Overview
Definition:
Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine that acts as an antifibrinolytic agent
It competitively inhibits the activation of plasminogen to plasmin, thereby preventing the breakdown of fibrin clots
This action reduces bleeding in various surgical settings
Its mechanism involves binding to the lysine binding sites of plasminogen, blocking its access to fibrin, and thus stabilizing the clot
In surgical practice, TXA is primarily used to reduce perioperative blood loss and the need for blood transfusions.
Epidemiology:
Surgical bleeding remains a significant concern, impacting patient outcomes, hospital stays, and healthcare costs
Studies indicate that a substantial proportion of patients undergoing major surgery may experience significant blood loss
The incidence of needing blood transfusions varies by surgical specialty and patient factors, with higher rates seen in complex procedures
The widespread adoption of TXA has demonstrated its efficacy in reducing these complications across diverse surgical disciplines.
Clinical Significance:
Effective management of surgical bleeding is paramount for patient safety and successful surgical outcomes
Uncontrolled hemorrhage can lead to hypovolemic shock, organ damage, prolonged operative times, increased ICU stays, and higher mortality rates
Tranexamic acid offers a safe and effective pharmacological adjunct to traditional hemostatic measures, helping to mitigate these risks
Understanding appropriate dosing strategies is critical for optimizing its benefits while minimizing potential adverse effects, making it a vital topic for surgical residents preparing for DNB and NEET SS examinations.
Indications
General Indications:
Tranexamic acid is indicated in surgical procedures where significant blood loss is anticipated or has occurred
This includes a wide range of specialties such as orthopedic surgery (joint replacements), cardiac surgery (CABG, valve replacement), obstetric and gynecological surgery (postpartum hemorrhage, hysterectomy), major abdominal and thoracic procedures, and trauma surgery
It is also used in certain elective surgeries known for high blood loss
It is not a substitute for meticulous surgical technique or blood component therapy when indicated.
Specific Surgical Contexts:
Orthopedic surgery: commonly used for total hip and knee arthroplasty to reduce postoperative blood loss and transfusion requirements
Cardiac surgery: employed to decrease mediastinal bleeding after cardiopulmonary bypass
Obstetric surgery: vital in managing postpartum hemorrhage and bleeding during cesarean sections
Spinal surgery: used to minimize intraoperative and postoperative bleeding
Major oncological resections: can help manage expected blood loss from vascular or complex tumor dissections.
Contraindications:
Absolute contraindications include active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, stroke), acquired or hereditary visual field defects or color vision disturbances, and known hypersensitivity to tranexamic acid
Relative contraindications include conditions predisposing to thrombosis, such as atrial fibrillation, and severe renal impairment
Caution is advised in patients with a history of seizures or those receiving certain medications.
Pharmacology And Mechanism
Mechanism Of Action:
Tranexamic acid functions as a competitive inhibitor of the enzyme plasminogen activator
By binding to lysine binding sites on plasminogen, it prevents plasminogen from binding to fibrin and being converted to plasmin
Plasmin is the enzyme responsible for degrading fibrin, the structural protein of blood clots
Thus, TXA stabilizes existing clots and prevents their premature lysis, thereby reducing blood loss
Its action is reversible and dose-dependent.
Pharmacokinetics:
TXA is rapidly absorbed after oral administration, with peak plasma concentrations reached within 2-4 hours
Intravenous administration results in immediate high plasma levels
It has a relatively short half-life of approximately 2-3 hours and is primarily excreted unchanged by the kidneys
Dosage adjustments are necessary in patients with renal insufficiency to prevent accumulation and potential toxicity
It does not significantly bind to plasma proteins and has limited tissue distribution.
Drug Interactions:
Concurrent use with prothrombotic agents (e.g., oral contraceptives, Factor VIIa) may increase the risk of thrombosis
Concomitant administration with fibrinolytic agents (e.g., streptokinase, alteplase) may antagonize their effects
Combination with oral contraceptives may increase the risk of venous thromboembolism
Caution should be exercised when TXA is used in patients receiving hormonal therapy or other agents affecting hemostasis.
Dosing Protocols In Surgery
Orthopedic Surgery:
For total hip or knee arthroplasty, a common IV regimen is a loading dose of 10 mg/kg administered over 10-20 minutes prior to incision, followed by an infusion of 1 mg/kg/hour for the duration of the surgery
Alternatively, oral regimens like 1 gram three times daily for 3 days, starting 2-4 hours before surgery, are also effective
Some protocols involve multiple IV doses postoperatively.
Cardiac Surgery:
For adult cardiac surgery, a typical IV regimen involves a loading dose of 100 mg/kg (or 1-5 g) administered as a bolus over 15-30 minutes before incision, followed by a continuous infusion of 10-25 mg/kg/hour throughout cardiopulmonary bypass
Some protocols omit the intraoperative infusion and use higher initial doses
Pediatric cardiac surgery protocols may vary significantly and require weight-based adjustments.
Obstetric And Gynecological Surgery:
For postpartum hemorrhage, the WHO recommends 1 gram of TXA intravenously as soon as possible after birth
If bleeding continues, a second dose of 1 gram can be given after 30 minutes
For cesarean sections, similar doses can be administered prophylactically or therapeutically
For gynecological procedures, 10-15 mg/kg IV before surgery and every 6-8 hours postoperatively may be used, though evidence is less robust than for obstetric hemorrhage.
Other Surgical Procedures:
For general major surgeries with expected blood loss, a common protocol is 10 mg/kg IV over 30 minutes prior to incision, with a potential repeat dose if bleeding persists or if reoperation is required
Trauma patients may receive 1 gram IV as an initial bolus, followed by 1 gram over 8 hours
Dosing should be individualized based on patient factors, surgical complexity, and institutional guidelines
Dose reduction is essential in patients with renal impairment.
Monitoring And Adverse Effects
Monitoring Parameters:
Patients receiving TXA should be monitored for signs of excessive bleeding, as well as for potential thrombotic events
Vital signs, urine output, and operative blood loss should be closely observed
Laboratory tests may include complete blood count, coagulation profile (PT, aPTT, fibrinogen), and D-dimer if indicated
Postoperative neurological status is also important, especially in patients with a history of seizures or stroke.
Common Adverse Effects:
The most frequently reported side effects are gastrointestinal disturbances, such as nausea, vomiting, and diarrhea
Hypersensitivity reactions are rare but can occur
Other reported effects include headache, dizziness, and visual disturbances
Hypertension can occur, particularly with rapid IV administration.
Rare But Serious Adverse Effects:
The most serious potential adverse effect is thromboembolism, including deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accidents (CVA)
These risks are generally low, especially when TXA is used appropriately and contraindications are observed
However, caution is warranted in patients with risk factors for thrombosis
Seizures have been reported, particularly with very high doses, and are more likely in individuals with a history of epilepsy.
Key Points
Exam Focus:
Understand the mechanism of action of TXA as an antifibrinolytic
Memorize the typical loading and maintenance doses for common surgical specialties (orthopedic, cardiac, obstetric)
Know the contraindications, especially active thromboembolic disease
Recognize the signs and symptoms of potential adverse effects, particularly thromboembolism.
Clinical Pearls:
Always consider renal function when dosing TXA
dose reduction is crucial in renal impairment
TXA is not a substitute for meticulous surgical technique or appropriate blood product management
Document TXA administration carefully, including dose, route, and timing
Be aware of institutional protocols and updated guidelines for TXA use.
Common Mistakes:
Administering TXA without considering contraindications, especially a history of DVT/PE or stroke
Using standard adult doses in pediatric patients without appropriate adjustments
Failure to reduce the dose in patients with impaired renal function, leading to potential toxicity
Over-reliance on TXA and neglecting standard surgical hemostatic techniques
Not recognizing or managing potential thrombotic complications promptly.