The Role of Tranexamic Acid (TXA) In Spine Surgeries: A Systematic Review
- 1. Department of Surgery, Iraq
- 2. Department of Neuroscience, Saint Georges Hospital, London
Almahfoodh AB, Lui DF, Hamdan TA (2021) The Role of Tranexamic Acid (TXA) In Spine Surgeries: A Systematic Review. J Surg Transplant Sci 8(1): 1083.
Tranexamic Acid (TXA)
Tranexamic acid (TXA) was first made in 1962 by Japanese researchers Shosuke and Utako Okamoto. 
Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, preventing fibrin degradation and preserving the framework of fibrin’s matrix structure. 
It can be administered through several routes ,orally, topically, or intravenously, and has a 100% bioavailability 
Intravenous administration results in peak levels within minutes. The average half-life (time needed for half the active drug to be eliminated from the body) is two hours following intravenous administration and up to 12 hours following oral administration. 
95% of Tranexamic acid is excreted unchanged in the urine and only small amount is metabolized by the Liver.
Dosing Dosing of TXA differs according to the Indication, but regarding it’s usage in Spine Surgeries Previous studies have demonstrated the clinically effective intravenous dose to be 10-15 mg/kg of body weight, with higher dosages providing diminishing benefits.
A topical TXA irrigation is typically poured into the surgical field before wound closure, with dosing protocols ranging from 10 mg/kg (i.e., around 1 g) to 3 g of tTXA in saline solution. 
Tranexamic acid is frequently used following major trauma . Tranexamic acid is used to prevent and treat blood loss in a variety of situations, such as dental procedures for hemophiliacs, heavy menstrual bleeding, and surgeries with high risk of blood loss. [4-5] it is also used in orthopedic surgery to reduce blood loss, to the extent of reducing or altogether abolishing the need for perioperative blood collection. It is of proven value in clearing the field of surgery and reducing blood loss when given before or after surgery. Drain and number of transfusions are reduced. 
• Allergy to tranexamic acid.
• History of seizures.
• History of venous or arterial thromboembolism or active thromboembolic disease.
• Severe kidney impairment due to accumulation of the medication, so dose adjustment is required in mild or moderate kidney impairment. 
Side effects are rare.  Some include changes in color vision, blood clots, and allergic reactions. Blood clots may include venous thromboembolism (deep vein thrombosis and pulmonary embolism), anaphylaxis.  These rare side effects were reported in post marketing experience and frequencies cannot be determined.  Despite the mode of action, large studies of the use of tranexamic acid have not shown an increase in the risk of venous or arterial thrombosis. 
Massive blood loss occurs frequently and remains a challenge in spinal surgery.  Significant intra- and postoperative hemorrhage negatively affects patient outcomes by increasing coagulopathy, postoperative hematoma, and anemia.  The need for allogenic blood transfusions can lead to potential transfusion reactions and infections, in addition to increasing long-term mortality rates. There is an economic disadvantage associated with iatrogenic major blood loss relating to the direct costs of the blood products and intraoperative blood salvage technology and indirect costs of prolonged patient hospitalization and complication management.
There are actually increasing numbers of clinical trials and retrospective studies investigating the role of TXA in spine surgeries, using different doses, different methods of administration and on different types Surgeries , THIS Meta -Analysis is directed towards finding the missing points regarding those Studies , and hopefully will guide us towards a more targeted research regarding this topic in the future to help overcome the limitations of TXA use in Spine Surgeries perse and orthopedic practice in general.
The systematic review was written by in guidance of an adapted version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
An electronic database search was conducted on PubMed and Cochrane electronic databases. As seen in (Figure 1), the search terms “The Role of Tranexamic Acid in Spine Surgeries” were crucial in our database search in enabling us to find articles relevant to our inclusion criteria (which is detailed below)
1-The population of the Study Should be patients undergoing Spine surgeries regardless the Type.
2-Only Tranexamic acid must be used and no other antifibrinolytic agent regardless the method of administration.
3-Studies designed to find the effect of TXA on intra and/or postoperative Bleeding and /or the need for postoperative blood Transfusion.
xclusion Criteria :
1-Meta analysis Designed Studies.
2-Studies and trials in which other Antifibrinolytic agents were used.
|No||Authors||Article title||Method of Administration||Type of spine surgery||Result &conclusion|
|1||A Randomized Controlled Trial of Low-Dose Tranexamic Acid versus Placebo to Reduce Red Blood Cell Transfusion During Complex Multilevel Spine Fusion Surgery(17).||IV TXA (10 mg/kg loading dose, then 1 mg/kg/ hr throughout surgery)||Complex Multilevel Spine Fusion Surgery||Our results support the use of low-dose tranexamic acid during complex multilevel spine fusion surgery to decrease total red blood cell transfusion.|
|2||A Randomized Controlled Trial of Topical Application of Tranexamic Acid in Patients with Thoracolumbar Spine Trauma Undergoing Long-Segment Instrumented Posterior Spinal Fusion(18).||solution containing 1 g of TXA (20 mL) was applied to the site of surgery via a drain tube after the spinal fascia was closed, and then the drain was clamped for 2 hours.||Long-Segment Instrume-nted Posterior Spinal Fusion||The use of topically administered 1 g TXA in thoracic and lumbar spinal trauma cases effectively decreased postoperative transfusion requirements and minimized postoperative blood loss, as determined by the total drainage volume.|
|3||Can tranexamic acid reduce blood loss in cervical laminectomy with lateral mass screw fixation and bone grafting: a retrospective observational study(19).||IV TXA.||cervical laminectomy with lateral mass screw fixation and bone grafting||Total blood loss in the TXA group was significantly lower than that of the control group.|
|4||Clinical Research of Combined Intravenous Administration and Topical Application of Tranexamic Acid to a Surgical Wound During Posterior Lumbar Fusion(20).||IV And topical TXA.||double-segment posterior lumbar decompression and fusion surgery||Combined intravenous and topical administration of TXA seems to be effective and safe in reducing allogenic blood transfusion and blood loss in doublesegment posterior lumbar decompression and fusion surgery|
|5||Cost-benefit analysis of tranexamic acid and blood transfusion in elective lumbar spine surgery for degenerative pathologies (21).||IV TXA.||elective lumbar spine surgery for degenerati-ve pathologie-s.||TXA use was associated with decreased intraoperative blood loss and significant reductions in total hemostasis costs for patients undergoing surgery on more than 4 levels.|
|6||Different Effects of Intravenous, Topical, and Combined Application of Tranexamic Acid on Patients with Thoracolumbar Fracture (22).||IV , Topical and Combined TXA.||thoracolumbar fracture fixation with percutaneous pedicle screw.||Preoperative intravenous drip of TXA can remarkably reduce intraoperative HBL and IBL in patients with thoracolumbar fracture fixed with percutaneous pedicle screw.|
|7||Does Prophylactic Administration of TXA Reduce Mean Operative Time and Postoperative Blood Loss in Posterior Approach Lumbar Spinal Fusion Surgery Performed for Degenerative Spinal Disease?(23).||IV TXA.||Lumbar Spinal Fusion Surgery Performed for Degenerative Spinal Disease.||In the present study, perioperative TXA administration was associated with reduced postoperative drain output and surgical time.|
|8||Does Tranexamic Acid Reduce Perioperative Bleeding in Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures?(24).||10 mg/kg of TXA 30 minutes intravenously before skin incision and 3 hours post-operative and oral medication for three days||Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures.||Administration of TXA before surgery significantly reduces perioperative bleeding in patients undergoing short segment pedicle screw fixation for thoracolumbar spine fractures.|
|9||Double-blind, randomized controlled trial of tranexamic acid in minor lumbar spine surgery: no effect on operative time, intraoperative blood loss, or complications(25).||IV TXA (10 mg/kg).||minor lumbar decompressive surgery.||Tranexamic acid did not have a statistically significant effect on operative time, intraoperative blood loss, or complications.|
|10||Effectiveness and Safety of Tranexamic Acid in Spinal Deformity Surgery(26).||IV TXA.||spinal deformity surgery||TXA use can effectively reduce the amount of intraoperative bleeding and transfusion requirements in spinal deformity surgery.|
|11||Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, doubleblind, placebo-controlled study(27).||Patients received either TA or placebo as a loading dose of 2 g (for adults) or 30 mg/kg (for children), followed immediately by continuous infusion of 100 mg/h (for adults) or 1 mg/ kg/h (for children) during surgery and for 5 hours after the operation.||Eighteen patients had multilevel anterior cervical discectomies with or without internal fixation, 22 patients had decompressive surgery (12 laminectomies and 10 intersegmental decompressions) for multisegment spinal stenosis, 15 patients had laminectomy with posterior spinal fixation, and remaining 9 patients had laminectomy and excision of spinal tumor.||Prophylactic use of large doses of TA provides an effective, safe, and cheap method for reducing blood loss during and after spinal operations.|
|12||Efficacy and Safety of Topical Use of Tranexamic Acid in Reducing Blood Loss During Primary Lumbar Spinal Surgery: A Retrospective Case Control Study(28).||Wound surface was soaked with TXA (1 g in 100 mL saline solution) for 5 minutes before wound closure.||Posterior lumbar spinal fusion surgery||Topical TXA can significantly reduce postoperative blood loss, accelerate removal of drainage tube, shorten the duration of hospital stay, while not increasing the complication incidence in patients undergoing posterior lumbar spinal 13fusion surgery.|
|13||Efficacy of prophylactic low dose of tranexamic acid in spinal fixation surgery: a randomized clinical trial (29).||TXA (10 mg/kg) at the initiation of induction of anesthesia during 10 min followed by intravenous infusion of 1 mg/kg/h.||Spinal fixation surgeries.||The administration of a prophylactic low dose of TXA did not have a significant effect in the management of intraoperative blood loss and transfusion requirements in patients undergoing spinal fixation surgery|
|14||Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study(30).||patients received 1 g tranexamic acid intravenous, preoperative and six hours and twelve hours postoperative.||posterior lumbar spine surgery for degenerative spinal stenosis with instability.||This study suggests a less blood loss when administering tranexamic acid in posterior lumbar spine surgery as demonstrated by the higher postoperative hemoglobin concentration and the less blood loss.|