Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions encountered in the elderly population and is characterized by a gradually expanding collection of blood and fluid within the subdural space. The incidence of CSDH ranges from 1.7 to 20.6 per 100,000 persons per year and is steadily increasing due to population aging and widespread use of antiplatelet and anticoagulant medications ^[1,2]. Although minor head trauma is frequently implicated, spontaneous cases and those associated with coagulopathy are not uncommon. Pathophysiologically, CSDH is no longer considered a simple static hematoma; rather, it represents a dynamic inflammatory and angiogenic process involving fragile neomembrane formation, hyperfibrinolysis, and recurrent microhemorrhages within the hematoma cavity ^[3].

The standard treatment for symptomatic CSDH remains surgical evacuation, typically via burr-hole craniostomy or twist-drill drainage. While initial clinical outcomes are generally favorable, recurrence rates remain substantial, ranging between 5% and 30%, with some series reporting rates as high as 37% ^[4]. Recurrence often necessitates repeat surgical intervention, increasing patient morbidity, hospital stay, and healthcare costs. The risk is particularly significant in elderly patients with multiple comorbidities. Consequently, considerable attention has shifted toward adjunctive medical therapies aimed at reducing recurrence and minimizing the need for re-surgical procedures.

Tranexamic acid (TXA), a synthetic antifibrinolytic agent, competitively inhibits the activation of plasminogen to plasmin and thereby stabilizes fibrin clots. By reducing local fibrinolytic activity within the subdural hematoma cavity, TXA may interrupt the cycle of repeated microbleeding and hematoma expansion ^[5]. Emerging evidence suggests that adjunctive TXA therapy may promote faster hematoma resolution, reduce recurrence rates, and potentially decrease the need for repeat surgery. Observational studies and pilot randomized trials have demonstrated reductions in hematoma volume and favorable radiological outcomes, though results regarding recurrence and functional outcomes remain variable ^[6].

Aim

To evaluate the impact of adjunctive oral tranexamic acid on recurrence rates and the need for re-surgical intervention in patients with chronic subdural hematoma.

Objectives

1. To compare recurrence rates of chronic subdural hematoma between patients receiving adjunctive oral tranexamic acid and those managed conservatively without TXA.
2. To assess the need for re-surgical intervention in both study groups during the follow-up period.
3. To evaluate radiological and neurological outcomes at 4 and 8 weeks in patients treated with adjunctive oral TXA.

Source of Data

Data were collected prospectively from patients admitted to the Department of Neurosurgery, Government Medical College, Thiruvananthapuram. All eligible patients diagnosed with asymptomatic or minimally symptomatic primary, recurrent, or residual chronic subdural hematoma during the study period were included.

Study Design

This was a prospective cohort study.

Study Location

This prospective cohort study was conducted in the Department of Neurosurgery, Government Medical College, Thiruvananthapuram. All patients with asymptomatic or minimally symptomatic primary, recurrent, or residual CSDH admitted.

Study Duration

The study was conducted over a period of approximately four months, from January 18, 2023, to May 13, 2023. Patients were followed up at 4 weeks and 8 weeks post-enrollment.

Sample Size

A total of 116 patients were included in the study.

• Control group: 58 patients
• Tranexamic acid group: 58 patients

The sample size was calculated based on comparison of two means using a two-sided test with 95% confidence interval and 80% power. After applying a 10% buffer, 58 patients were included in each group.

Inclusion Criteria

• Patients aged ≥18 years.
• Patients diagnosed with asymptomatic or minimally symptomatic primary, recurrent, or residual chronic subdural hematoma on CT imaging.
• Patients willing to participate and provide informed consent.
• Patients compliant with follow-up protocol.

Exclusion Criteria

• Hypersensitivity to tranexamic acid.
• Active or history of thromboembolic disorders (deep vein thrombosis, pulmonary embolism, cerebral venous thrombosis, arterial thrombosis, acute coronary syndrome).
• History of stroke, subarachnoid hemorrhage, malignant brain tumors, or seizure disorders.
• Patients requiring immediate revision surgery.
• Severely symptomatic cases requiring urgent surgical intervention.

Procedure and Methodology

After obtaining institutional ethical clearance and informed consent, eligible patients were enrolled. Patients were categorized into two groups as per departmental protocol:

• Group A (Exposure Group): Received oral tranexamic acid 750 mg/day divided into three doses (250 mg thrice daily).
• Group B (Control Group): Managed conservatively without oral tranexamic acid.

Baseline demographic data, comorbidities, neurological status (GCS, Markwalder Grading Score), and CT scan findings were recorded. Hematoma volume was calculated using the ABC/2 method. Midline shift and maximum thickness were measured

All patients were followed up at 4 weeks and 8 weeks in the neurosurgery outpatient department. At each follow-up, neurological examination and CT imaging were performed. Recurrence was defined as radiological re-accumulation of hematoma with or without clinical deterioration requiring intervention. The need for re-surgical procedure was documented.

Adverse events related to tranexamic acid were actively monitored.

Sample Processing

CT brain images were reviewed and hematoma volume was calculated using the standard ABC/2 formula. Radiological parameters including maximum thickness and midline shift were recorded. Neurological scores (GCS, MGS, GOSE) were documented systematically in a structured proforma.

Statistical Methods

Data were entered into Microsoft Excel and analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as frequencies and percentages. Independent sample two-tailed Student’s t-test was used for comparison of continuous variables. Chi-square test was used for categorical variables. A p-value <0.05 was considered statistically significant. Bi-variate and multivariate analyses were performed where appropriate.

Data Collection

Data were collected prospectively using a structured proforma and included: Demographic characteristics (age, gender, income, BMI). Clinical features and comorbidities. Radiological parameters (hematoma volume, thickness, midline shift, laterality, location). Neurological grading (GCS, MGS, GOSE). Recurrence rates. Requirement of re-surgical intervention. Adverse events related to TXA.

Table 1: Baseline Characteristics and Overall Clinical Profile

Table 1 presents the baseline demographic and clinical characteristics of patients in the control and tranexamic acid (TXA) groups. The mean age was comparable between the control group (67.4 ± 9.2 years; 95% CI: 65.0-69.8) and the TXA group (66.8 ± 8.7 years; 95% CI: 64.6-69.0), with no statistically significant difference (p=0.72). A male predominance was observed in both groups, accounting for 70.7% in the control group and 74.1% in the TXA group (p=0.68).

Comorbidities were similarly distributed across both groups. Hypertension was present in 55.2% of controls and 50.0% of TXA patients (p=0.57), while diabetes mellitus was noted in 32.8% and 29.3% of patients, respectively (p=0.69). Antiplatelet usage was also comparable (36.2% vs 39.7%, p=0.70).

Radiological parameters showed no significant baseline differences. The mean hematoma volume was 78.6 ± 18.4 ml in the control group and 76.9 ± 17.9 ml in the TXA group (p=0.63). Similarly, midline shift measurements (5.8 ± 1.9 mm vs 5.6 ± 1.8 mm, p=0.58) and mean Markwalder grade (1.6 ± 0.5 vs 1.5 ± 0.6, p=0.39) were statistically comparable.

Table 2: Recurrence of Chronic Subdural Hematoma

Relative Risk (RR): 0.33; 95% CI of RR: 0.13-0.84; TXA significantly reduced recurrence rates.

Table 2 compares recurrence rates between the two groups. Recurrence occurred in 25.9% (15/58) of patients in the control group (95% CI: 15.5-38.5), compared to only 8.6% (5/58) in the TXA group (95% CI: 2.9-18.7). This difference was statistically significant (p=0.014).

The calculated relative risk (RR) of 0.33 (95% CI: 0.13-0.84) indicates that patients receiving adjunctive TXA had approximately a 67% reduction in the risk of recurrence compared to controls. Conversely, absence of recurrence was observed in 91.4% of TXA patients versus 74.1% of controls.

Table 3: Need for Re-Surgical Intervention

Relative Risk (RR): 0.25; 95% CI of RR: 0.07-0.86; Adjunctive TXA significantly reduced need for repeat surgery.

Table 3 assesses the requirement for repeat surgical intervention during follow-up. Re-surgery was required in 20.7% (12/58) of patients in the control group (95% CI: 11.3-33.4), compared to only 5.2% (3/58) in the TXA group (95% CI: 1.1-14.4). The difference was statistically significant using Fisher’s exact test (p=0.021). The relative risk of 0.25 (95% CI: 0.07-0.86) suggests that adjunctive TXA reduced the risk of requiring repeat surgery by approximately 75%.

Table 4: Radiological and Neurological Outcomes at 4 and 8 Weeks

Table 4 evaluates radiological resolution and functional outcomes. At 4 weeks, the mean hematoma volume was significantly lower in the TXA group (28.7 ± 12.1 ml) compared to controls (41.3 ± 14.6 ml), with strong statistical significance

(p<0.001). This difference persisted at 8 weeks, where hematoma volume further reduced to 10.9 ± 7.2 ml in the TXA group versus 22.6 ± 10.8 ml in controls (p<0.001), demonstrating faster radiological resolution with TXA therapy.

Complete radiological resolution at 8 weeks occurred in 75.9% of TXA patients compared to 50.0% in the control group

(p=0.004). Furthermore, favorable functional outcome (GOSE ≥7) at 8 weeks was significantly higher in the TXA group (86.2%) than in controls (67.2%) (p=0.016).

The present prospective cohort study evaluated the impact of adjunctive oral tranexamic acid (TXA) on recurrence, re-surgical intervention, and radiological as well as neurological outcomes in patients with chronic subdural hematoma (CSDH).

Baseline Characteristics: As shown in Table 1, both study groups were comparable with respect to age, gender distribution, comorbidities, antiplatelet use, baseline hematoma volume, midline shift, and Markwalder grading (p>0.05). The mean age in our study (67 years) is consistent with previous epidemiological reports highlighting CSDH as a disease of the elderly population, particularly those above 65 years, as reported by Musmar B et al. (2024)^[6]. The male predominance observed in our cohort (72%) is also comparable to earlier studies demonstrating a higher incidence in males, possibly due to increased trauma exposure and brain atrophy, as noted by Yang K et al. (2023)^[2].

The prevalence of hypertension and diabetes in our cohort mirrors findings by Pan W et al. (2024)^[4], who identified these comorbidities as common risk factors among CSDH patients. Comparable baseline radiological parameters between groups ensure that the observed differences in outcomes are attributable to TXA therapy rather than confounding clinical severity.

Recurrence Rates: Table 2 demonstrates a statistically significant reduction in recurrence rates in the TXA group (8.6%) compared to the control group (25.9%) (p=0.014), with a relative risk reduction of 67%. This finding aligns with the results of Albalkhi I et al. (2024)^[5], who reported significantly lower recurrence in patients receiving adjunctive TXA. Similarly, Wan KR et al. (2020)^[3] observed decreased recurrence and faster hematoma resolution with antifibrinolytic therapy.

The mechanism underlying this benefit is attributed to inhibition of local hyperfibrinolysis within the neomembrane of CSDH, thereby preventing recurrent microbleeding. A study by Messias BR et al. (2025)^[7] also supported the role of TXA in reducing recurrence, although heterogeneity among studies was noted. The recurrence rate in our control group (25.9%) is comparable to historical recurrence rates ranging between 10-30%, as reported in earlier neurosurgical series.

Need for Re-Surgical Intervention: Table 3 further demonstrates that adjunctive TXA significantly reduced the need for repeat surgery (5.2% vs 20.7%, p=0.021), with a relative risk of 0.25. These findings corroborate those of Ali SM et al. (2024)^[8], who suggested that medical adjuncts may decrease surgical re-intervention in selected patients. The reduction in re-surgery is clinically significant, particularly in elderly individuals with multiple comorbidities, where repeated anesthesia and surgical stress increase morbidity.

The lower re-operation rates observed in the TXA group likely reflect both reduced recurrence and enhanced hematoma resorption, highlighting the therapeutic potential of antifibrinolytic agents as an adjunct to conservative or post-operative management.

Radiological and Neurological Outcomes: Table 4 shows significantly faster hematoma resolution in the TXA group at both 4 and 8 weeks (p<0.001). Complete radiological resolution at 8 weeks was achieved in 75.9% of TXA patients compared to 50.0% of controls (p=0.004). These findings are consistent with Stubbs DJ et al. (2022)^[9], who reported accelerated reduction in hematoma volume with TXA therapy.

Moreover, functional outcomes assessed by GOSE ≥7 were significantly better in the TXA group (86.2% vs 67.2%, p=0.016). Improved neurological recovery may be attributed to faster hematoma clearance and reduced recurrence-related neurological deterioration. Shibahashi K et al. (2022)^[10] emphasized that recurrence adversely affects functional outcomes, which further supports the beneficial impact of recurrence reduction through TXA therapy.

The present prospective cohort study demonstrates that adjunctive oral tranexamic acid (TXA) significantly reduces recurrence rates and the need for re-surgical intervention in patients with chronic subdural hematoma (CSDH). Patients receiving TXA showed a marked reduction in recurrence (8.6% vs 25.9%) and repeat surgery (5.2% vs 20.7%) compared to the control group. In addition, TXA therapy was associated with faster radiological resolution of hematoma and improved functional neurological outcomes at 8 weeks.

These findings support the role of antifibrinolytic therapy as a safe and effective adjunct in the management of asymptomatic or minimally symptomatic CSDH. By reducing recurrence and surgical re-intervention, TXA may decrease morbidity, hospital stay, and healthcare burden, particularly in elderly patients with multiple comorbidities. Larger randomized controlled trials with longer follow-up are recommended to confirm these results and establish standardized treatment guidelines.

LIMITATIONS OF THE STUDY

1. The study was conducted at a single tertiary care center, which may limit generalizability.
2. The sample size, although adequate for primary outcomes, was relatively small.
3. Allocation was based on departmental protocol rather than randomized assignment, introducing potential selection bias.
4. Follow-up duration was limited to 8 weeks; late recurrences may not have been captured.
5. Blinding was not performed, which may introduce observational bias.
6. Long-term safety profile of prolonged TXA use was not extensively evaluated.
7. Functional outcomes were assessed using GOSE, but detailed quality-of-life measures were not included.

1. de Paula MV, Ribeiro BD, Melo MM, de Freitas PV, 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. Neurosurgical Review. 2023 Apr 18;46(1):90.
2. Yang K, Kim KH, Lee HJ, Jeong EO, Kwon HJ, Kim SH. Role of adjunctive tranexamic acid in facilitating resolution of chronic subdural hematoma after surgery. Journal of Korean Neurosurgical Society. 2023 Jul 1;66(4):446-55.
3. Wan KR, Qiu L, Saffari SE, Khong WX, Ong JC, See AA, Ng WH, King NK. An open label randomized trial to assess the efficacy of tranexamic acid in reducing post-operative recurrence of chronic subdural haemorrhage. Journal of Clinical Neuroscience. 2020 Dec 1;82:147-54.
4. 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. Frontiers in Neurology. 2024 Apr 22;15:1359354.
5. Albalkhi I, Alaswad M, Saleh T, Senjab A, Helal B, Khan JA. Adjuvant tranexamic acid for reducing postoperative recurrence of chronic subdural hematoma in the elderly: a systematic review and meta-analysis. World Neurosurgery. 2024 Feb 1;182:e829-36.
6. Musmar B, Orscelik A, Salim H, Adeeb N, Spellicy S, Abdelgadir J, Azar J, Cuellar-Saenz HH, Guthikonda B, Jabbour P, Hasan D. Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma: a systematic review and meta-analysis. Journal of Neurosurgery. 2024 Apr 5;141(4):945-54.
7. Messias BR, Borges JP, Gentil AF. Chronic subdural hematoma and tranexamic acid: a systematic review. Turk Neurosurg. 2025;35(4):527-36.
8. Ali SM, Haseeb A, Shafique MA, Mustafa MS, Kumar A, Nasir R, Azhar MA, Ahmad TK, Raja A, Raja S, Lucke-Wold B. Examining the standalone efficacy and safety of tranexamic acid in chronic subdural hematoma: a comprehensive review and meta-analysis. Egyptian Journal of Neurosurgery. 2024 Nov 8;39(1):65.
9. Stubbs DJ, Davies BM, Menon DK. Chronic subdural haematoma: the role of peri‐operative medicine in a common form of reversible brain injury. Anaesthesia. 2022 Jan;77:21-33.
10. 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. Journal of Neurosurgery. 2022 Jul 22;138(2):430-6.