Tranexamic Acid Use in Orthopaedic Surgery

Preoperative Assessment for TXA Use

Preoperative Laboratory Assessment

Renal Function and Dose Adjustment

Risk Stratification and Contraindication Assessment

Thrombophilia Screening

Question: Should patients be screened for thrombophilia before TXA?

Answer: No routine thrombophilia screening is recommended.

Rationale:

• Meta-analyses show no increased VTE risk with TXA at therapeutic doses
• Thrombophilia testing is expensive and rarely changes management
• Patients with known thrombophilia can still receive TXA with appropriate VTE prophylaxis
• Individual risk-benefit discussion if severe hereditary thrombophilia

Intraoperative Monitoring

Postoperative Investigations

Routine postoperative testing for TXA:

• Standard full blood count (Day 1) - assess for bleeding/anemia
• No specific TXA-related testing required
• Coagulation studies NOT routinely indicated

Investigation for suspected adverse events:

TXA Dosing Protocols by Procedure

Route Selection

Decision Algorithm for TXA Administration

Confirm eligibility:

• Check renal function (eGFR)
• Review contraindications (active VTE, seizure history)
• Standard preoperative workup complete
• Document TXA plan in operative consent

Choose route:

• Standard patient: IV or topical (equivalent efficacy)
• Renal impairment: Topical preferred, or reduced IV dose
• Seizure history: Topical preferred
• Patient preference: Either route acceptable

Optimize timing:

• IV bolus: 10-15 minutes before skin incision
• Topical: Applied at end of procedure before closure
• Combined: IV pre-incision + topical at closure (no added benefit in most studies)

Consider repeat dose if:

• Procedure over 3 hours (TXA half-life 2-3 hours)
• Ongoing significant blood loss
• Revision surgery or complex reconstruction
• Dose: Half the initial dose, or full dose at 3 hours

VTE Prophylaxis Considerations

Evidence-Based Dosing Strategies

Special Population Management

High-Risk Patients:

Trauma-Specific Management (CRASH-2 Protocol)

Oral TXA Administration

Emerging evidence for oral route:

Oral protocol: 2g oral TXA 2 hours preoperatively is an emerging cost-effective alternative.

Management of Bleeding Despite TXA

If excessive bleeding persists after TXA administration:

• Verify timing (pre-incision)

  • Confirm adequate dose (15-20mg/kg)
  • Consider repeat dose if greater than 3 hours elapsed

• Meticulous surgical technique

  • Electrocautery, bone wax, topical hemostatics
  • Direct pressure, drain placement

• Check point-of-care hemoglobin

  • Transfuse if indicated (Hb less than 70-80 g/L)
  • Consider FFP/platelets if coagulopathic
  • Correct hypothermia and acidosis

• Additional TXA (up to 3g total) if ongoing fibrinolysis

  • Aprotinin historically used but withdrawn (renal toxicity)
  • Aminocaproic acid (alternative antifibrinolytic)

TXA Administration Techniques

Step-by-Step IV TXA Administration

Before induction:

• Confirm TXA dose with anesthetist
• Standard: 15-20mg/kg or 1-2g flat dose
• Prepare in 100mL normal saline
• Label syringe/bag clearly

Optimal timing:

• Start infusion after induction, before incision
• Complete bolus 10-15 minutes before skin incision
• Allows therapeutic plasma level at time of surgical trauma

Infusion technique:

• Give as slow IV infusion over 10 minutes (not rapid push)
• Rapid administration can cause transient hypotension
• Can be given via peripheral or central IV access

Record keeping:

• Document dose, timing, and route in anesthetic chart
• Include in operative note
• Note any adverse reactions

Step-by-Step Topical TXA Application

Preparation:

• Draw up 2-3g TXA (2-3 x 1g ampoules)
• Dilute in 50-100mL normal saline
• Prepare in sterile bowl or syringe
• Label clearly on surgical field

Before application:

• Complete bone cuts, soft tissue release
• Achieve mechanical hemostasis (cautery, bone wax)
• Control obvious bleeding points
• TXA augments but does not replace surgical hemostasis

In TKA/THA:

• Instill solution into joint cavity
• Ensure contact with all bleeding surfaces
• Some surgeons soak gauze and pack wound
• Close capsule/fascia over solution

Maintain contact:

• 5-10 minute dwell time optimal
• If drain used, clamp drain during dwell period
• Unclamp drain after dwell time
• Some protocols: instill via drain tube postoperatively

Procedure-Specific Considerations

Technical Considerations for Topical Application

Joint-specific techniques:

Drain management with topical TXA:

Combined IV and Topical Administration

Rationale for combined approach:

• IV provides systemic antifibrinolytic effect
• Topical provides high local concentration at bleeding surface
• Theoretical synergy, though evidence shows marginal benefit

Protocol:

1. IV TXA 15-20mg/kg pre-incision
2. Topical TXA 2-3g at wound closure
3. Consider if high blood loss expected (revision, complex primary)

Evidence:

• Multiple RCTs comparing combined vs single route
• Most show no significant additional benefit from combined approach
• Combined approach safe but adds cost without clear benefit in routine cases

Tourniquet and TXA Interaction (TKA)

Effect of tourniquet on TXA efficacy:

Key point: TXA timing is PRE-INCISION regardless of tourniquet strategy.

Intraoperative Bleeding Assessment

When to give additional TXA intraoperatively:

Postoperative TXA Administration

Postoperative dosing protocols:

Some centers use postoperative TXA dosing:

• 1g IV at 3 hours postoperatively
• Additional 1g at 6 hours (rarely used)

Evidence:

• Limited additional benefit in most studies
• May be useful if ongoing oozing or concern for late fibrinolysis
• Standard practice does not routinely include postoperative doses

Technical Pearls

IV Administration:

• Slow infusion prevents hypotension (give over 10 min, not bolus)
• Compatible with most IV fluids
• Can be mixed with other anesthetic agents (check compatibility)

Topical Application:

• Solution can be warmed to body temperature (no evidence benefit)
• Can soak absorbable gelatin sponge in TXA for additional effect
• Avoid mixing with blood products or other medications
• Some surgeons spray solution with atomizer for even distribution

Overview of TXA Safety

Thromboembolic Complications

Seizure Risk

Mechanism of TXA-related seizures:

• TXA is a GABA-A receptor antagonist at high concentrations
• High plasma levels (over 80-100 µg/mL) can lower seizure threshold
• Occurs mainly with doses over 100mg/kg (cardiac surgery) or renal impairment
• Orthopaedic doses rarely achieve these levels

Gastrointestinal Effects

Common but minor:

• Nausea and vomiting (under 10%)
• Diarrhea (less than 5%)
• Usually self-limiting
• Does not require discontinuation

Hypotension

With IV administration:

• Transient hypotension if given as rapid IV push
• Prevention: Slow infusion over 10 minutes
• Rarely clinically significant
• Monitor blood pressure during administration

Detailed Thromboembolic Safety Analysis

CRASH-2 Trial Vascular Events:

Conclusion: No signal for increased thromboembolic events with TXA use.

Total Joint Arthroplasty Meta-Analysis Data:

• Combined analysis of over 15,000 patients from RCTs
• VTE rate: 0.6% TXA vs 0.8% control (non-significant)
• Symptomatic DVT: 0.3% both groups
• PE: 0.2% both groups

Seizure Risk: Detailed Analysis

Cardiac Surgery Experience:

• Higher doses used (50-150 mg/kg)
• Seizure incidence up to 3-7% at very high doses
• Led to dose reduction recommendations in cardiac surgery

Orthopaedic Surgery:

• Standard doses (15-20mg/kg) rarely cause seizures
• Case reports exist but extremely rare
• Risk increases with:
  • Renal impairment (reduced clearance)
  • Open blood-brain barrier (trauma, intracranial surgery)
  • History of seizure disorder

Rare Complications

Visual Disturbance:

• Extremely rare retinal toxicity with prolonged use
• Case reports with long-term oral TXA (menorrhagia treatment)
• Not reported with short-term perioperative use
• Mechanism: Possible retinal venous thrombosis

Allergic Reactions:

• Hypersensitivity reactions very rare
• Anaphylaxis not reported at standard doses
• Skin reactions (rash, urticaria) reported rarely

Drug Interactions

Complications in Special Populations

Renal Impairment:

• TXA 90% renally excreted
• Half-life prolonged (4-8 hours vs 2-3 hours)
• Higher plasma levels increase seizure risk
• Management: Reduce dose by 50% if eGFR 10-30, avoid if eGFR less than 10

Pregnancy:

• Limited safety data
• CRASH-2 included pregnant women (no specific adverse events)
• Use only if benefit clearly outweighs risk
• Not recommended for routine obstetric use (controversial)

History of VTE:

• Recent VTE (within 6 months): Relative contraindication
• Remote VTE (over 6 months): Usually safe with enhanced prophylaxis
• Active VTE: Absolute contraindication

Postoperative Monitoring After TXA

VTE Prophylaxis

Blood Transfusion Considerations

TXA reduces but does not eliminate transfusion need:

• Transfusion rate with TXA: 2-5% (vs 15-25% without)
• Use same transfusion thresholds as for any surgery
• Restrictive transfusion strategy (Hb greater than 70 g/L) appropriate

Wound Care

Standard wound care applies:

• Keep wound dry for 24-48 hours
• Monitor for hematoma, swelling, drainage
• TXA typically REDUCES wound complications by reducing hematoma

If excessive drainage or hematoma:

• TXA effect has worn off (half-life 2-3 hours)
• Additional TXA NOT usually indicated postoperatively
• Assess for surgical bleeding requiring return to theatre

Rehabilitation

TXA does not affect rehabilitation:

• Early mobilization as per standard protocol
• Weight-bearing as tolerated (or as per surgical plan)
• Physiotherapy begins Day 0 or Day 1
• No TXA-specific activity restrictions

Postoperative TXA Dosing Protocols

Some centers use postoperative TXA:

Recommendation: Routine postoperative TXA dosing is NOT required. Consider only if ongoing oozing or concern for hyperfibrinolysis.

Managing Ongoing Bleeding

If postoperative bleeding is excessive:

Criteria for concern:

• Drain output over 500mL in first 4 hours
• Visible wound hematoma expanding
• Hemoglobin drop greater than 30 g/L
• Hemodynamic instability

Conservative measures:

• Compression dressing, ice
• Reverse anticoagulation if excessive
• Consider additional TXA dose (1g IV) if within 6 hours of surgery
• Transfuse if indicated

Indications for return to theatre:

• Expanding hematoma compromising wound
• Hemodynamic instability despite resuscitation
• Drain output greater than 1500mL in 6-8 hours
• Suspected arterial bleeding

Drain Management Protocols

Options after topical TXA:

Trend: Many surgeons are moving to drainless protocols with TXA, as blood loss reduction makes drains less necessary.

Enhanced Recovery (ERAS) Integration

TXA is a core component of ERAS protocols:

Postoperative Complications Potentially Affected by TXA

Complications REDUCED by TXA:

• Transfusion requirements (50-70% reduction)
• Wound hematoma
• Reoperation for bleeding

Complications NOT increased by TXA:

• Deep vein thrombosis
• Pulmonary embolism
• Wound infection
• Periprosthetic joint infection

Complications with uncertain relationship:

• Seizures: Only at very high doses or renal impairment
• Retinal toxicity: Not reported with short-term use

Primary Outcomes: Blood Loss Reduction

Key Outcome Metrics

Safety Outcomes

No increase in adverse events:

• DVT rate: No difference (0.2-0.3% both groups)
• PE rate: No difference (0.2-0.4% both groups)
• Stroke/MI: No difference
• Wound infection: No difference or slight reduction
• Seizures: Extremely rare at therapeutic doses

Cost-Effectiveness

TXA is one of the most cost-effective interventions in orthopaedic surgery.

Landmark Trial Evidence

CRASH-2 Trial (2010):

Key findings:

• 1.5% absolute mortality reduction
• NNT = 67 to save one life
• Timing critical: Benefit only if given within 3 hours

Meta-Analysis Data: Total Joint Arthroplasty

Cochrane Review (2016, updated 2020):

• 129 RCTs, over 10,000 patients
• Blood loss: SMD -0.92 (significantly reduced)
• Transfusion: RR 0.31 (69% relative reduction)
• VTE: RR 0.88 (non-significant reduction)
• Mortality: Too few events to analyze

Australian Registry-Level Data:

• TXA standard of care in most Australian TJA centers
• No signal for increased VTE in registry analysis
• Transfusion rates nationally reduced since TXA adoption

Route Comparison Outcomes

Conclusion: No clinically significant difference between routes. Choose based on patient factors and surgeon preference.

Subspecialty-Specific Outcomes

Trauma Surgery (CRASH-2):

• Mortality reduction: 1.5% absolute
• NNT = 67 to save one life
• Critical: Must be given within 3 hours

Spine Surgery:

• Blood loss reduction: 20-40%
• Less consistent than TJA (more heterogeneous procedures)
• Particularly beneficial in multilevel fusions and deformity correction

Shoulder Arthroplasty:

• Limited evidence (fewer RCTs)
• Consistent with TJA findings (blood loss reduction)
• Topical application feasible

Long-Term Outcomes

No evidence of long-term adverse effects:

• Registry follow-up shows no delayed VTE signal
• No increased implant failure or revision rates
• No delayed wound complications

Outcomes in High-Risk Populations

Future Directions

Emerging research:

• Oral TXA protocols (cost savings, equivalent efficacy)
• TXA in unicompartmental knee arthroplasty
• TXA in arthroscopic surgery
• Optimal dosing protocols (personalized medicine)
• TXA in pediatric orthopaedics

Total Knee Arthroplasty (TKA)

Key studies and meta-analyses:

• Multiple meta-analyses including over 10,000 patients demonstrate consistent 30-50% reduction in blood loss
• Reduction in transfusion rates from approximately 20% to under 5% in most series
• No increase in symptomatic VTE or other thromboembolic complications

Route comparison:

• Intravenous: 15-20mg/kg bolus pre-incision, with or without repeat dose
• Topical: 2-3g in 50-100mL saline, 5-10 minute dwell time intra-articularly
• Combined: IV plus topical shows no additional benefit in most studies
• Oral: 1-2g pre-operatively, emerging evidence suggests similar efficacy

Outcomes:

• Mean blood loss reduction: 300-500mL
• Transfusion rate reduction: absolute risk reduction 15-20%
• No difference in infection, wound complications, or thrombosis
• Cost savings: approximately 300-500 dollars per patient from reduced transfusions

Total Hip Arthroplasty (THA)

Similar evidence profile to TKA:

• 30-40% reduction in blood loss across approaches (posterior, lateral, anterior)
• Reduced transfusion rates from 15-25% to under 10%
• Safe in both cemented and uncemented techniques
• Effective in revision surgery with higher doses considered

Dosing in THA:

• Standard: 1.5-2g IV bolus or 15-20mg/kg
• Topical: 2-3g in wound before closure
• Consider repeat dosing for prolonged procedures

The evidence demonstrates consistent benefit across all approaches to THA.

CRASH-2 Trial - Landmark Evidence

Study design:

• 20,211 trauma patients with significant bleeding
• Randomized to TXA vs placebo
• Protocol: 1g IV over 10 minutes, then 1g over 8 hours
• Initiated within 8 hours of injury (stratified by time)

Key findings:

• All-cause mortality: Reduced from 16.0% to 14.5% (absolute reduction 1.5%, RR 0.91)
• Death due to bleeding: Reduced from 5.7% to 4.9%
• Timing critical: Benefit when given within 3 hours. Harm if given after 3 hours (increased mortality)
• No increase in vascular occlusive events: DVT, PE, stroke, MI rates similar

CRASH-3 Trial - Traumatic Brain Injury

Extended TXA use to isolated or predominant TBI:

• Reduced head injury-related death in patients with mild-moderate TBI
• Same dosing protocol as CRASH-2
• Time window critical (within 3h)

Application in orthopaedic trauma:

• Pelvic fractures: Multiple studies show reduced transfusion requirements
• Femur fractures: Decreased blood loss and transfusion rates
• Acetabular fractures: Reduced perioperative bleeding
• Spine trauma: Beneficial in thoracolumbar fractures requiring surgery

Recommended protocol for trauma:

• Loading dose: 1g IV over 10 minutes
• Maintenance: 1g IV over 8 hours
• Timing: As soon as possible, ideally within 1 hour, certainly within 3 hours
• Contraindication: More than 3 hours post-injury (based on CRASH-2 subgroup analysis)

This conclusion establishes the time-critical nature of TXA in trauma.

Evidence in spinal procedures:

Deformity surgery:

• Meta-analyses show 30-40% reduction in blood loss in scoliosis and kyphosis correction
• Reduced transfusion requirements in multi-level instrumented fusions
• Particularly beneficial in posterior spinal fusion with extensive exposure

Dosing protocols:

• Loading dose: 10-15mg/kg over 15-20 minutes before incision
• Maintenance infusion: 1-2mg/kg/hour continued throughout procedure
• Alternative: Bolus dosing (10-15mg/kg repeated every 3-4 hours)

Safety in spine surgery:

• No increase in spinal epidural hematoma
• No difference in neurological complications
• Safe with intraoperative neuromonitoring (does not affect MEP/SSEP)

Special considerations:

• Revision surgery: Higher doses may be considered given greater blood loss risk
• Combined anterior-posterior: Continue infusion throughout staged procedures
• Minimally invasive: Still beneficial despite reduced exposure

The evidence supports routine use in major spine surgery with continuous infusion protocols preferred.

Fracture fixation:

• Hip fractures: Multiple RCTs show benefit in both intra- and extra-capsular fractures
• Periarticular fractures: Reduced blood loss in tibial plateau, pilon, distal femur fixation
• Long bone fractures: Decreased transfusion rates

Revision arthroplasty:

• Similar or greater benefit compared to primary surgery
• Consider higher doses (20-25mg/kg or 2-3g)
• Can combine IV and topical routes

Shoulder arthroplasty:

• Emerging evidence for benefit in anatomic and reverse total shoulder
• Dosing similar to THA (1.5-2g IV)

Foot and ankle surgery:

• Limited evidence but case series suggest benefit in hindfoot fusions and total ankle arthroplasty
• Lower doses sufficient (1g IV)

Tumor surgery:

• Beneficial in resection of vascular bone tumors
• Caution with extensive soft tissue dissection
• Individualize based on bleeding risk

These applications demonstrate versatility across orthopaedic practice.

Regulatory status:

• TGA approval: Tranexamic acid (Cyklokapron and generics) approved for reduction of perioperative blood loss
• PBS listing: Available on PBS for general prescribing
  • Cyklokapron 500mg tablets (authority required for some indications)
  • Cyklokapron injection 100mg/mL 5mL and 10mL ampoules
• Schedule: Schedule 4 (Prescription Only Medicine)

Hospital formulary:

Most Australian hospitals stock TXA in both tablet and injectable forms:

• Standard inclusion in surgical pharmacy protocols
• Often part of pre-printed order sets for arthroplasty and trauma
• Automatic dispensing for eligible procedures in some institutions

AOANJRR data:

The Australian Orthopaedic Association National Joint Replacement Registry does not specifically track TXA use, but transfusion rates have declined over the past decade:

• TKA transfusion rates: Decreased from approximately 20% to under 10% nationally
• THA transfusion rates: Decreased from 15-20% to under 10%
• This reduction correlates with increased TXA adoption and patient blood management programs

Blood supply context:

• Australian Red Cross Lifeblood manages national blood supply
• Donor-dependent system with finite supply
• Patient blood management (PBM) programs national priority
• TXA key component of PBM in elective orthopaedic surgery

National guidelines and initiatives:

National Blood Authority (NBA) Patient Blood Management Guidelines:

• Module 2 (Perioperative): Recommends TXA for elective surgery
• Supports routine use in joint arthroplasty and spine surgery
• Part of multimodal blood conservation strategy

Australian and New Zealand Society of Blood Transfusion (ANZSBT):

• Endorses TXA as part of PBM protocols
• Educational initiatives to increase appropriate use
• Monitoring of transfusion rates as quality indicator

State-based programs:

Several states have PBM coordinators and programs:

• Victoria: Safer Care Victoria PBM program
• NSW: Clinical Excellence Commission PBM initiatives
• Queensland: Queensland Health PBM framework
• All emphasize TXA use in elective orthopaedic surgery

Clinical practice variation:

Despite strong evidence and guidelines, TXA adoption varies:

• High-volume public hospitals: Often have protocols, high utilization
• Private hospitals: Variable, surgeon-dependent
• Regional centers: Increasing adoption with education and protocol development
• Trauma centers: CRASH-2 protocol increasingly standard in major trauma

Barriers to universal adoption:

• Knowledge gaps among some clinicians
• Perceived safety concerns (VTE risk, now refuted)
• Lack of standardized protocols in some institutions
• Cost concerns (misperception, given TXA is cost-saving)

Strategies to improve uptake:

• Integration into surgical checklists
• Pre-printed order sets with TXA as default for eligible procedures
• Pharmacy-driven initiatives and automatic dispensing
• Audit and feedback on transfusion rates and TXA utilization
• Educational programs for surgeons, anesthetists, and nursing staff

Future directions:

• National benchmarking of TXA use in arthroplasty and trauma
• AOANJRR potential expansion to capture PBM interventions
• Integration with other blood conservation techniques (cell salvage, restrictive transfusion)
• Research into optimal protocols for specific patient populations

This Australian context establishes TXA as a key component of national patient blood management strategies.