparin group (8.6%), followed by certoparin (6.9%) and enoxaparin + IPS (2.6%) (p = .003). Increased PE risk was associated with longer surgery duration (median 249 vs. 190 min; p = .002), greater intraoperative blood loss (300 vs. 150 mL; p = .002), and older age (\u003e65 years, p = .043). Comorbidities such as diabetes (p = .005) and coronary heart disease (p = .037) were also linked to elevated TE risk. Multivariate analysis identified enoxaparin alone as an independent risk factor (HR 0.312; CI 0.116–0.842; p = .022). Patients with PE or DVT had surgeries that were on average 45 minutes longer and involved higher blood loss. GBM patients treated with enoxaparin alone have a significant higher risk for TE compared to treatment with certoparin or the combination of enoxaparin with IPS. Additionally, the duration of surgery, patient age and comorbidities significantly influence the risk of postoperative TE.","manuscriptTitle":"Impact of Thromboprophylaxis on Postoperative Complications in Glioblastoma Patients: Findings From a Prospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 02:23:53","doi":"10.21203/rs.3.rs-6448196/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"305571354242215403707424556863758210457","date":"2025-05-14T09:13:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133402157493945207511977657400697565406","date":"2025-05-09T10:26:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317524736920507246698145435467059611275","date":"2025-05-08T05:13:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-07T23:29:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-07T23:26:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-23T16:27:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-23T08:28:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-14T17:09:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7b496667-ba03-4dfe-a906-58b756227bd5","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":48482468,"name":"Health sciences/Medical research/Outcomes research"},{"id":48482469,"name":"Health sciences/Oncology/Cancer"},{"id":48482470,"name":"Health sciences/Oncology/Surgical oncology"},{"id":48482471,"name":"Health sciences/Medical research"},{"id":48482472,"name":"Health sciences/Oncology"},{"id":48482473,"name":"Health sciences/Risk factors"},{"id":48482474,"name":"Health sciences/Diseases/Cancer"}],"tags":[],"updatedAt":"2025-07-07T16:08:42+00:00","versionOfRecord":{"articleIdentity":"rs-6448196","link":"https://doi.org/10.1038/s41598-025-07899-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-01 15:58:43","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2025-05-15 02:23:53","video":"","vorDoi":"10.1038/s41598-025-07899-2","vorDoiUrl":"https://doi.org/10.1038/s41598-025-07899-2","workflowStages":[]},"version":"v1","identity":"rs-6448196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6448196","identity":"rs-6448196","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}