Investigating the Effect of Tranexamic Acid on the Treatment of Subdural Hematoma: A Systematic Review Study

authors:

avatar Masoud Hatefi ORCID 1 , avatar Khalil Komlakh ORCID 2 , *

Clinical Research Development, Imam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
Department of Neurosurgery, School of Medicine Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

how to cite: Hatefi M, Komlakh K. Investigating the Effect of Tranexamic Acid on the Treatment of Subdural Hematoma: A Systematic Review Study. Arch Neurosci.9(3):e127011. doi: 10.5812/ans-127011.

Abstract

Context:

Tranexamic acid (TXA) belongs to the family of lysine-derived antifibrinolytics. TXA requires a simple molecular breakdown in the liver to be metabolized and has a high renal excretion.

Objectives:

This study aimed to determine the effect of TXA on subdural hematoma (SDH) treatment using the SR method.

Methods:

Following a systematic review design, this study aimed to evaluate the effect of TXA on SDH treatment using studies published from 2000 to 2020. The search was performed by two researchers who were dominant in various types of SR studies and specialized discussion of neurosurgery. A checklist that contained the following items was used to collect the data: surname, year of study, year of publication, population, sample size, age, intervention, and outcomes. Data were also classified and reported using Word software.

Results:

Initially, 178 articles were identified, out of which 118 were removed due to the relevance of the title and method, 44 due to duplication, six due to following the SR method, and three due to having a case report design. Seven studies were found as eligible, as follows: the study by Wakabayashi et al. with a sample of 199 patients, Kageyama et al.’s study with 21 patients, Wan et al.’s study with 90 patients, Kutty et al.’ study with 27 patients, Tanweer et al.’s study with 14 patients, Yamada et al.’s study with 193 patients, and Lodewijkx et al.’s study with 7 patients. All articles showed that TXA could reduce SH.

Conclusions:

Regarding the positive effect of TXA on reducing SDH, administration of this medicine is recommended in the treatment of patients with CSDH.

1. Context

Head trauma is one of the most costly sections of health care in European countries. The World Health Organization estimated that approximately 90% of mortality due to trauma occurs in low- and middle-income countries (1-3). Each year, about 1.5 million people die due to brain trauma and about 10 million people are hospitalized due to this type of traumas (4). Preventive measures seem to play an important role in managing treatment and preventing further complications in these patients (5).

Attention to patients is essential (6-9). Chronic subdural hematoma is a common hemorrhage in the intracranial space, consisting of blood serum and decomposed blood products. Blood in the subdural space leads to an inflammatory reaction and the cascade progression of the disease. This type of hematoma may be due to trauma, as the most important and common cause, coagulation disorders, arachnoid cyst, vascular disorders, metastatic cancers, and brain meningioma (10, 11). Chronic subdural hematoma (CSDH) is an important hemorrhage that occurs after head trauma, which is considered the most important treatable cause of death and disability in trauma victims in almost half of the patients injured with severe trauma (12). Surgery is one of the most important treatments used for these patients. On the other hand, various medicines, such as ACE inhibitors (13), steroids (14), tranexamic acid (15), and herbal medicines (16), are used along with surgery.

Tranexamic acid (TXA) belongs to the family of lysine-derived antifibrinolytics. TXA requires a simple molecular breakdown in the liver to be metabolized and has a high renal excretion (3). TXA is an anti-fibrinolytic agent and a synthetic lysine-derived reducing hemorrhage through reversible competition for the lysine junction in plasminogen with fibrin. This medicine further inhibits the activation of plasminogen and prevents the destruction of fibrin by plasmin (17, 18). The TXA antifibrinolytic power is higher than the existing antifibrinolytic medicines while it has the fewest side effects. TXA does not increase thromboembolic complications such as deep vein thrombosis and pulmonary embolism (19, 20).

Medication can improve patients' condition (3, 21, 22). Antifibrinolytic medicines improve homeostasis, reduce hemorrhage, and consequently reduce the need for blood transfusions. These medicines have been addressed in various surgeries such as cardiovascular, liver, and orthopedic surgeries (19, 23-25). One of these medicines is TXA, the effects of which have been shown in various surgeries (26).

2. Objectives

Given the importance of identifying an effective medicine for reducing the status of subdural hematoma (SDH), this study aimed to determine the effect of TXA on SH treatment using the SR method.

3. Methods

3.1. Study Protocol

This SR study was conducted to evaluate the effect of tranexamic acid on SH treatment using articles published from 2000 to 2020.

3.2. Search Strategy and Study Selection

The search was performed by two researchers who were dominant in various types of SR studies and specialized discussion of neurosurgery. Table 1 presents the searched databases. The search method was according to PICO criteria, which are presented in Table 2 (Tables 1 and 2).

Table 1. Included Databases
Status of included databasesName of database
NationalSID, Iran Doc, RICST
InternationalWeb of Science, Science Direct, Scopus, Embase, PubMed/Medline, EBSCO, CINAHL, Cochrane Library, EMBASE.
Table 2. Search Terms
Search TermBoolean Keywords
Outcome termsubdural hematoma
Population termPatients with subdural hematoma
Descriptive termTranexamic acid OR subdural hematoma OR chronic subdural hematoma OR subdural OR Recurrence OR Medical treatment

3.3. Inclusion and Exclusion Criteria

A checklist that contained the following items was used to collect the data: surname, year of study, year of publication, population, sample size, age, intervention, and outcomes. Data were also classified and reported using Word software.

3.4. Data Extraction

The checklist contained information on surname, year of study, year of publication, population, sample size, age, intervention, and outcomes. Data were also classified and reported using Word software.

4. Results

4.1. Search Results and Features

Initially, 178 articles were identified, out of which 118 were removed due to the relevance of the title and method, 44 due to duplication, six due to following the SR method, and three due to having a case report design.

4.2. Demographic Characteristics Articles Reviewed

Seven studies were found as eligible, as follows: the study by Wakabayashi et al. (27) with a sample of 199 patients, Kageyama et al.’s study (28) with 21 patients, Wan et al.’s study (29) with 90 patients, Kutty et al.’ study (30) with 27 patients, Tanweer et al.’s study (31) with 14 patients, Yamada et al.’s study (32) with 193 patients, and Lodewijkx et al.’s study (33) with 7 patients (Table 3).

Table 3. Specifications of Articles Entered in the Systematic Review
RowAuthorYearStudy DesignPopulationNAge aInterventionOutcomes
1Wakabayashi et al. (27)2012-CSDH19977.7 ± 10.5Patients were given Gorei-san, TXA, and a combination of these two medicines.The recurrence rate was 8.3% in patients treated with Gorei-san, 10.9% in patients receiving TXA, 2.9% in patients with a combination of the two medicines, and 5.7% in patients without medication.
2Kageyama et al. (28)2013Clinical articleCSDH2179 Years750 mg of orally every dayBefore treatment with TXA, the hematoma was 58.5 mL, which decreased to 3.7 mL after TXA. Also, hematoma did not recur or progress in any of the patients.
3Wan et al. (29)2020Clinical articleCSDH90-500 mg/twice dayThe use of TXA can reduce SDH.
4Kutty et al. (30)2019Prospective Observational StudyCSDH2739-87 years750 mg/dayThe recovery rate of hematoma in patients was appropriate, and no progress was reported in any of the patients in terms of increased hematoma severity. Generally, TXA is an effective medicine in reducing hematoma status in patients with CSDH.
5Tanweer et al. (31)2019RetrospectiveSDH1456.4 ± 16.3650 mg daily orallyThere was no increase or delayed recurrence of SDH during TXA treatment. There was also no thromboembolism in the patients. The average volume decreased from 9.44 ± 4.84 mm to 4.44 ± 3.29 mm.
6Yamada et al. (32)2020prospective studyCSDH193TXA Group: 78.2 ± 9.8; Goreisan Group: 79.2 ± 8.7750 mg of orallyMean (standard deviation) of hematoma in ml in the TXA group decreased from 108.1 (39.5) before intervention to 39.4 (23.2) on the day after intervention, 9.8 (16) 2 months after intervention and 5.6 (12.4) in 3 months after the intervention. While in the no-administration group, it decreased from 109.2 (38.7) before intervention to 36.8921.9) on the day after intervention, 17.9 (20) two months after intervention and 11 (16.5) three months after the intervention. Generally, the remaining hematoma volume in the TXA group was less than in other groups in 1, 2, and 3 months.
7Lodewijkx et al. (33)2021prospectivelyCSDH778 Years500 mg twice dailyThe recurrence rate was 8.3% in patients treated with Gorei-san, 10.9% in patients receiving TXA, 2.9% in patients with a combination of the two medicines, and 5.7% in patients without medication.

4.3. Role of TXA in Reducing SH

All studied articles showed that TXA could reduce SDH.

As shown in Figure 1, initially, 173 articles were extracted, of which seven were found as eligible (Figure 1). All articles were on patients with CSDH, and published from 2012 to 2021. In all articles that included the SR phase, TXA could reduce SDH.

5. Discussion

According to the findings, TXA could reduce SDH. Given the fact that no SR article has been conducted on the effect of TXA on SDH reduction, the findings are compared with other related articles. Two articles have investigated the TXA effect on hemorrhage reduction following the SR design. Gluud et al. investigated seven articles with a total of 1754 patients to evaluate the effect of TXA on the status of gastrointestinal hemorrhages, and showed that TXA could reduce hemorrhages in the upper gastrointestinal tract (34). In the same vein, Lee et al. performed an SR study (13 articles with a sample size of 2271 cases) and indicated that TXA could reduce continued bleeding, mortality, and urgent endoscopic intervention (35), which is consistent with the results of this study. TXA is a cheap and affordable medicine that can reduce the rate of hemorrhage and, consequently, the accessibility and need for blood, which has been shown to be effective in a variety of surgeries, including spine, obstetrics, plastic, and chest surgery (36, 37). In an SR study published by Scarafoni, with 23 articles in which TXA was prescribed to plastic surgery patients, it was indicated that TXA reduced hemorrhage, edema, and postoperative ecchymosis in plastic surgery patients (36).

Also, in an SR study published by Lee et al. with 11 articles in which TXA was prescribed to 1842 patients, it was shown that TXA could reduce operative time, postoperative hemorrhage, complications, and hospital stays in patients undergoing surgery with PCNL (38). Zhang et al. performed another SR study on the status of TXA on hemorrhage, with 13 articles in which TXA was prescribed to patients with femoral fracture surgery, and reported that it could reduce transfusion rate (39), which is consistent with the results of this SR study on the positive effect of TXA on patients with SDH.

Given the fact that the effect of TXA on patients with different medical diagnoses has been evaluated in various articles, so far, no study has investigated the effect of TXA on SDH, and this issue has been considered for the first time in this study. Therefore, conducting this study is a strength. One of the limitations of this study is the lack of meta-analysis in this field, which is suggested to be performed on recently published articles.

5.1. Conclusions

According to the positive effect of TXA on reducing SDH, the administration of this medicine is recommended to treat patients with CSDH.

References

  • 1.

    Rizevandi P, Alimohammadi E, Bagheri SR, Abdi A, Veisi H. [The impact of preinjury consumption of antithrombotic drugs on clinical outcomes of patients with moderate to severe traumatic brain injury]. Scientific Journal of Nursing, Midwifery and Paramedical Faculty. 2020;5(4):94-104. Persian.

  • 2.

    Hayati S, Yazdani R, Ghasemi A, Yousefi Kafshgari M, Tabibzadeh Dezfuli SA. Epidemiology and radiologic findings of patients with traumatic brain injuries in emergency department of Shahid Mohammadi hospital. Eurasian Chem Commun. 2020;2(12):1210-5. doi: 10.22034/ECC.2020.253265.1086.

  • 3.

    Abdullah JN, Mohammed SB, Al-auqbi TF. Evaluation of the osteoprotegerin and insulin levels in patient's serum with hypothyroid and hypothyroid with type 2 diabetes mellitus. Eurasian Chemical Communications. 2021;3(11):854-9. doi: 10.22034/ecc.2021.298959.1210.

  • 4.

    Bruns J, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44(s10):2-10. doi: 10.1046/j.1528-1157.44.s10.3.x. [PubMed: 14511388].

  • 5.

    Tabesh H, Rezvani M, Salehi S. [The effect of tranexamic acid on traumatic brain hematomas]. J Isfahan Med Sch. 2016;34(381):378-83. Persian.

  • 6.

    Khalil Arjmandi R, Asharein MR. Case Study of Femoral and Radial Angiography in Cardiovascular Patients. Chem Methodol. 2020;5(1):1-10.

  • 7.

    Yazdani R, Hayati S, Yousefi Kafshgari M, Ghasemi A, Tabibzadeh Dezfuli SA. Epidemiology and Radiologic Findings of Patients with Traumatic Spine Injures in Iran: Methodological and Epidemiological Study. Chem Methodol. 2020;5(1):35-40.

  • 8.

    Tabibzadeh Dezfuli SA, Yazdani R, Yarmoradi J, Banar M, Hayati S. Comparison of the ultrasonography report by the emergency service with radiology service in suspected DVT patients: A Cross-sectional study for investigation about pharmaceutical and therapeutic interventions. Eurasian Chem Commun. 2020;2(2):181-6. doi: 10.33945/sami/ecc.2020.2.3.

  • 9.

    Sadeghi Pour E, Hayati S, Khorasani MJ, Tabibzadeh Dezfuli SA. Effect of Hbs on accuracy of pulse oximetry in blood oxygen saturation level measurement among adult patients with sickle cell disease. Eurasian Chem Commun. 2020;2(3):296-301. doi: 10.33945/sami/ecc.2020.3.1.

  • 10.

    Feghali J, Yang W, Huang J. Updates in Chronic Subdural Hematoma: Epidemiology, Etiology, Pathogenesis, Treatment, and Outcome. World Neurosurg. 2020;141:339-45. doi: 10.1016/j.wneu.2020.06.140. [PubMed: 32593768].

  • 11.

    Shim YS, Park CO, Hyun DK, Park HC, Yoon SH. What are the causative factors for a slow, progressive enlargement of a chronic subdural hematoma? Yonsei Med J. 2007;48(2):210-7. doi: 10.3349/ymj.2007.48.2.210. [PubMed: 17461518]. [PubMed Central: PMC2628130].

  • 12.

    Fakharian E, Fazel MR, Tabesh H, Ghaffarpasand I. [Incidence of multiple intracranial hematomas in Kashan Shahid Beheshti hospital (2006-2008)]. KAUMS Journal (FEYZ). 2009;12(5):7-10. Persian.

  • 13.

    Weigel R, Hohenstein A, Schlickum L, Weiss C, Schilling L. Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism. Neurosurgery. 2007;61(4):788-93. doi: 10.1227/01.NEU.0000298907.56012.E8. [PubMed: 17986940].

  • 14.

    Thotakura AK, Marabathina NR. Nonsurgical Treatment of Chronic Subdural Hematoma with Steroids. World Neurosurg. 2015;84(6):1968-72. doi: 10.1016/j.wneu.2015.08.044. [PubMed: 26342776].

  • 15.

    Yogendrakumar V, Wu TY, Churilov L, Tatlisumak T, Strbian D, Jeng JS, et al. Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial. Eur Stroke J. 2022;7(1):15-9. doi: 10.1177/23969873211072402. [PubMed: 35300248]. [PubMed Central: PMC8921778].

  • 16.

    Miyagami M, Kagawa Y. [Effectiveness of Kampo medicine Gorei-San for chronic subdural hematoma]. No Shinkei Geka. 2009;37(8):765-70. Japanese. [PubMed: 19663334].

  • 17.

    Levine BR, Haughom B, Strong B, Hellman M, Frank RM. Blood management strategies for total knee arthroplasty. J Am Acad Orthop Surg. 2014;22(6):361-71. doi: 10.5435/JAAOS-22-06-361. [PubMed: 24860132].

  • 18.

    Fakoor M, Moosavi S, Hatami Joni S. The effect of Tranexamic Acid on Blood Loss and Hospital-Stay after Knee Replacement Surgery. Iran J Orthop Surg. 2020;18(4):590-3. doi: 10.4103/0019-5049.90614. [PubMed: 22223903]. [PubMed Central: PMC3249866].

  • 19.

    Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009;123(5):687-96. doi: 10.1016/j.thromres.2008.09.015. [PubMed: 19007970].

  • 20.

    Gillette BP, DeSimone LJ, Trousdale RT, Pagnano MW, Sierra RJ. Low risk of thromboembolic complications with tranexamic acid after primary total hip and knee arthroplasty. Clin Orthop Relat Res. 2013;471(1):150-4. doi: 10.1007/s11999-012-2488-z. [PubMed: 22814857]. [PubMed Central: PMC3528901].

  • 21.

    Hayati S, Yazdani R, Esmaeili M, Kazemi S, Tabibzadeh Dezfuli SA. Comparative effect of propofol versus fentanyl in controlling acute renal colic and its hydronephrosis in patients admitted to the hospital. Eurasian Chem Commun. 2020;2(5):604-8. doi: 10.33945/SAMI/ECC.2020.5.6.

  • 22.

    Sadeka AH, Babanb RS, Al-Habibc MF, Khazaalid EA. Assessment of serum afamin in patients with preeclampsia at third trimester. Eurasian Chem Commun. 2021;3:622-6.

  • 23.

    Colomina MJ, Bago J, Vidal X, Mora L, Pellise F. Antifibrinolytic therapy in complex spine surgery: a case-control study comparing aprotinin and tranexamic acid. Orthopedics. 2009;32(2):91. [PubMed: 19301800].

  • 24.

    Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;(3). CD001886. doi: 10.1002/14651858.CD001886.pub4. [PubMed: 21412876]. [PubMed Central: PMC4234031].

  • 25.

    Ickx BE, van der Linden PJ, Melot C, Wijns W, de Pauw L, Vandestadt J, et al. Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation. Transfusion. 2006;46(4):595-605. doi: 10.1111/j.1537-2995.2006.00770.x. [PubMed: 16584436].

  • 26.

    Mosaffa F, Kazemi SM, Kaffashi M, Eajazi A, Daftari Besheli L, Bigdeli MR, et al. [The Effect of Pre-operative Tranexamic Acid on Blooding Prevention in Non-Cemented Hip Arthroplasty]. Iranian Journal of Orthopedic Surgery. 2020;7(3):114-20. Persian.

  • 27.

    Wakabayashi Y, Yamashita M, Asano T, Yamada A, Kenai H, Kondoh Y, et al. [Effect of Gorei-san with tranexamic acid for preventing recurrence of chronic subdural hematoma]. No Shinkei Geka. 2012;40(11):967-71. Japanese. [PubMed: 23100384].

  • 28.

    Kageyama H, Toyooka T, Tsuzuki N, Oka K. Nonsurgical treatment of chronic subdural hematoma with tranexamic acid. J Neurosurg. 2013;119(2):332-7. doi: 10.3171/2013.3.JNS122162. [PubMed: 23641825].

  • 29.

    Wan KR, Qiu L, Saffari SE, Khong WXL, Ong JCL, See AA, et al. 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. doi: 10.1016/j.jocn.2020.10.053. [PubMed: 33317724].

  • 30.

    Kutty RK, Leela SK, Sreemathyamma SB, Sivanandapanicker JL, Asher P, Peethambaran A, et al. The Outcome of Medical Management of Chronic Subdural Hematoma with Tranexamic Acid - A Prospective Observational Study. J Stroke Cerebrovasc Dis. 2020;29(11):105273. doi: 10.1016/j.jstrokecerebrovasdis.2020.105273. [PubMed: 33066896].

  • 31.

    Tanweer O, Frisoli FA, Bravate C, Harrison G, Pacione D, Kondziolka D, et al. Tranexamic Acid for Treatment of Residual Subdural Hematoma After Bedside Twist-Drill Evacuation. World Neurosurg. 2016;91:29-33. doi: 10.1016/j.wneu.2016.03.062. [PubMed: 27032521].

  • 32.

    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. doi: 10.1016/j.wneu.2019.10.134. [PubMed: 31678452].

  • 33.

    Lodewijkx R, Immenga S, van den Berg R, Post R, Westerink LG, Nabuurs RJA, et al. Tranexamic acid for chronic subdural hematoma. Br J Neurosurg. 2021;35(5):564-9. doi: 10.1080/02688697.2021.1918328. [PubMed: 34334070].

  • 34.

    Gluud LL, Klingenberg SL, Langholz SE. Systematic review: tranexamic acid for upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2008;27(9):752-8. doi: 10.1111/j.1365-2036.2008.03638.x. [PubMed: 18248659].

  • 35.

    Lee PL, Yang KS, Tsai HW, Hou SK, Kang YN, Chang CC. Tranexamic acid for gastrointestinal bleeding: A systematic review with meta-analysis of randomized clinical trials. Am J Emerg Med. 2021;45:269-79. doi: 10.1016/j.ajem.2020.08.062. [PubMed: 33041136].

  • 36.

    Elena Scarafoni E. A Systematic Review of Tranexamic Acid in Plastic Surgery: What's New? Plast Reconstr Surg Glob Open. 2021;9(3). e3172. doi: 10.1097/GOX.0000000000003172. [PubMed: 33907653]. [PubMed Central: PMC8062149].

  • 37.

    Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2017;376(2):136-48. doi: 10.1056/NEJMoa1606424. [PubMed: 27774838].

  • 38.

    Lee MJ, Kim JK, Tang J, Ming JM, Chua ME. The Efficacy and Safety of Tranexamic Acid in the Management of Perioperative Bleeding After Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis of Comparative Studies. J Endourol. 2022;36(3):303-12. doi: 10.1089/end.2021.0498. [PubMed: 34569280].

  • 39.

    Zhang P, Bai J, He J, Liang Y, Chen P, Wang J. A systematic review of tranexamic acid usage in patients undergoing femoral fracture surgery. Clin Interv Aging. 2018;13:1579-91. doi: 10.2147/CIA.S163950. [PubMed: 30233155]. [PubMed Central: PMC6130291].

Copyright © 2022, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.