Revision rate and postoperative volume development of chronic subdural hematomas after burr hole craniotomy in combination with tranexamic acid vs. surgery alone – a single-center propensity score- matched analysis

Revision rate and postoperative volume development of chronic subdural hematomas after burr hole craniotomy in combination with tranexamic acid vs. surgery alone – a single-center propensity score- matched analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Revision rate and postoperative volume development of chronic subdural hematomas after burr hole craniotomy in combination with tranexamic acid vs. surgery alone – a single-center propensity score- matched analysis Magnus Scheer, Hanno Witte, Paulina Guenzerodt, Vanessa Beuchel, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9361375/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Chronic subdural hematoma (cSDH) is a common intracranial hemorrhage in elderly patients and is associated with substantial postoperative recurrence rates. Tranexamic acid (TXA) has been proposed as an adjuvant therapy to reduce recurrence by targeting hyperfibrinolysis; however, its efficacy and impact on hematoma volume evolution remain controversial. Methods We performed a retrospective cohort study of adult patients who underwent burr-hole evacuation with subdural drainage for cSDH at a single neurosurgical center between 2012 and 2024. Patients receiving postoperative TXA within 48 hours for at least 30 days were compared with patients treated surgically without TXA. Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was revision surgery for recurrent cSDH within 3 months. Secondary outcomes included postoperative hematoma volume evolution and all-cause mortality. Results After matching, 73 patients were included in each group with well-balanced baseline characteristics. Revision surgery within 90 days occurred less frequently in the TXA group compared with controls (8.2% vs. 19.2%; OR 0.40, 95% CI 0.14–1.12; p = 0.042), although the confidence interval marginally crossed unity, indicating limited precision. Median time to revision was 8 days in the TXA group and 11 days in the control group. Mortality was numerically lower in the TXA group, with no deaths observed, compared with one death (1.4%) in the control group. Preoperative, postoperative, and one-month follow-up hematoma volumes were comparable between groups, and no significant difference in absolute volume reduction was detected. Conclusion Postoperative adjuvant TXA therapy after surgical evacuation of cSDH was associated with a lower rate of recurrence requiring revision surgery, without an observed increase in mortality; however, the confidence interval marginally crossed unity, and the findings should be regarded as hypothesis-generating. TXA did not significantly influence short-term hematoma volume reduction. Prospective randomized studies are needed to confirm these findings and define optimal dosing strategies. Tranexamic acid Chronic Subdural hematoma Recurrence after surgery Propensity score matching Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Chronic subdural hematoma (cSDH) represents one of the most common traumatic intracranial hemorrhages in Western industrialized countries [ 28 ]. It is defined as a persistent accumulation of hemorrhagic to serous fluid within the subdural space, typically resulting from a mild traumatic brain injury that occurred several weeks earlier. The reported incidence (1.7–20.6 per 100,000 inhabitants) increases significantly with age, posing a growing challenge in the context of ongoing demographic change [ 4 ]. The pathophysiology of cSDH is complex and cannot be explained solely by the accumulation of blood following rupture of bridging veins. Rather, the underlying mechanism is thought to involve injury to the dural border cell layer, a highly specialized connective tissue cell layer located between the dura mater and the arachnoid mater. Disruption of this layer initiates a local inflammatory response, which, through the induction of angiogenesis, leads to the formation of pathological, thin-walled capillaries that are prone to rupture and cause recurrent microhemorrhages. In parallel, plasminogen-activated hyperfibrinolysis of the hematoma content—considered an acute-phase reaction—impairs physiological clot formation [ 5 , 9 ]. This results in a self-perpetuating cycle of cellular proliferation, angiogenesis, hyperfibrinolysis, and recurrent bleeding, ultimately driving the progressive enlargement of the hematoma [ 3 , 21 ]. Treatment strategies for cSDH range from conservative management in asymptomatic patients with small hematomas (wait-and-watch strategy) to surgical decompression in cases of radiologically confirmed brain compression accompanied by neurological deficits [ 11 ]. Surgical approaches include burr-hole trephination or craniotomy with drainage [ 10 ]. Regardless of the surgical technique employed, relatively high recurrence rates (2.3%–38.7%) requiring revision surgery have been reported [ 17 , 22 ]. In light of these recurrence rates, adjunctive conservative treatment strategies have gained increasing attention [ 8 ], with particular focus on targeting hyperfibrinolysis. Several studies investigating perioperative pharmacological therapy have reported promising results with tranexamic acid (TXA) [ 6 , 12 , 13 , 14 , 18 , 23 , 26 , 27 , 30 , 31 ]. As a specific antifibrinolytic agent, TXA inhibits plasminogen activation and thereby suppresses hyperfibrinolysis within the hematoma, potentially preventing re-expansion of cSDH through the reduction of recurrent microbleeding [ 20 ]. However, this therapeutic approach remains controversial, as several studies have also reported no significant reduction in recurrence rates or even increased mortality associated with adjuvant TXA therapy [ 2 , 24 ]. The aim of the present study was to evaluate the efficacy of tranexamic acid with regard to reducing postoperative recurrence rates as well as postoperative hematoma volume reduction following surgical evacuation of chronic subdural hematomas. Methods and materials Study Population and Inclusion Criteria: We retrospectively analyzed patients treated for chronic subdural hematoma (cSDH) at the Department of Neurosurgery, German Armed Forces Hospital in Ulm, between 2012 and 2024. All patients aged ≥ 18 years who underwent unilateral or bilateral hematoma evacuation via burr-hole craniotomy with placement of a subdural drain during this period were eligible for inclusion. Patients with incomplete clinical data, including missing or incomplete cross-sectional imaging, as well as patients who developed an acute subdural hematoma due to immediate postoperative rebleeding, were excluded. Two cohorts were defined: an intervention group comprising patients who received oral tranexamic acid (TXA), initiated within two days after surgical evacuation of cSDH and continued for a minimum of 30 days, without any preceding intravenous loading dose or transition regimen, and a control group consisting of patients who underwent surgical treatment without adjuvant therapy. TXA was introduced at our institution in 2012 as an adjunctive option for recurrence prophylaxis based on emerging evidence in the literature. Throughout the study period, surgical and postoperative management of cSDH remained unchanged. TXA use was at the discretion of the treating neurosurgeon and was not governed by a predefined institutional protocol. The only contraindications were known hypersensitivity and active thromboembolic disease. No standardized dose adjustments were applied based on renal function. Thromboelastography was not used. This cohort study was approved by the Ethics Committee of Ulm University on October 10, 2023 (approval number: 311/23) and was conducted in accordance with the Declaration of Helsinki as revised in 2008. Study Outcomes: The primary outcome was the need for revision surgery due to recurrent hematoma within three months following the initial operation. Secondary outcomes included postoperative volume evolution of the residual hematoma in the immediate postoperative period and at one-month follow-up, as well as overall mortality in both groups during a total observation period of three months. Statistical Analysis: Statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) with the packages MatchIt, tableone, pROC, effsize, dplyr, tidyr and ggplot2 . To account for baseline imbalances between patients treated with tranexamic acid (TXA) and those without TXA, we applied propensity score matching using the MatchIt package. The propensity score was estimated in a logistic regression model with TXA exposure as the dependent variable and age, hematoma architecture classified according to the Nakaguchi classification [ 19 ], and pre-existing anticoagulation as covariates. Patients were then matched in a 1:1 ratio using optimal matching based on the logit of the propensity score. Covariate balance before and after matching was assessed with the tableone package by comparing summary statistics and calculating standardized mean differences for all baseline variables. Group comparisons between TXA and no-TXA patients in the matched cohort were performed using CreateTableOne , which employs χ² tests or Fisher’s exact tests for categorical variables and Student’s t tests or Wilcoxon rank-sum tests for continuous variables, as appropriate. The primary outcome was the need for surgical revision. The association between TXA use and revision surgery was evaluated in the matched sample using contingency tables and Fisher’s exact test. Additionally, a sensitivity analysis was performed after exclusion of all patients receiving oral anticoagulation therapy to assess the robustness of the primary findings. Recurrence rates were compared using Fisher’s exact test, and odds ratios with 95% confidence intervals were calculated. This analysis was exploratory and not powered for subgroup comparisons. To determine an optimal hematoma volume threshold for predicting revision, receiver operating characteristic (ROC) analysis was conducted with the pROC package, using revision (yes/no) as the binary outcome and preoperative hematoma volume as the continuous predictor. The optimal cut-off was derived from the Youden index. To quantify patients with a hematoma volume exceeding the ROC-based cut-off, a dichotomous event variable was created. Group comparisons were performed using a two-sided Fisher’s exact test due to low event rates. Changes in hematoma volume over time (VolDiff: preoperative to postoperative change; VolDiff2: postoperative to 1-month follow-up change) were summarized by means and standard deviations within each group and compared between TXA and no-TXA patients using both Student’s t tests and Wilcoxon rank-sum tests. Effect sizes for volume reduction were quantified using Cohen’s d with the effsize package. Unless stated otherwise, all tests were two-sided and a p-value < 0.05 was considered statistically significant. Results Patient characteristics: Between January 2012 and October 2024, a total of 236 patients with chronic subdural hematoma (cSDH) were treated by burr-hole trephination with placement of a subdural drain at the Department of Neurosurgery, Bundeswehr Hospital Ulm. Of these, 216 patients met the inclusion criteria for the retrospective cohort analysis. Within the study population, 73 patients received adjuvant oral therapy with tranexamic acid (TXA), initiated within 48 hours after surgery and continued for a minimum of 30 days. The remaining 143 patients underwent standard treatment consisting of surgical hematoma evacuation without additional therapy. (Fig. 1 ) In the unmatched cohort, significant differences between groups were observed, particularly with respect to the use of direct oral anticoagulants (DOACs) (35 vs. 3 patients, p < 0.001). After propensity score matching, 73 patients remained in each group, with adequate balance of the selected covariates. Specifically, the use of DOACs (3 vs. 3, p = 1.000), Nakaguchi classification (type I: 38 vs. 38; type II: 7 vs. 5; type III: 4 vs. 4; type IV: 24 vs. 26; p = 0.937), history of hypertension (34 vs. 34, p = 1.000), and use of platelet aggregation inhibitors (13 vs. 13, p = 1.000) were evenly distributed between the groups. No statistically significant differences in baseline characteristics were observed after matching. Following propensity score matching, age and sex distributions were comparable between the TXA and control groups. In the TXA group, 50 patients were male (68.5%) and 23 were female (31.5%), whereas in the non-TXA group, 59 patients were male (80.8%) and 14 were female (19.2%); the difference in sex distribution was not statistically significant (p = 0.128). Mean age was 72.90 years in the TXA group and 73.29 years in the control group (p = 0.855), indicating successful balancing of these baseline characteristics through matching. (Table 1 ) In the TXA group, the mean daily dose of tranexamic acid was 1,226 mg administered for a minimum duration of 30 days (range: 500–2,000 mg). Forty-five patients (61.6%) received a total daily dose of 1,500 mg, divided into two or three administrations. Fourteen patients (19.2%) received 500 mg, four patients (5.5%) received 750 mg, eight patients (11.0%) received 1,000 mg, and two patients (2.7%) received 2,000 mg as the total daily dose. Table 1 Patient characteristics and results pre- and post-matching, CKD, chronic kidney disease; PAI, platelet aggregation inhibition, TXA, tranexamic acid, Preop, preoperativ Characteristics All patients Matched pairs No TXA (n = 143) TXA (n = 73) P value No TXA (n = 73) TXA (n = 73) P value Sex: n (%) m 112(78.3) 50 (68.5) 0.158 59 (80.8) 50 (68.5) 0.128 f 31 (21.7) 23 (31.5) 14 (19.2) 23 (31.5) Age (median) 74.99 72.90 0.263 73.29 72.90 0.855 Nakaguchi Score: n (%) 1 81 (56.6) 38 (52.1) 0.117 38 (52.1) 38 (52.1) 0.937 2 12 (8.4) 5 (6.8) 7 (9.6) 5 (6.8) 3 18 (12.6) 4 (5.5) 4 (5.5) 4 (5.5) 4 32 (22.4) 26 (35.6) 24 (32.9) 26 (35.6) CKD: n (%) 1 25 (38.5) 15 (22.7) 0.197 25 (39.7) 15 (22.7) 0.172 2 20 (30.8) 32 (48.5) 19 (30.2) 32 (48.5) 3a 13 (20.0) 11 (16.7) 12 (19.0) 11 (16.7) 3b 4 (6.2) 6 (9.1) 4 (6.3) 6 (9.1) 4 3 (4.6) 2 (3.0) 3 (4.8) 2 (3.0) Anticoagulation: n (%) 35 (24.5) 3 (4.1) < 0.001 3 (4.1) 3 (4.1) 1.000 PAI: n(%) 22 (30.1) 13 (17.8) 0.121 13 (17.8) 13 (17.8) 1.000 Diabetes mellitus: n (%) 26 (18.2) 7 (9.6) 0.144 14 (19.2) 7 (9.6) 0.157 Hypertension: n (%) 82 (57.3) 34 (46.6) 0.175 34 (46.6) 34 (46.6) 1.000 Seizure: n (%) 7 (4.9) 1 (1.4) 0.359 3 (4.1) 1 (1.4) 0.612 Localization: n (%) Bilateral 23 (16.1) 14 (19.2) 0.743 12 (16.4) 14 (19.2) 0.790 Left 68 (47.6) 31 (42.5) 35 (47.9) 31 (42.5) Right 52 (36.4) 28 (38.4) 26 (35.6) 28 (38.4) Hematoma volume: ml (median) preoperative 100 97 0.840 94 104 0.949 postoperative 60 58 0.881 57 60 0.637 1 month postoperative 35 20 0.107 25 20 0.232 Decrease preop to 1 month postsurgical 70 74 0.381 68 85 0.361 Revision: n (%) 23 (16.1) 6 (8.2) 0.178 14 (19.2) 6 (8.2) 0.042 Complications: n (%) Death events 5 (3,5) 0 (0) 1 (1.4) 0 (0) 0.0175** Neurologic impairment* 1 (0) 0 (0) 0 (0) 0 (0) Surgery related 1 (0) 0 (0) 0 (0) 0 (0) Others 3 (2,1) 0 (0) 1 (1,4) 0 (0) * new after surgery ** overall complications Outcome Measures: Primary Outcome Before propensity score matching, the 90-day revision surgery rate was higher in the control group than in the TXA group (16.1% vs. 8.2%; OR = 0.452; 95% CI: 0.175–1.65), without reaching statistical significance (p = 0.178). (Fig. 2 ) After matching, the revision rate was higher in the control group compared with the TXA group (19.2% vs. 8.2%; OR = 0.400; 95% CI: 0.143–1.118; p = 0.042). In the analysis after exclusion of all patients receiving oral anticoagulation therapy, recurrence occurred in 7.1% of TXA-treated patients and in 19.4% of controls (OR 0.37; 95% CI 0.10–1.12; p = 0.068). Median time to revision surgery was 11 days (range: 1–91 days) in the control group and 8 days (range: 8–14 days) in the TXA group (Fig. 3 ). Among TXA-treated patients requiring revision surgery, two-thirds received daily TXA doses below 1,500 mg (500 mg: 16.7%; 750 mg: 50%). Two of six patients (33.3%) received a total daily dose of 1,500 mg. Secondary Outcomes Before matching, five deaths (3.5%) occurred in the control group within 90 days, whereas no deaths were observed in the TXA group. After matching, one death (1.4%) was recorded in the control group during the follow-up period. After matching, median preoperative hematoma volumes were comparable between groups (TXA: 104 mL; control: 94 mL; p = 0.949). No significant differences were observed in residual hematoma volume immediately postoperatively (60 mL vs. 57 mL; p = 0.637) or at one-month follow-up (20 mL vs. 25 mL; p = 0.232). Similarly, absolute hematoma volume reduction from baseline to one-month follow-up did not differ significantly between the TXA and control groups (85 mL vs. 68 mL; p = 0.361). (Fig. 4 ) Receiver operating characteristic (ROC) analysis identified postoperative residual hematoma volume as a moderate predictor of revision surgery (area under the curve [AUC] = 0.683). The optimal cutoff value was determined by maximizing the Youden index, defined as sensitivity plus specificity minus one, and was 103.5 mL. Residual hematoma volumes above this threshold were associated with an increased risk of revision surgery. In a threshold-based event analysis, the absolute proportion of clinically relevant residual hematomas (> 103.5 mL) was consistently lower in the TXA group. Postoperatively, 4/73 patients (5.5%) in the TXA group compared with 8/73 (11.0%) in the non-TXA group exceeded the cutoff (p = 0.533). At 1-month follow-up, residual hematoma volumes above the threshold were observed in 1/73 patients (1.4%) receiving TXA and 2/73 (2.7%) without TXA (p = 1.000). Discussion After propensity score matching, the study cohorts demonstrated good balance with respect to baseline characteristics. Age distribution and sex ratios were comparable between groups and consistent with those reported in similar studies [ 2 , 15 , 24 , 27 , 31 , 32 , 34 , 35 ], allowing for a valid comparative analysis both between cohorts and within the context of the current literature. Postoperative TXA administration was associated with a lower recurrence rate following surgical evacuation of chronic subdural hematoma. However, the corresponding 95% confidence interval (0.14–1.12) marginally crossed unity, indicating limited precision and statistical uncertainty. Although the point estimate favored TXA, the findings should therefore be interpreted cautiously and regarded as hypothesis-generating rather than definitive evidence of efficacy. The recurrence rate observed in the control group (19.2%) is consistent with previous reports of standard surgical treatment [ 17 , 22 ]. The magnitude and direction of the observed effect align with studies reporting reduced recurrence under TXA administration [ 15 , 27 , 31 , 34 ], while other investigations have yielded neutral or conflicting results [ 2 , 24 , 32 ]. Thus, our findings contribute to an evolving and heterogeneous body of evidence. With regard to TXA dosing, 61.6% of patients in the TXA group received a total daily dose of 1,500 mg. Notably, 66.7% of patients in the TXA group who required revision surgery had received daily doses below 1,500 mg (500 mg/day: 16.7%; 750 mg/day: 50%). Current literature does not provide a clear dose recommendation for TXA in the treatment of cSDH, with reported daily doses ranging from 500 to 1,500 mg [ 2 , 15 , 27 , 31 , 32 , 34 , 35 ]. Only the studies by Xie et al. [ 31 ] and Workewych et al. [ 32 ] administered a uniform dose of 1,500 mg/day, and among these, only Xie et al. demonstrated a significant reduction in recurrence rates. Consequently, neither the present study nor the existing literature allows for definitive conclusions regarding a dose–response relationship between TXA and recurrence reduction, underscoring the need for further investigation. Anticoagulation was explicitly included as a matching variable and was perfectly balanced in the matched cohort. A sensitivity analysis excluding all anticoagulated patients demonstrated a comparable effect estimate, although statistical significance was not retained, likely due to reduced sample size. These findings suggest that the observed association is unlikely to be solely driven by anticoagulation imbalance. Methodological limitations related to anticoagulation management, including the lack of standardized documentation regarding timing of postoperative reinitiation, are discussed in the Limitations section. No increase in mortality was observed in the TXA group. Although the retrospective nature of the study and incomplete documentation precluded systematic assessment of thromboembolic adverse events, no deaths occurred in the TXA group during the three-month follow-up period. In contrast, Salim et al. [ 24 ] reported increased mortality under TXA, attributing this finding to prothrombotic mechanisms combined with interruption of anticoagulation therapy. In our matched cohort, comorbidities and anticoagulation status were balanced, and no signal toward increased mortality was detected. In the broader context, several studies suggest that the use of TXA in neurosurgical procedures is not associated with an increased risk of thromboembolic events. This is supported by a meta-analysis by Xiong et al. [ 33 ] and a systematic review by Brown et al. [ 1 ], both of which found no significant increase in thromboembolic complications. Similarly, the TICH-2 trial reported no increase in thromboembolic events associated with TXA use in hyperacute spontaneous intracerebral hemorrhage [ 29 ]. With regard to radiological volume evolution, no significant differences in short-term hematoma volume trajectories were observed between groups. These findings are consistent with systematic reviews and meta-analyses suggesting that TXA may reduce recurrence without necessarily accelerating early volumetric resolution. In the meta-analysis by Musmar et al., TXA was associated with a significant reduction in recurrence rates and with smaller hematoma volumes during longer-term follow-up, particularly at three months, while short-term postoperative volumetric differences were less consistent [ 18 ]. Similarly, Mishra et al. reported a trend toward earlier and more complete hematoma resolution under TXA; however, these findings were insufficient to support routine TXA administration based solely on volumetric outcomes [ 14 ]. Comparable conclusions have been reported by Messias et al., who demonstrated a significant reduction in recurrence rates with TXA while observing inconsistent effects on radiological volume evolution, supporting the notion that the clinical benefit of TXA is not primarily mediated through accelerated hematoma resorption [ 12 ]. The ROC analysis suggests that recurrence risk may be threshold-dependent rather than linearly associated with residual volume. While median residual hematoma volumes did not differ between groups, there was a—albeit not statistically significant—difference in the absolute proportion of clinically relevant large residual volumes. Postoperatively, more patients in the control group exceeded the predefined threshold compared with the TXA group (8 vs. 4 cases), a pattern that persisted at the 1-month follow-up (2 vs. 1 case). The ROC analysis identified a cutoff of approximately 103.5 mL as a threshold associated with an increased risk of revision surgery. In this context, TXA does not appear to induce a global reduction in median hematoma volume but rather reduces the number of patients reaching a volume-based high-risk constellation. From a pathophysiological perspective, recurrence of cSDH is driven by persistent microhemorrhage, inflammatory activity, angiogenesis, and hyperfibrinolysis within the hematoma membranes [ 3 , 7 ]. The observed reduction in recurrence rates under TXA despite comparable volume trajectories may indicate that TXA primarily modulates these biological processes, for example by stabilizing the postoperative hematoma bed and inhibiting local fibrinolytic activity, rather than by promoting direct hematoma resorption. However, this mechanistic interpretation remains speculative and cannot be causally established based on the present data. These findings are in line with previous clinical studies, including the randomized open-label study by Wan et al. [ 31 ] and the prospective study by Yamada et al. [ 34 ], both of which reported lower recurrence rates under TXA without evidence of accelerated hematoma resorption. The role of TXA should also be considered in the context of emerging adjunctive treatment strategies. Several recent meta-analyses of randomized controlled trials have demonstrated that adjunctive or perioperative embolization of the middle meningeal artery (MMAE) is associated with a significant reduction in recurrence rates following surgical evacuation of cSDH [ 16 , 26 ]. The recurrence rates reported in these studies appear to be in a range comparable to the low revision rates observed under TXA in the present investigation. It can therefore be hypothesized that adjuvant TXA administration may reduce recurrence rates to a level that has thus far primarily been achieved through post-surgical MMAE. Should this assumption be confirmed, TXA would represent an adjuvant therapeutic option that is potentially less invasive, more widely available, and more cost-effective than endovascular embolization. However, due to differences in study design, patient populations, and endpoints, direct comparability of results is currently not justified. Such comparative evaluation requires prospective randomized studies. In this regard, the currently recruiting multicenter TABASCO trial [ 25 ] represents a promising opportunity to systematically investigate the efficacy of TXA in direct comparison with MMAE as an adjuvant treatment strategy. In summary, this matched retrospective analysis demonstrates a consistent association between postoperative TXA administration and lower recurrence rates following cSDH evacuation, despite comparable median residual hematoma volume evolution. These findings suggest that recurrence development is not solely determined by short-term volume reduction but is influenced by exceeding a critical residual volume threshold as well as underlying biological processes. However, given the width of the confidence interval and the limitations inherent to the study design, definitive conclusions regarding efficacy cannot be drawn. Whether TXA exerts its potential protective effect primarily through modulation of local hemostatic or inflammatory mechanisms, and whether it may represent a less invasive alternative to interventional adjunctive procedures, should be addressed in future prospective, ideally randomized studies. Limitations: This study has several methodological limitations. First, as a retrospective analysis, it is inherently susceptible to systematic bias, including residual confounding despite the use of propensity score matching. Although matching achieved good balance across key revision-associated covariates—such as age, hematoma architecture and baseline volume, anticoagulant use, arterial hypertension, and hematoma localization—unmeasured factors, including overall comorbidity burden or disease course, may still have differed between groups. Anticoagulation represents a well-established risk factor for recurrence. While anticoagulation status was explicitly included as a matching variable and was perfectly balanced in the matched cohort, detailed and standardized documentation regarding the timing of postoperative reinitiation of anticoagulant therapy was not consistently available. Consequently, potential differences in anticoagulation resumption strategies between groups could not be formally controlled for and may have influenced recurrence risk. In an additional sensitivity analysis excluding all patients receiving oral anticoagulation therapy, the direction and magnitude of the association between TXA and reduced recurrence remained comparable; however, statistical significance was not retained, most likely due to reduced sample size. These findings suggest that the observed association is unlikely to be solely driven by anticoagulation status, yet residual confounding related to anticoagulation management cannot be fully excluded. Second, the primary effect estimate was associated with a relatively wide 95% confidence interval that marginally crossed unity, indicating limited precision. Although the point estimate favored TXA, the study was not powered to provide definitive evidence of efficacy, and the results should therefore be interpreted with caution. Third, neither patient adherence to TXA therapy nor standardized dosing across the cohort could be ensured, substantially limiting interpretation of potential dose–response relationships. TXA administration was not governed by a predefined institutional protocol, and daily doses varied between 500 and 2,000 mg. Fourth, the overall follow-up period of three months restricts conclusions regarding long-term outcomes, including mortality and late recurrence. Radiological follow-up was limited to one month postoperatively due to incomplete imaging data beyond this time point. Although no deaths occurred in the TXA group, systematic data on thromboembolic events were unavailable, precluding formal safety assessment. Methodologically, propensity score matching is associated with loss of statistical power due to exclusion of unmatched patients, reducing effective sample size, even though complete matching was achieved for the TXA cohort. Finally, propensity score methods account only for observed covariates; unmeasured confounders influencing both treatment allocation and outcomes may persist, and residual bias cannot be excluded. Conclusion In this propensity score–matched analysis, postoperative tranexamic acid was associated with a lower rate of revision surgery following chronic subdural hematoma evacuation. However, the corresponding 95% confidence interval was wide and marginally crossed unity, indicating limited precision and statistical uncertainty. These findings should therefore not be interpreted as definitive evidence of efficacy. No increase in mortality was observed. Although overall hematoma volume reduction did not differ significantly between groups, TXA-treated patients less frequently exceeded a clinically relevant residual volume threshold. Given the retrospective design and limited statistical power, the results are hypothesis-generating and require confirmation in adequately powered prospective randomized trials. Abbreviations CI Confidence intervals CKD Chronic kidney disease cSDH Chronic subdural hematoma ml millilitre PAI Platelet aggregation inhibition presur. presurgical PSM Propensity Score Matching ROC Receiver operating characteristic TXA Tranexamic acid Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Ulm University on October 10, 2023 (approval number: 311/23) and was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. This study was conducted as a retrospective analysis of routinely collected clinical data. All data were pseudonymized prior to analysis and fully anonymized for publication. According to § 15(3) of the Baden-Württemberg State Data Protection Act (LDSG BW), specific informed consent was not required for this type of retrospective, pseudonymized data analysis. The study involved no additional procedures or interventions, and no risks to the patients were identified. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution Conceptualization/Methodology (M Scheer, Ch Schulz, V Beuchel), Data curation/Investigation (M Scheer, P Guenzerodt, H Witte) Formal analysis (H Witte, M. Scheer) Supervision (Ch. Schulz, UM Mauer), Writing -original draft (M Scheer) Writing -review & editing (M Scheer, Ch. Schulz) Data Availability Relevant data and materials are available by contacting the corresponding authors upon reasonable request. References Brown NJ, Hartke JN, Pacult M, Burkett KR, Gendreau J, Catapano JS, Lawton MT. Tranexamic Acid Demonstrates Efficacy without Increased Risk for Venous Thromboembolic Events in Cranial Neurosurgery: Systematic Review of the Evidence and Current Applications in Nontraumatic Pathologies. World Neurosurg. 2024;183:29–40. de Paula MVCT, Ribeiro BDC, Melo MM, de Freitas PVV, Pahl FH, de Oliveira MF, Rotta JM. Effect of postoperative tranexamic acid on recurrence rate and complications in chronic subdural hematomas patients: preliminary results of a randomized controlled clinical trial. Neurosurg Rev. 2023;46(1):90. Edlmann E, Giorgi-Coll S, Whitfield PC, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017;14(1):108. Feghali J, Yang W, Huang J. Updates in Chronic Subdural Hematoma: Epidemiology, Etiology, Pathogenesis, Treatment, and Outcome. World Neurosurg. 2020;141:339–45. Fujisawa H, Ito H, Kashiwagi S, Nomura S, Toyosawa M. Kallikrein-kinin system in chronic subdural haematomas: its roles in vascular permeability and regulation of fibrinolysis and coagulation. J Neurol Neurosurg Psychiatry. 1995;59(4):388–94. Habibi MA. Is It Safe to Use Tranexamic Acid for Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis. Asian J Neurosurg. 2025;20(2):219–28. Holl DC, Volovici V, Dirven CMF, Peul WC, van Kooten F, Jellema K, van der Gaag NA, Miah IP, Kho KH, den Hertog HM, Lingsma HF, Dammers R, Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future. World Neurosurg. 2018;116:402–e4112. Kim KH, Lee Y. Medical Management of Chronic Subdural Hematoma. Korean J Neurotrauma. 2023;19(3):288–97. Lim DJ, Chung YG, Park YK, Song JH, Lee HK, Lee KC, et al. Relationship between tissue plasminogen activator, plasminogen activator inhibitor and CT image in chronic subdural hematoma. J Korean Med Sci. 1995;10:373–8. Liu W, Bakker NA, Groen RJ. Chronic subdural hematoma: a systematic review and meta-analysis of surgical procedures. J Neurosurg. 2014;121(3):665–73. Mehta V, Harward SC, Sankey EW, Nayar G, Codd PJ. Evidence based diagnosis and management of chronic subdural hematoma: A review of the literature. J Clin Neurosci. 2018;50:7–15. Messias BR. Chronic Subdural Hematoma and Tranexamic Acid: A Systematic Review. Turk Neurosurg. 2025;35(4):527–36. Mikkelsen R, Anker-Møller T, Hvas AM, Sunde N. A Case of Tranexamic Acid as Adjunctive Treatment for Chronic Subdural Hematoma with Multiple Recurrences. Am J Case Rep. 2017;18:995–9. Mishra R. Role of Tranexamic Acid in the Management of Chronic Subdural Hematoma: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Neurol India. 2025;73(1):17–28. Miyakoshi A, Nakatani E, Kaneda H, Hawke P, Sasaki H, Urano T, et al. Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population. J Neurosurg. 2023;93:1160–1137. Mohammadzadeh I, Hajikarimloo B, Zare A, Mohammadzadeh S, Eini P, Aghajani S, Mortezaei A, Habibi MA, Yangi K, Günkan A, Jabbour P. Efficacy of middle meningeal artery embolization combined with surgery versus standalone surgery for chronic subdural hematoma: a comprehensive systematic review and Meta-Analysis with separate analysis of randomized controlled trials. Neuroradiology. 2025;67(10):2897–919. Motiei-Langroudi R, Stippler M, Shi S, et al. Factors predicting reoperation of chronic subdural hematoma following primary surgical evacuation. J Neurosurg. 2018;129(5):1143–50. Musmar B. Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma: a systematic review and meta-analysis. J Neurosurg. 2024;141(4):945–54. Nakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001;95(2):256–62. Ng W, Jerath A, Wąsowicz M. Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther. 2015;47(4):339–50. Nouri A, Gondar R, Schaller K, Meling T. Chronic Subdural Hematoma (cSDH): A review of the current state of the art. Brain Spine. 2021;1(100300):1–9. Ohba S, Kinoshita Y, Nakagawa T, Murakami H. The risk factors for recurrence of chronic subdural hematoma. Neurosurg Rev. 2013;36(1):145–50. Pan W, Hu J, Huang X, Jin E, Yao L, Han J, Liu T. Effectiveness of tranexamic acid on chronic subdural hematoma recurrence: a meta-analysis and systematic review. Front Neurol. 2024;15. Salim HA, Khayat N, Chen H, Balar AB, Colasurdo M, Adeeb N, Musmar B, Essibayi MA, Msherghi A, Bhatia S, Dmytriw AA, Faizy TD, Wintermark M, Yedavalli V, Malhotra A, Gandhi D, Lakhani DA. Tranexamic acid with surgery vs. surgery alone for chronic subdural hematoma: Propensity score-matched analysis. Clin Neurol Neurosurg. 2025;257:109071. Scheer M, Beuchel V, Mauer UM, Efinger K, Schulz C. Tranexamic acid vs. embolization of the meningeal artery as an adjunctive therapeutic regime to reduce the recurrence rate after surgical relief of chronic subdural hematomas (TABASCO)-a randomized controlled trial. Trials. 2025;26(1):207. Shakir M, Ali Z, Huang Y, Siddiq F. Adjunctive middle meningeal artery embolization for chronic subdural hematoma: a systematic review and meta-analysis of randomized controlled trials. Neurol Res 2025 Nov 23:1–14. Shibahashi K, Ohbe H, Yasunaga H. Adjuvant oral tranexamic acid and reoperation after burr hole surgery in patients with chronic subdural hematoma: propensity score-matched analysis using a nationwide inpatient database. J Neurosurg. 2022;138(2):430–6. Stanisic M, Lund-Johansen M, Mahesparan R. Treatment of chronic subdural hematoma by burr-hole craniostomy in adults: influence of some factors on postoperative recurrence. Acta Neurochir (Wien). 2005;147(12):1249–56. Sprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, Christensen H, Ciccone A, Collins R, Czlonkowska A, Dineen RA, Duley L, Egea-Guerrero JJ, England TJ, Krishnan K, Laska AC, Law ZK, Ozturk S, Pocock SJ, Roberts I, Robinson TG, Roffe C, Seiffge D, Scutt P, Thanabalan J, Werring D, Whynes D, Bath PM. TICH-2 Investigators. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107–15. Stary JM, Hutchins L, Vega RA. Tranexamic Acid for Recurring Subdural Hematomas Following Surgical Evacuation: A Clinical Case Series. J Neurol Surg Cent Eur Neurosurg. 2016;77(5):422–6. Wan KR, Qiu L, Saffari SE, Khong WXL, Ong JCL, See AA, Ng WH, King NKK. An open label randomized trial to assess the efficacy of tranexamic acid in reducing post-operative recurrence of chronic subdural haemorrhage. J Clin Neurosci. 2020;82(Pt A):147–54. Workewych A, Callum J, Saarela O, Montanera W, Cusimano MD. Tranexamic acid in the treatment of residual chronic subdural hematoma: a single-centre, randomized controlled trial (TRACE). J Neurotrauma. 2018;35:A244–5. Xiong Y, Guo X, Huang X, Kang X, Zhou J, Chen C, Pan Z, Wang L, Goldbrunner R, Stavrinou L, Stavrinou P, Lin S, Chen Y, Hu W, Zheng F. Efficacy and safety of tranexamic acid in intracranial haemorrhage: A meta-analysis. PLoS ONE. 2023;18(3):e0282726. Yamada T, Natori Y. Prospective study on the efficacy of orally administered tranexamic acid and Goreisan for the prevention of recurrence after chronic subdural hematoma Burr hole surgery. World Neurosurg. 2020;134:e549–53. Yang K, Kim KH, Lee HJ, Jeong EO, Kwon HJ, Choi SW, Kim SH, Koh HS, Youm JY. Role of Adjunctive. Tranexamic Acid in. Facilitating Resolution of Chronic Subdural Hematoma after Surgery. J Korean. Neurosurg Soc. 2022 Nov 3. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 May, 2026 Reviews received at journal 28 Apr, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviews received at journal 17 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers invited by journal 16 Apr, 2026 Editor assigned by journal 16 Apr, 2026 Editor invited by journal 15 Apr, 2026 Submission checks completed at journal 14 Apr, 2026 First submitted to journal 14 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9361375","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":628591412,"identity":"6d9d19c2-74f5-4d53-84e8-ca0145318c63","order_by":0,"name":"Magnus Scheer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYDADAxDxsQFIHABixgYitTDOJFkLMy8xWnTbj197zPOnTt6cvfnYZ9sdh/P4jrc/k/i44x4Dv/TxC9i0mJ3JKTfmbTtsuLPnWPLs3DOHiyXPnDGTnHmmmEGyL6cAq5YDOWnSvA0HEgxu5Bgz57YdTtxwI4ftNm9bAoPBGZ4ErFrOv0mTBjosweD++8/MliAt958/u/0Xn5Yb6cekediYgbbwMDMzgm1hMLvNCNbCfgC7ljdsknOBftlwJs2YsfdMeuLMMznmP3vbEngke3iwhpjZ+fRnEm+AIWZw/PBjhp87rBP7jh9/bPCzLUGOn4f9AVY9DDwGOMRxS+EyCr/UKBgFo2AUjCQAAAe1bfLHcClKAAAAAElFTkSuQmCC","orcid":"","institution":"Bundeswehrkrankenhaus Ulm","correspondingAuthor":true,"prefix":"","firstName":"Magnus","middleName":"","lastName":"Scheer","suffix":""},{"id":628591414,"identity":"d33874b6-a39d-4e74-aa04-4935178b7775","order_by":1,"name":"Hanno Witte","email":"","orcid":"","institution":"Bundeswehrkrankenhaus Ulm","correspondingAuthor":false,"prefix":"","firstName":"Hanno","middleName":"","lastName":"Witte","suffix":""},{"id":628591415,"identity":"0b016a16-ff01-4201-a6d9-b063822a59be","order_by":2,"name":"Paulina Guenzerodt","email":"","orcid":"","institution":"University Hospital Augsburg","correspondingAuthor":false,"prefix":"","firstName":"Paulina","middleName":"","lastName":"Guenzerodt","suffix":""},{"id":628591416,"identity":"8da59b4d-f136-42a9-b808-6efd5cfc8c80","order_by":3,"name":"Vanessa Beuchel","email":"","orcid":"","institution":"Bundeswehrkrankenhaus Westerstede","correspondingAuthor":false,"prefix":"","firstName":"Vanessa","middleName":"","lastName":"Beuchel","suffix":""},{"id":628591417,"identity":"fbdfb712-fde2-4724-864e-003e235215bb","order_by":4,"name":"Uwe Max Mauer","email":"","orcid":"","institution":"Bundeswehrkrankenhaus Ulm","correspondingAuthor":false,"prefix":"","firstName":"Uwe","middleName":"Max","lastName":"Mauer","suffix":""},{"id":628591418,"identity":"9560ed9e-faaa-4c01-952c-22b7c50629fd","order_by":5,"name":"Chris Schulz","email":"","orcid":"","institution":"Bundeswehrkrankenhaus Ulm","correspondingAuthor":false,"prefix":"","firstName":"Chris","middleName":"","lastName":"Schulz","suffix":""}],"badges":[],"createdAt":"2026-04-08 22:53:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9361375/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9361375/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107833974,"identity":"242da9cb-d9ef-4c3a-ba7b-8b2881cb5a98","added_by":"auto","created_at":"2026-04-26 15:42:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136284,"visible":true,"origin":"","legend":"\u003cp\u003eStudy design, TXA: tranexamic acid\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9361375/v1/f34e3c195cca59eeb77d0533.png"},{"id":107870413,"identity":"55f01491-8988-42bd-9bac-ceb236562da3","added_by":"auto","created_at":"2026-04-27 07:39:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":44765,"visible":true,"origin":"","legend":"\u003cp\u003eRate of revision in each group, TXA: tranexamic acid\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9361375/v1/eb24cad2f484e1cf705b0ab8.png"},{"id":107833976,"identity":"6d0d11a9-4d8d-4c7c-afd1-d36d11f68ddd","added_by":"auto","created_at":"2026-04-26 15:42:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":30198,"visible":true,"origin":"","legend":"\u003cp\u003eTime interval between initial surgery and revision in days, depending on treatment arm, TXA: tranexamic acid\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9361375/v1/1e2a2ea03b79ef711008ce11.png"},{"id":108006350,"identity":"383bcc28-828d-47b2-b006-3ec44a17faf6","added_by":"auto","created_at":"2026-04-28 12:55:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":262273,"visible":true,"origin":"","legend":"\u003cp\u003eVolume development from preoperatively to a one-month follow-up; the red line represents the median volume development per treatment arm. TXA: tranexamic acid\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-9361375/v1/c465743f6b7dc9ea3d022d04.png"},{"id":108008598,"identity":"5b3bf82e-c862-42b3-bb0a-6ffcd3237db4","added_by":"auto","created_at":"2026-04-28 13:07:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":683455,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9361375/v1/1de2105f-d677-4e54-babb-a77656b21d66.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Revision rate and postoperative volume development of chronic subdural hematomas after burr hole craniotomy in combination with tranexamic acid vs. surgery alone – a single-center propensity score- matched analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic subdural hematoma (cSDH) represents one of the most common traumatic intracranial hemorrhages in Western industrialized countries [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. It is defined as a persistent accumulation of hemorrhagic to serous fluid within the subdural space, typically resulting from a mild traumatic brain injury that occurred several weeks earlier. The reported incidence (1.7\u0026ndash;20.6 per 100,000 inhabitants) increases significantly with age, posing a growing challenge in the context of ongoing demographic change [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathophysiology of cSDH is complex and cannot be explained solely by the accumulation of blood following rupture of bridging veins. Rather, the underlying mechanism is thought to involve injury to the dural border cell layer, a highly specialized connective tissue cell layer located between the dura mater and the arachnoid mater. Disruption of this layer initiates a local inflammatory response, which, through the induction of angiogenesis, leads to the formation of pathological, thin-walled capillaries that are prone to rupture and cause recurrent microhemorrhages. In parallel, plasminogen-activated hyperfibrinolysis of the hematoma content\u0026mdash;considered an acute-phase reaction\u0026mdash;impairs physiological clot formation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This results in a self-perpetuating cycle of cellular proliferation, angiogenesis, hyperfibrinolysis, and recurrent bleeding, ultimately driving the progressive enlargement of the hematoma [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment strategies for cSDH range from conservative management in asymptomatic patients with small hematomas (wait-and-watch strategy) to surgical decompression in cases of radiologically confirmed brain compression accompanied by neurological deficits [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Surgical approaches include burr-hole trephination or craniotomy with drainage [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Regardless of the surgical technique employed, relatively high recurrence rates (2.3%\u0026ndash;38.7%) requiring revision surgery have been reported [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In light of these recurrence rates, adjunctive conservative treatment strategies have gained increasing attention [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], with particular focus on targeting hyperfibrinolysis. Several studies investigating perioperative pharmacological therapy have reported promising results with tranexamic acid (TXA) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. As a specific antifibrinolytic agent, TXA inhibits plasminogen activation and thereby suppresses hyperfibrinolysis within the hematoma, potentially preventing re-expansion of cSDH through the reduction of recurrent microbleeding [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, this therapeutic approach remains controversial, as several studies have also reported no significant reduction in recurrence rates or even increased mortality associated with adjuvant TXA therapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of the present study was to evaluate the efficacy of tranexamic acid with regard to reducing postoperative recurrence rates as well as postoperative hematoma volume reduction following surgical evacuation of chronic subdural hematomas.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and Inclusion Criteria:\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed patients treated for chronic subdural hematoma (cSDH) at the Department of Neurosurgery, German Armed Forces Hospital in Ulm, between 2012 and 2024. All patients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years who underwent unilateral or bilateral hematoma evacuation via burr-hole craniotomy with placement of a subdural drain during this period were eligible for inclusion. Patients with incomplete clinical data, including missing or incomplete cross-sectional imaging, as well as patients who developed an acute subdural hematoma due to immediate postoperative rebleeding, were excluded.\u003c/p\u003e \u003cp\u003e Two cohorts were defined: an intervention group comprising patients who received oral tranexamic acid (TXA), initiated within two days after surgical evacuation of cSDH and continued for a minimum of 30 days, without any preceding intravenous loading dose or transition regimen, and a control group consisting of patients who underwent surgical treatment without adjuvant therapy.\u003c/p\u003e \u003cp\u003eTXA was introduced at our institution in 2012 as an adjunctive option for recurrence prophylaxis based on emerging evidence in the literature. Throughout the study period, surgical and postoperative management of cSDH remained unchanged.\u003c/p\u003e \u003cp\u003eTXA use was at the discretion of the treating neurosurgeon and was not governed by a predefined institutional protocol. The only contraindications were known hypersensitivity and active thromboembolic disease. No standardized dose adjustments were applied based on renal function. Thromboelastography was not used.\u003c/p\u003e \u003cp\u003e This cohort study was approved by the Ethics Committee of Ulm University on October 10, 2023 (approval number: 311/23) and was conducted in accordance with the Declaration of Helsinki as revised in 2008.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Outcomes:\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the need for revision surgery due to recurrent hematoma within three months following the initial operation.\u003c/p\u003e \u003cp\u003eSecondary outcomes included postoperative volume evolution of the residual hematoma in the immediate postoperative period and at one-month follow-up, as well as overall mortality in both groups during a total observation period of three months.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis:\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) with the packages \u003cem\u003eMatchIt, tableone, pROC, effsize, dplyr, tidyr\u003c/em\u003e and \u003cem\u003eggplot2\u003c/em\u003e. To account for baseline imbalances between patients treated with tranexamic acid (TXA) and those without TXA, we applied propensity score matching using the \u003cem\u003eMatchIt\u003c/em\u003e package. The propensity score was estimated in a logistic regression model with TXA exposure as the dependent variable and age, hematoma architecture classified according to the Nakaguchi classification [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and pre-existing anticoagulation as covariates. Patients were then matched in a 1:1 ratio using optimal matching based on the logit of the propensity score. Covariate balance before and after matching was assessed with the \u003cem\u003etableone\u003c/em\u003e package by comparing summary statistics and calculating standardized mean differences for all baseline variables. Group comparisons between TXA and no-TXA patients in the matched cohort were performed using \u003cem\u003eCreateTableOne\u003c/em\u003e, which employs χ\u0026sup2; tests or Fisher\u0026rsquo;s exact tests for categorical variables and Student\u0026rsquo;s t tests or Wilcoxon rank-sum tests for continuous variables, as appropriate.\u003c/p\u003e \u003cp\u003eThe primary outcome was the need for surgical revision. The association between TXA use and revision surgery was evaluated in the matched sample using contingency tables and Fisher\u0026rsquo;s exact test. Additionally, a sensitivity analysis was performed after exclusion of all patients receiving oral anticoagulation therapy to assess the robustness of the primary findings. Recurrence rates were compared using Fisher\u0026rsquo;s exact test, and odds ratios with 95% confidence intervals were calculated. This analysis was exploratory and not powered for subgroup comparisons. To determine an optimal hematoma volume threshold for predicting revision, receiver operating characteristic (ROC) analysis was conducted with the \u003cem\u003epROC\u003c/em\u003e package, using revision (yes/no) as the binary outcome and preoperative hematoma volume as the continuous predictor. The optimal cut-off was derived from the Youden index. To quantify patients with a hematoma volume exceeding the ROC-based cut-off, a dichotomous event variable was created. Group comparisons were performed using a two-sided Fisher\u0026rsquo;s exact test due to low event rates. Changes in hematoma volume over time (VolDiff: preoperative to postoperative change; VolDiff2: postoperative to 1-month follow-up change) were summarized by means and standard deviations within each group and compared between TXA and no-TXA patients using both Student\u0026rsquo;s t tests and Wilcoxon rank-sum tests. Effect sizes for volume reduction were quantified using Cohen\u0026rsquo;s d with the \u003cem\u003eeffsize\u003c/em\u003e package. Unless stated otherwise, all tests were two-sided and a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics:\u003c/h2\u003e \u003cp\u003eBetween January 2012 and October 2024, a total of 236 patients with chronic subdural hematoma (cSDH) were treated by burr-hole trephination with placement of a subdural drain at the Department of Neurosurgery, Bundeswehr Hospital Ulm. Of these, 216 patients met the inclusion criteria for the retrospective cohort analysis. Within the study population, 73 patients received adjuvant oral therapy with tranexamic acid (TXA), initiated within 48 hours after surgery and continued for a minimum of 30 days. The remaining 143 patients underwent standard treatment consisting of surgical hematoma evacuation without additional therapy. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn the unmatched cohort, significant differences between groups were observed, particularly with respect to the use of direct oral anticoagulants (DOACs) (35 vs. 3 patients, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After propensity score matching, 73 patients remained in each group, with adequate balance of the selected covariates. Specifically, the use of DOACs (3 vs. 3, p\u0026thinsp;=\u0026thinsp;1.000), Nakaguchi classification (type I: 38 vs. 38; type II: 7 vs. 5; type III: 4 vs. 4; type IV: 24 vs. 26; p\u0026thinsp;=\u0026thinsp;0.937), history of hypertension (34 vs. 34, p\u0026thinsp;=\u0026thinsp;1.000), and use of platelet aggregation inhibitors (13 vs. 13, p\u0026thinsp;=\u0026thinsp;1.000) were evenly distributed between the groups. No statistically significant differences in baseline characteristics were observed after matching.\u003c/p\u003e \u003cp\u003eFollowing propensity score matching, age and sex distributions were comparable between the TXA and control groups. In the TXA group, 50 patients were male (68.5%) and 23 were female (31.5%), whereas in the non-TXA group, 59 patients were male (80.8%) and 14 were female (19.2%); the difference in sex distribution was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.128). Mean age was 72.90 years in the TXA group and 73.29 years in the control group (p\u0026thinsp;=\u0026thinsp;0.855), indicating successful balancing of these baseline characteristics through matching. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn the TXA group, the mean daily dose of tranexamic acid was 1,226 mg administered for a minimum duration of 30 days (range: 500\u0026ndash;2,000 mg). Forty-five patients (61.6%) received a total daily dose of 1,500 mg, divided into two or three administrations. Fourteen patients (19.2%) received 500 mg, four patients (5.5%) received 750 mg, eight patients (11.0%) received 1,000 mg, and two patients (2.7%) received 2,000 mg as the total daily dose.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics and results pre- and post-matching, CKD, chronic kidney disease; PAI, platelet aggregation inhibition, TXA, tranexamic acid, Preop, preoperativ\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMatched pairs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo TXA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;143)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTXA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo TXA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTXA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eSex: n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112(78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (68.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59 (80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50 (68.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (31.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (31.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (median)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.855\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNakaguchi Score: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (6.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (5.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26 (35.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCKD: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32 (48.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnticoagulation: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePAI: n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (30.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSeizure: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocalization: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.790\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (42.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (38.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHematoma volume: ml (median)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epreoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.949\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epostoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.881\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 month postoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDecrease\u003c/em\u003e preop to\u003c/p\u003e \u003cp\u003e1 month postsurgical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRevision: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplications: n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.0175**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurologic impairment*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery related\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e* new after surgery ** overall complications\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures:\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003ePrimary Outcome\u003c/h2\u003e \u003cp\u003eBefore propensity score matching, the 90-day revision surgery rate was higher in the control group than in the TXA group (16.1% vs. 8.2%; OR\u0026thinsp;=\u0026thinsp;0.452; 95% CI: 0.175\u0026ndash;1.65), without reaching statistical significance (p\u0026thinsp;=\u0026thinsp;0.178). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) After matching, the revision rate was higher in the control group compared with the TXA group (19.2% vs. 8.2%; OR\u0026thinsp;=\u0026thinsp;0.400; 95% CI: 0.143\u0026ndash;1.118; p\u0026thinsp;=\u0026thinsp;0.042). In the analysis after exclusion of all patients receiving oral anticoagulation therapy, recurrence occurred in 7.1% of TXA-treated patients and in 19.4% of controls (OR 0.37; 95% CI 0.10\u0026ndash;1.12; p\u0026thinsp;=\u0026thinsp;0.068). Median time to revision surgery was 11 days (range: 1\u0026ndash;91 days) in the control group and 8 days (range: 8\u0026ndash;14 days) in the TXA group (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Among TXA-treated patients requiring revision surgery, two-thirds received daily TXA doses below 1,500 mg (500 mg: 16.7%; 750 mg: 50%). Two of six patients (33.3%) received a total daily dose of 1,500 mg.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eSecondary Outcomes\u003c/h3\u003e\n\u003cp\u003eBefore matching, five deaths (3.5%) occurred in the control group within 90 days, whereas no deaths were observed in the TXA group. After matching, one death (1.4%) was recorded in the control group during the follow-up period.\u003c/p\u003e \u003cp\u003eAfter matching, median preoperative hematoma volumes were comparable between groups (TXA: 104 mL; control: 94 mL; p\u0026thinsp;=\u0026thinsp;0.949). No significant differences were observed in residual hematoma volume immediately postoperatively (60 mL vs. 57 mL; p\u0026thinsp;=\u0026thinsp;0.637) or at one-month follow-up (20 mL vs. 25 mL; p\u0026thinsp;=\u0026thinsp;0.232).\u003c/p\u003e \u003cp\u003eSimilarly, absolute hematoma volume reduction from baseline to one-month follow-up did not differ significantly between the TXA and control groups (85 mL vs. 68 mL; p\u0026thinsp;=\u0026thinsp;0.361). (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eReceiver operating characteristic (ROC) analysis identified postoperative residual hematoma volume as a moderate predictor of revision surgery (area under the curve [AUC]\u0026thinsp;=\u0026thinsp;0.683). The optimal cutoff value was determined by maximizing the Youden index, defined as sensitivity plus specificity minus one, and was \u003cem\u003e103.5 mL.\u003c/em\u003e Residual hematoma volumes above this threshold were associated with an increased risk of revision surgery. In a threshold-based event analysis, the absolute proportion of clinically relevant residual hematomas (\u0026gt;\u0026thinsp;103.5 mL) was consistently lower in the TXA group. Postoperatively, 4/73 patients (5.5%) in the TXA group compared with 8/73 (11.0%) in the non-TXA group exceeded the cutoff (p\u0026thinsp;=\u0026thinsp;0.533). At 1-month follow-up, residual hematoma volumes above the threshold were observed in 1/73 patients (1.4%) receiving TXA and 2/73 (2.7%) without TXA (p\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAfter propensity score matching, the study cohorts demonstrated good balance with respect to baseline characteristics. Age distribution and sex ratios were comparable between groups and consistent with those reported in similar studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], allowing for a valid comparative analysis both between cohorts and within the context of the current literature.\u003c/p\u003e \u003cp\u003ePostoperative TXA administration was associated with a lower recurrence rate following surgical evacuation of chronic subdural hematoma. However, the corresponding 95% confidence interval (0.14\u0026ndash;1.12) marginally crossed unity, indicating limited precision and statistical uncertainty. Although the point estimate favored TXA, the findings should therefore be interpreted cautiously and regarded as hypothesis-generating rather than definitive evidence of efficacy. The recurrence rate observed in the control group (19.2%) is consistent with previous reports of standard surgical treatment [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The magnitude and direction of the observed effect align with studies reporting reduced recurrence under TXA administration [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], while other investigations have yielded neutral or conflicting results [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Thus, our findings contribute to an evolving and heterogeneous body of evidence.\u003c/p\u003e \u003cp\u003eWith regard to TXA dosing, 61.6% of patients in the TXA group received a total daily dose of 1,500 mg. Notably, 66.7% of patients in the TXA group who required revision surgery had received daily doses below 1,500 mg (500 mg/day: 16.7%; 750 mg/day: 50%). Current literature does not provide a clear dose recommendation for TXA in the treatment of cSDH, with reported daily doses ranging from 500 to 1,500 mg [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Only the studies by Xie et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and Workewych et al. [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] administered a uniform dose of 1,500 mg/day, and among these, only Xie et al. demonstrated a significant reduction in recurrence rates. Consequently, neither the present study nor the existing literature allows for definitive conclusions regarding a dose\u0026ndash;response relationship between TXA and recurrence reduction, underscoring the need for further investigation.\u003c/p\u003e \u003cp\u003eAnticoagulation was explicitly included as a matching variable and was perfectly balanced in the matched cohort. A sensitivity analysis excluding all anticoagulated patients demonstrated a comparable effect estimate, although statistical significance was not retained, likely due to reduced sample size. These findings suggest that the observed association is unlikely to be solely driven by anticoagulation imbalance. Methodological limitations related to anticoagulation management, including the lack of standardized documentation regarding timing of postoperative reinitiation, are discussed in the Limitations section.\u003c/p\u003e \u003cp\u003eNo increase in mortality was observed in the TXA group. Although the retrospective nature of the study and incomplete documentation precluded systematic assessment of thromboembolic adverse events, no deaths occurred in the TXA group during the three-month follow-up period. In contrast, Salim et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] reported increased mortality under TXA, attributing this finding to prothrombotic mechanisms combined with interruption of anticoagulation therapy. In our matched cohort, comorbidities and anticoagulation status were balanced, and no signal toward increased mortality was detected. In the broader context, several studies suggest that the use of TXA in neurosurgical procedures is not associated with an increased risk of thromboembolic events. This is supported by a meta-analysis by Xiong et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and a systematic review by Brown et al. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], both of which found no significant increase in thromboembolic complications. Similarly, the TICH-2 trial reported no increase in thromboembolic events associated with TXA use in hyperacute spontaneous intracerebral hemorrhage [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWith regard to radiological volume evolution, no significant differences in short-term hematoma volume trajectories were observed between groups. These findings are consistent with systematic reviews and meta-analyses suggesting that TXA may reduce recurrence without necessarily accelerating early volumetric resolution. In the meta-analysis by Musmar et al., TXA was associated with a significant reduction in recurrence rates and with smaller hematoma volumes during longer-term follow-up, particularly at three months, while short-term postoperative volumetric differences were less consistent [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Similarly, Mishra et al. reported a trend toward earlier and more complete hematoma resolution under TXA; however, these findings were insufficient to support routine TXA administration based solely on volumetric outcomes [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Comparable conclusions have been reported by Messias et al., who demonstrated a significant reduction in recurrence rates with TXA while observing inconsistent effects on radiological volume evolution, supporting the notion that the clinical benefit of TXA is not primarily mediated through accelerated hematoma resorption [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ROC analysis suggests that recurrence risk may be threshold-dependent rather than linearly associated with residual volume. While median residual hematoma volumes did not differ between groups, there was a\u0026mdash;albeit not statistically significant\u0026mdash;difference in the absolute proportion of clinically relevant large residual volumes. Postoperatively, more patients in the control group exceeded the predefined threshold compared with the TXA group (8 vs. 4 cases), a pattern that persisted at the 1-month follow-up (2 vs. 1 case). The ROC analysis identified a cutoff of approximately 103.5 mL as a threshold associated with an increased risk of revision surgery. In this context, TXA does not appear to induce a global reduction in median hematoma volume but rather reduces the number of patients reaching a volume-based high-risk constellation.\u003c/p\u003e \u003cp\u003eFrom a pathophysiological perspective, recurrence of cSDH is driven by persistent microhemorrhage, inflammatory activity, angiogenesis, and hyperfibrinolysis within the hematoma membranes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The observed reduction in recurrence rates under TXA despite comparable volume trajectories may indicate that TXA primarily modulates these biological processes, for example by stabilizing the postoperative hematoma bed and inhibiting local fibrinolytic activity, rather than by promoting direct hematoma resorption. However, this mechanistic interpretation remains speculative and cannot be causally established based on the present data. These findings are in line with previous clinical studies, including the randomized open-label study by Wan et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and the prospective study by Yamada et al. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], both of which reported lower recurrence rates under TXA without evidence of accelerated hematoma resorption.\u003c/p\u003e \u003cp\u003eThe role of TXA should also be considered in the context of emerging adjunctive treatment strategies. Several recent meta-analyses of randomized controlled trials have demonstrated that adjunctive or perioperative embolization of the middle meningeal artery (MMAE) is associated with a significant reduction in recurrence rates following surgical evacuation of cSDH [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The recurrence rates reported in these studies appear to be in a range comparable to the low revision rates observed under TXA in the present investigation. It can therefore be hypothesized that adjuvant TXA administration may reduce recurrence rates to a level that has thus far primarily been achieved through post-surgical MMAE. Should this assumption be confirmed, TXA would represent an adjuvant therapeutic option that is potentially less invasive, more widely available, and more cost-effective than endovascular embolization. However, due to differences in study design, patient populations, and endpoints, direct comparability of results is currently not justified. Such comparative evaluation requires prospective randomized studies. In this regard, the currently recruiting multicenter TABASCO trial [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] represents a promising opportunity to systematically investigate the efficacy of TXA in direct comparison with MMAE as an adjuvant treatment strategy.\u003c/p\u003e \u003cp\u003eIn summary, this matched retrospective analysis demonstrates a consistent association between postoperative TXA administration and lower recurrence rates following cSDH evacuation, despite comparable median residual hematoma volume evolution. These findings suggest that recurrence development is not solely determined by short-term volume reduction but is influenced by exceeding a critical residual volume threshold as well as underlying biological processes. However, given the width of the confidence interval and the limitations inherent to the study design, definitive conclusions regarding efficacy cannot be drawn. Whether TXA exerts its potential protective effect primarily through modulation of local hemostatic or inflammatory mechanisms, and whether it may represent a less invasive alternative to interventional adjunctive procedures, should be addressed in future prospective, ideally randomized studies.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations:\u003c/h2\u003e \u003cp\u003eThis study has several methodological limitations. First, as a retrospective analysis, it is inherently susceptible to systematic bias, including residual confounding despite the use of propensity score matching. Although matching achieved good balance across key revision-associated covariates\u0026mdash;such as age, hematoma architecture and baseline volume, anticoagulant use, arterial hypertension, and hematoma localization\u0026mdash;unmeasured factors, including overall comorbidity burden or disease course, may still have differed between groups.\u003c/p\u003e \u003cp\u003eAnticoagulation represents a well-established risk factor for recurrence. While anticoagulation status was explicitly included as a matching variable and was perfectly balanced in the matched cohort, detailed and standardized documentation regarding the timing of postoperative reinitiation of anticoagulant therapy was not consistently available. Consequently, potential differences in anticoagulation resumption strategies between groups could not be formally controlled for and may have influenced recurrence risk. In an additional sensitivity analysis excluding all patients receiving oral anticoagulation therapy, the direction and magnitude of the association between TXA and reduced recurrence remained comparable; however, statistical significance was not retained, most likely due to reduced sample size. These findings suggest that the observed association is unlikely to be solely driven by anticoagulation status, yet residual confounding related to anticoagulation management cannot be fully excluded.\u003c/p\u003e \u003cp\u003eSecond, the primary effect estimate was associated with a relatively wide 95% confidence interval that marginally crossed unity, indicating limited precision. Although the point estimate favored TXA, the study was not powered to provide definitive evidence of efficacy, and the results should therefore be interpreted with caution.\u003c/p\u003e \u003cp\u003eThird, neither patient adherence to TXA therapy nor standardized dosing across the cohort could be ensured, substantially limiting interpretation of potential dose\u0026ndash;response relationships. TXA administration was not governed by a predefined institutional protocol, and daily doses varied between 500 and 2,000 mg.\u003c/p\u003e \u003cp\u003eFourth, the overall follow-up period of three months restricts conclusions regarding long-term outcomes, including mortality and late recurrence. Radiological follow-up was limited to one month postoperatively due to incomplete imaging data beyond this time point. Although no deaths occurred in the TXA group, systematic data on thromboembolic events were unavailable, precluding formal safety assessment.\u003c/p\u003e \u003cp\u003eMethodologically, propensity score matching is associated with loss of statistical power due to exclusion of unmatched patients, reducing effective sample size, even though complete matching was achieved for the TXA cohort. Finally, propensity score methods account only for observed covariates; unmeasured confounders influencing both treatment allocation and outcomes may persist, and residual bias cannot be excluded.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this propensity score\u0026ndash;matched analysis, postoperative tranexamic acid was associated with a lower rate of revision surgery following chronic subdural hematoma evacuation. However, the corresponding 95% confidence interval was wide and marginally crossed unity, indicating limited precision and statistical uncertainty. These findings should therefore not be interpreted as definitive evidence of efficacy. No increase in mortality was observed. Although overall hematoma volume reduction did not differ significantly between groups, TXA-treated patients less frequently exceeded a clinically relevant residual volume threshold. Given the retrospective design and limited statistical power, the results are hypothesis-generating and require confirmation in adequately powered prospective randomized trials.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCI Confidence intervals\u003c/p\u003e\u003cp\u003eCKD Chronic kidney disease\u003c/p\u003e\u003cp\u003ecSDH Chronic subdural hematoma\u003c/p\u003e\u003cp\u003eml millilitre\u003c/p\u003e\u003cp\u003ePAI Platelet aggregation inhibition\u003c/p\u003e\u003cp\u003epresur. presurgical\u003c/p\u003e\u003cp\u003ePSM Propensity Score Matching\u003c/p\u003e\u003cp\u003eROC Receiver operating characteristic\u003c/p\u003e\u003cp\u003eTXA Tranexamic acid\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003c/p\u003e\u003cp\u003e This study was approved by the Ethics Committee of Ulm University on October 10, 2023 (approval number: 311/23) and was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. This study was conducted as a retrospective analysis of routinely collected clinical data. All data were pseudonymized prior to analysis and fully anonymized for publication. According to §\u0026nbsp;15(3) of the Baden-Württemberg State Data Protection Act (LDSG BW), specific informed consent was not required for this type of retrospective, pseudonymized data analysis. The study involved no additional procedures or interventions, and no risks to the patients were identified.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003c/p\u003e\u003cp\u003eNot applicable.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization/Methodology (M Scheer, Ch Schulz, V Beuchel), Data curation/Investigation (M Scheer, P Guenzerodt, H Witte) Formal analysis (H Witte, M. Scheer) Supervision (Ch. Schulz, UM Mauer), Writing -original draft (M Scheer) Writing -review \u0026amp; editing (M Scheer, Ch. Schulz)\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eRelevant data and materials are available by contacting the corresponding authors upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBrown NJ, Hartke JN, Pacult M, Burkett KR, Gendreau J, Catapano JS, Lawton MT. Tranexamic Acid Demonstrates Efficacy without Increased Risk for Venous Thromboembolic Events in Cranial Neurosurgery: Systematic Review of the Evidence and Current Applications in Nontraumatic Pathologies. World Neurosurg. 2024;183:29\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003ede Paula MVCT, Ribeiro BDC, Melo MM, de Freitas PVV, Pahl FH, de Oliveira MF, Rotta JM. Effect of postoperative tranexamic acid on recurrence rate and complications in chronic subdural hematomas patients: preliminary results of a randomized controlled clinical trial. Neurosurg Rev. 2023;46(1):90.\u003c/li\u003e\n\u003cli\u003eEdlmann E, Giorgi-Coll S, Whitfield PC, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017;14(1):108.\u003c/li\u003e\n\u003cli\u003eFeghali J, Yang W, Huang J. Updates in Chronic Subdural Hematoma: Epidemiology, Etiology, Pathogenesis, Treatment, and Outcome. World Neurosurg. 2020;141:339\u0026ndash;45.\u003c/li\u003e\n\u003cli\u003eFujisawa H, Ito H, Kashiwagi S, Nomura S, Toyosawa M. Kallikrein-kinin system in chronic subdural haematomas: its roles in vascular permeability and regulation of fibrinolysis and coagulation. J Neurol Neurosurg Psychiatry. 1995;59(4):388\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eHabibi MA. Is It Safe to Use Tranexamic Acid for Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis. Asian J Neurosurg. 2025;20(2):219\u0026ndash;28.\u003c/li\u003e\n\u003cli\u003eHoll DC, Volovici V, Dirven CMF, Peul WC, van Kooten F, Jellema K, van der Gaag NA, Miah IP, Kho KH, den Hertog HM, Lingsma HF, Dammers R, Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future. World Neurosurg. 2018;116:402\u0026ndash;e4112.\u003c/li\u003e\n\u003cli\u003eKim KH, Lee Y. Medical Management of Chronic Subdural Hematoma. Korean J Neurotrauma. 2023;19(3):288\u0026ndash;97.\u003c/li\u003e\n\u003cli\u003eLim DJ, Chung YG, Park YK, Song JH, Lee HK, Lee KC, et al. Relationship between tissue plasminogen activator, plasminogen activator inhibitor and CT image in chronic subdural hematoma. J Korean Med Sci. 1995;10:373\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eLiu W, Bakker NA, Groen RJ. Chronic subdural hematoma: a systematic review and meta-analysis of surgical procedures. J Neurosurg. 2014;121(3):665\u0026ndash;73.\u003c/li\u003e\n\u003cli\u003eMehta V, Harward SC, Sankey EW, Nayar G, Codd PJ. Evidence based diagnosis and management of chronic subdural hematoma: A review of the literature. J Clin Neurosci. 2018;50:7\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eMessias BR. Chronic Subdural Hematoma and Tranexamic Acid: A Systematic Review. Turk Neurosurg. 2025;35(4):527\u0026ndash;36.\u003c/li\u003e\n\u003cli\u003eMikkelsen R, Anker-M\u0026oslash;ller T, Hvas AM, Sunde N. A Case of Tranexamic Acid as Adjunctive Treatment for Chronic Subdural Hematoma with Multiple Recurrences. Am J Case Rep. 2017;18:995\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eMishra R. Role of Tranexamic Acid in the Management of Chronic Subdural Hematoma: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Neurol India. 2025;73(1):17\u0026ndash;28.\u003c/li\u003e\n\u003cli\u003eMiyakoshi A, Nakatani E, Kaneda H, Hawke P, Sasaki H, Urano T, et al. Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population. J Neurosurg. 2023;93:1160\u0026ndash;1137.\u003c/li\u003e\n\u003cli\u003eMohammadzadeh I, Hajikarimloo B, Zare A, Mohammadzadeh S, Eini P, Aghajani S, Mortezaei A, Habibi MA, Yangi K, G\u0026uuml;nkan A, Jabbour P. Efficacy of middle meningeal artery embolization combined with surgery versus standalone surgery for chronic subdural hematoma: a comprehensive systematic review and Meta-Analysis with separate analysis of randomized controlled trials. Neuroradiology. 2025;67(10):2897\u0026ndash;919.\u003c/li\u003e\n\u003cli\u003eMotiei-Langroudi R, Stippler M, Shi S, et al. Factors predicting reoperation of chronic subdural hematoma following primary surgical evacuation. J Neurosurg. 2018;129(5):1143\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eMusmar B. Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma: a systematic review and meta-analysis. J Neurosurg. 2024;141(4):945\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eNakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001;95(2):256\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eNg W, Jerath A, Wąsowicz M. Tranexamic acid: a clinical review. Anaesthesiol Intensive Ther. 2015;47(4):339\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eNouri A, Gondar R, Schaller K, Meling T. Chronic Subdural Hematoma (cSDH): A review of the current state of the art. Brain Spine. 2021;1(100300):1\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eOhba S, Kinoshita Y, Nakagawa T, Murakami H. The risk factors for recurrence of chronic subdural hematoma. Neurosurg Rev. 2013;36(1):145\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003ePan W, Hu J, Huang X, Jin E, Yao L, Han J, Liu T. Effectiveness of tranexamic acid on chronic subdural hematoma recurrence: a meta-analysis and systematic review. Front Neurol. 2024;15.\u003c/li\u003e\n\u003cli\u003eSalim HA, Khayat N, Chen H, Balar AB, Colasurdo M, Adeeb N, Musmar B, Essibayi MA, Msherghi A, Bhatia S, Dmytriw AA, Faizy TD, Wintermark M, Yedavalli V, Malhotra A, Gandhi D, Lakhani DA. Tranexamic acid with surgery vs. surgery alone for chronic subdural hematoma: Propensity score-matched analysis. Clin Neurol Neurosurg. 2025;257:109071.\u003c/li\u003e\n\u003cli\u003eScheer M, Beuchel V, Mauer UM, Efinger K, Schulz C. Tranexamic acid vs. embolization of the meningeal artery as an adjunctive therapeutic regime to reduce the recurrence rate after surgical relief of chronic subdural hematomas (TABASCO)-a randomized controlled trial. Trials. 2025;26(1):207.\u003c/li\u003e\n\u003cli\u003eShakir M, Ali Z, Huang Y, Siddiq F. Adjunctive middle meningeal artery embolization for chronic subdural hematoma: a systematic review and meta-analysis of randomized controlled trials. Neurol Res 2025 Nov 23:1\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eShibahashi K, Ohbe H, Yasunaga H. Adjuvant oral tranexamic acid and reoperation after burr hole surgery in patients with chronic subdural hematoma: propensity score-matched analysis using a nationwide inpatient database. J Neurosurg. 2022;138(2):430\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eStanisic M, Lund-Johansen M, Mahesparan R. Treatment of chronic subdural hematoma by burr-hole craniostomy in adults: influence of some factors on postoperative recurrence. Acta Neurochir (Wien). 2005;147(12):1249\u0026ndash;56.\u003c/li\u003e\n\u003cli\u003eSprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, Christensen H, Ciccone A, Collins R, Czlonkowska A, Dineen RA, Duley L, Egea-Guerrero JJ, England TJ, Krishnan K, Laska AC, Law ZK, Ozturk S, Pocock SJ, Roberts I, Robinson TG, Roffe C, Seiffge D, Scutt P, Thanabalan J, Werring D, Whynes D, Bath PM. TICH-2 Investigators. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eStary JM, Hutchins L, Vega RA. Tranexamic Acid for Recurring Subdural Hematomas Following Surgical Evacuation: A Clinical Case Series. J Neurol Surg Cent Eur Neurosurg. 2016;77(5):422\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eWan KR, Qiu L, Saffari SE, Khong WXL, Ong JCL, See AA, Ng WH, King NKK. An open label randomized trial to assess the efficacy of tranexamic acid in reducing post-operative recurrence of chronic subdural haemorrhage. J Clin Neurosci. 2020;82(Pt A):147\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eWorkewych A, Callum J, Saarela O, Montanera W, Cusimano MD. Tranexamic acid in the treatment of residual chronic subdural hematoma: a single-centre, randomized controlled trial (TRACE). J Neurotrauma. 2018;35:A244\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eXiong Y, Guo X, Huang X, Kang X, Zhou J, Chen C, Pan Z, Wang L, Goldbrunner R, Stavrinou L, Stavrinou P, Lin S, Chen Y, Hu W, Zheng F. Efficacy and safety of tranexamic acid in intracranial haemorrhage: A meta-analysis. PLoS ONE. 2023;18(3):e0282726.\u003c/li\u003e\n\u003cli\u003eYamada T, Natori Y. Prospective study on the efficacy of orally administered tranexamic acid and Goreisan for the prevention of recurrence after chronic subdural hematoma Burr hole surgery. World Neurosurg. 2020;134:e549\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eYang K, Kim KH, Lee HJ, Jeong EO, Kwon HJ, Choi SW, Kim SH, Koh HS, Youm JY. Role of Adjunctive. Tranexamic Acid in. Facilitating Resolution of Chronic Subdural Hematoma after Surgery. J Korean. Neurosurg Soc. 2022 Nov 3.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Tranexamic acid, Chronic Subdural hematoma, Recurrence after surgery, Propensity score matching","lastPublishedDoi":"10.21203/rs.3.rs-9361375/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9361375/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eChronic subdural hematoma (cSDH) is a common intracranial hemorrhage in elderly patients and is associated with substantial postoperative recurrence rates. Tranexamic acid (TXA) has been proposed as an adjuvant therapy to reduce recurrence by targeting hyperfibrinolysis; however, its efficacy and impact on hematoma volume evolution remain controversial.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe performed a retrospective cohort study of adult patients who underwent burr-hole evacuation with subdural drainage for cSDH at a single neurosurgical center between 2012 and 2024. Patients receiving postoperative TXA within 48 hours for at least 30 days were compared with patients treated surgically without TXA. Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was revision surgery for recurrent cSDH within 3 months. Secondary outcomes included postoperative hematoma volume evolution and all-cause mortality.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAfter matching, 73 patients were included in each group with well-balanced baseline characteristics. Revision surgery within 90 days occurred less frequently in the TXA group compared with controls (8.2% vs. 19.2%; OR 0.40, 95% CI 0.14\u0026ndash;1.12; p\u0026thinsp;=\u0026thinsp;0.042), although the confidence interval marginally crossed unity, indicating limited precision. Median time to revision was 8 days in the TXA group and 11 days in the control group. Mortality was numerically lower in the TXA group, with no deaths observed, compared with one death (1.4%) in the control group. Preoperative, postoperative, and one-month follow-up hematoma volumes were comparable between groups, and no significant difference in absolute volume reduction was detected.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePostoperative adjuvant TXA therapy after surgical evacuation of cSDH was associated with a lower rate of recurrence requiring revision surgery, without an observed increase in mortality; however, the confidence interval marginally crossed unity, and the findings should be regarded as hypothesis-generating. TXA did not significantly influence short-term hematoma volume reduction. Prospective randomized studies are needed to confirm these findings and define optimal dosing strategies.\u003c/p\u003e","manuscriptTitle":"Revision rate and postoperative volume development of chronic subdural hematomas after burr hole craniotomy in combination with tranexamic acid vs. surgery alone – a single-center propensity score- matched analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-26 15:42:09","doi":"10.21203/rs.3.rs-9361375/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-06T03:42:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T10:23:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306237653254747588416689168133692041028","date":"2026-04-28T02:22:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-17T05:40:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3613577225130590782329156285213016160","date":"2026-04-17T05:34:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-16T14:35:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-16T14:26:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-15T06:35:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-14T17:28:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-04-14T17:11:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ee08788-d4f8-4f86-8f95-50e05e7a4b23","owner":[],"postedDate":"April 26th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-06T03:42:11+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T07:16:08+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-26 15:42:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9361375","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9361375","identity":"rs-9361375","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}