Tranexemic Acid

Disclaimer: This information is intended for educational purposes and should not be considered medical advice. It is crucial for clinicians to exercise their independent medical judgment and consider individual patient circumstances, local guidelines, and the latest evidence when making patient care decisions. The information provided is subject to change as new research emerges. Always consult official drug prescribing information and clinical guidelines before prescribing or administering any medication.

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 dissolution of fibrin clots and promoting hemostasis.
• Epidemiology: TXA is widely used globally in various clinical settings where excessive bleeding is a concern. Its utility spans from trauma and surgery to obstetric hemorrhage, gastrointestinal bleeding, and inherited bleeding disorders. The prevalence of conditions warranting TXA use, such as trauma, postpartum hemorrhage (PPH), and surgical bleeding, is high, making TXA a frequently administered medication.
• Classification: TXA is classified as an antifibrinolytic agent. It does not have further common subtypes.

Pathophysiology

• Mechanism: TXA acts by reversibly binding to the lysine binding sites on plasminogen and plasmin. These sites are essential for plasminogen binding to fibrin, which is a prerequisite for its activation to plasmin by tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA). By occupying these sites, TXA prevents plasminogen from binding to and being activated on the fibrin surface, thus inhibiting fibrinolysis (clot breakdown). This stabilizes the fibrin clot and reduces bleeding. TXA also directly inhibits plasmin, albeit to a lesser extent, further contributing to its antifibrinolytic effect.
• Risk Factors (for bleeding, warranting TXA consideration):
  • Trauma: Especially severe blunt or penetrating trauma with signs of hemorrhagic shock.
  • Surgery: Procedures associated with high blood loss (e.g., cardiac surgery, orthopedic surgery like total joint arthroplasty, spinal surgery, liver transplantation).
  • Obstetrics: Postpartum hemorrhage (PPH), peripartum hysterectomy.
  • Gastrointestinal Bleeding: Upper or lower GI bleeding, particularly non-variceal.
  • Hematologic Disorders: Hemophilia (adjunct to factor replacement), von Willebrand disease, menorrhagia, thrombocytopenia.
  • Local Fibrinolysis: Epistaxis, dental extractions in patients with bleeding disorders, uterine bleeding (e.g., abnormal uterine bleeding).
• Protective Factors (against excessive bleeding, where TXA might be beneficial): Not directly protective factors against bleeding, but rather conditions where TXA can enhance hemostasis:
  • Normal coagulation cascade components (fibrinogen, platelets, clotting factors).
  • Timely administration of TXA in acute bleeding scenarios.
  • Absence of severe coagulopathy that TXA alone cannot address (e.g., severe factor deficiencies requiring replacement).

Clinical Presentation (Indications for TXA)

TXA is not used to diagnose a condition but rather to treat or prevent bleeding in specific clinical scenarios. The signs and symptoms below refer to the clinical situations where TXA might be indicated.

Signs and Symptoms (of active bleeding)

• Cardinal Features:
  • Visible external hemorrhage (e.g., lacerations, epistaxis, vaginal bleeding).
  • Signs of internal bleeding (e.g., abdominal distension, hematoma formation, ecchymosis).
  • Hemodynamic instability: Tachycardia, hypotension, cool extremities, altered mental status (indicating hypovolemic shock).
  • Laboratory evidence of acute blood loss: Decreasing hemoglobin and hematocrit.
• Early Signs:
  • Increased heart rate, mild hypotension.
  • Pallor.
  • Excessive bleeding from wounds, surgical sites, or mucosal surfaces.
  • Abnormal uterine bleeding, menorrhagia (often reported as subjective heavy flow).
• Advanced Signs:
  • Profound hypotension, severe tachycardia.
  • Altered consciousness, confusion, unresponsiveness.
  • Anuria/oliguria.
  • Lactic acidosis, disseminated intravascular coagulation (DIC).
• Atypical Presentations:
  • Occult bleeding leading to insidious anemia.
  • Delayed re-bleeding after initial hemostasis.
  • Bleeding in anatomically constrained spaces (e.g., retroperitoneal, intracranial) where signs may be delayed or nonspecific.

Physical Examination (Assessment of bleeding)

• Inspection:
  • Observe for active external bleeding, amount, and rate.
  • Note skin color (pallor, cyanosis).
  • Assess level of consciousness.
  • Inspect surgical sites, trauma wounds, genitourinary/gastrointestinal orifices for bleeding.
  • Assess for abdominal distension or signs of peritonitis (suggesting intra-abdominal hemorrhage).
• Palpation:
  • Assess peripheral pulses for rate and quality.
  • Palpate skin for temperature and moisture (cool, clammy in shock).
  • Palpate abdomen for tenderness, guarding, or masses.
  • Assess for palpable hematomas.
• Special Tests:
  • Vitals Signs: Repeated monitoring of blood pressure, heart rate, respiratory rate, and oxygen saturation.
  • Focused Assessment with Sonography for Trauma (FAST) exam: In trauma, to detect free fluid (blood) in the abdomen or pericardium.
  • Tourniquet test: Rarely used, but can assess capillary fragility.

Diagnostic Approach (Assessment for TXA indication)

The diagnostic approach focuses on confirming active bleeding, assessing its severity, identifying its source, and evaluating coagulation status to determine if TXA is appropriate.

History Taking

• Key Questions:
  • Onset, duration, and estimated quantity of bleeding.
  • Nature of bleeding (e.g., bright red, dark, clots, intermittent, continuous).
  • Mechanism of injury (if traumatic).
  • Recent surgeries or procedures.
  • History of bleeding disorders (personal or family).
  • Current medications (especially anticoagulants, antiplatelets, NSAIDs, hormonal therapy).
  • Past medical history (liver disease, kidney disease, malignancy, cardiovascular disease, thrombotic events).
  • In women: Menstrual history, pregnancy status, recent delivery.
  • Symptoms of hypovolemia (dizziness, syncope, weakness, thirst).
• Red Flags:
  • Rapidly increasing bleeding.
  • Signs of hemodynamic instability (syncope, severe dizziness, chest pain, shortness of breath).
  • Altered mental status.
  • Bleeding despite direct pressure or standard hemostatic measures.
  • History of severe liver disease or known coagulopathy.
  • Suspected intracranial hemorrhage (caution with TXA).

Laboratory Tests

• First-Line:
  • Complete Blood Count (CBC): Hemoglobin, hematocrit (to assess acute blood loss and baseline), platelet count.
  • Coagulation Panel: Prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) (to assess for underlying coagulopathy).
  • Fibrinogen level: Important for assessing clot quality and guiding replacement, especially in massive hemorrhage.
  • Type and Cross-Match: For potential blood transfusions.
  • Renal function tests (Creatinine, BUN): To guide TXA dosing in renal impairment.
  • Liver function tests: To assess for underlying liver disease that can affect coagulation.
• Confirmatory (for specific causes of bleeding or monitoring TXA effect):
  • Thromboelastography (TEG) or Rotational Thromboelastometry (ROTEM): Point-of-care tests that provide a global assessment of clot formation, strength, and lysis. Can identify hyperfibrinolysis that may benefit from TXA.
  • D-dimer: Elevated levels can suggest ongoing fibrinolysis, but are also elevated in many other conditions (e.g., thrombosis, inflammation).
• Monitoring:
  • Repeat CBC, coagulation panel as needed based on bleeding severity and interventions.
  • Repeat fibrinogen levels.
  • TEG/ROTEM if available and initial results showed hyperfibrinolysis.

Imaging

• Recommended (to identify source of bleeding):
  • Ultrasound: FAST exam in trauma; transvaginal/abdominal ultrasound for obstetric hemorrhage; Doppler ultrasound for vascular injury.
  • Computed Tomography (CT) scan:
    • CT Angiography (CTA): To identify vascular injury or active extravasation in trauma, GI bleeding, or other sources.
    • CT Abdomen/Pelvis: For internal hemorrhage.
    • CT Head: For intracranial hemorrhage (though TXA's role here is complex and debated, and its use is controversial).
• Advanced (for specific complex scenarios):
  • Angiography/Interventional Radiology: For embolization of bleeding vessels (e.g., in GI bleeding, pelvic fractures, post-partum hemorrhage).
  • Endoscopy (Upper/Lower GI): To visualize and treat source of GI bleeding.
  • MRI: Rarely for acute bleeding, but can define anatomical relationships.

Management (Tranexamic Acid Dosing and Indications)

Acute Management

General Principles: Early administration of TXA in acute severe bleeding is crucial, ideally within 3 hours of injury/onset. TXA is generally well-tolerated but requires careful dosing, especially in renal impairment.

• Trauma (CRASH-2 Trial):
  • Immediate: 1 gram IV over 10 minutes, initiated as soon as possible, ideally within 3 hours of injury.
  • Stabilization: Followed by an infusion of 1 gram IV over 8 hours.
  • Emergency: For patients with or at risk of significant hemorrhage.
  • Key Criterion: Administer when systolic blood pressure < 90 mmHg or heart rate > 110 bpm, or clinical evidence of significant bleeding. Not recommended after 3 hours if bleeding has stopped. If bleeding continues after 3 hours, consider repeating doses based on clinical judgment and local protocols, but this is off-label.
• Postpartum Hemorrhage (PPH) (WOMAN Trial):
  • Immediate: 1 gram IV over 10-20 minutes, administered as soon as possible after diagnosis of PPH (usually within 3 hours).
  • Stabilization: If bleeding continues after 30 minutes or stops and restarts within 24 hours of the first dose, a second dose of 1 gram IV may be given.
  • Emergency: For PPH that is unresponsive to uterotonics, or severe PPH.
  • Key Criterion: For PPH due to uterine atony or trauma, not routinely for placental retention.
• Gastrointestinal Bleeding (HALT-IT Trial):
  • Dose: 1 gram IV loading dose, followed by 3 grams IV over 24 hours, or 1 gram IV three times daily for up to 3 days.
  • Evidence: HALT-IT trial showed no mortality benefit for TXA in GI bleeding and a possible increase in thrombotic events. Therefore, routine use of TXA for acute GI bleeding is not currently recommended outside of clinical trials, except potentially in very specific circumstances where hyperfibrinolysis is proven (e.g., by TEG/ROTEM).
• Perioperative Bleeding (Elective Surgery):
  • Loading Dose: 10-15 mg/kg IV administered shortly before surgical incision.
  • Maintenance Infusion: 1-5 mg/kg/hour during surgery, or additional boluses as needed, typically up to a total dose of 100 mg/kg or 1 gram orally 3 times daily for 2-5 days postoperatively (for procedures like total joint replacement).
  • Specific Surgeries:
    • Cardiac Surgery: 10-30 mg/kg IV loading dose, followed by 10-15 mg/kg/hr infusion, or a high fixed dose (e.g., 1-2 grams IV) followed by infusion. Dosing varies by protocol (e.g., "high dose" for CABG).
    • Orthopedic (e.g., Total Knee/Hip Arthroplasty):
      • IV: 10-15 mg/kg or 1 gram IV pre-operatively, followed by 1 gram IV 3 hours later or a continuous infusion. Some protocols use a single 1 gram IV dose at incision.
      • Topical: 1-3 grams in 50-100 mL saline locally into the joint at closure.
      • Oral: 1-1.5 grams orally 2-3 hours pre-operatively, then 1-1.5 grams every 8 hours for 24-48 hours.
    • Spinal Surgery: 10 mg/kg IV loading, then 1 mg/kg/hour infusion.
• Abnormal Uterine Bleeding (AUB)/Menorrhagia:
  • Oral: 1.3 grams (two 650 mg tablets) orally three times daily for up to 5 days during menstruation. Maximum 3.9 grams/day.
  • IV (rarely): 10 mg/kg (up to 600 mg) IV 3-4 times daily for 3 days.
• Epistaxis:
  • Oral: 1-1.5 grams 2-3 times daily for 5-7 days.
  • Topical: Soaked gauze/packing or spray (e.g., 500 mg TXA powder mixed with 5 mL saline, or use of nasal spray with 10% TXA solution).
• Hemophilia/Bleeding Disorders (adjunct to factor replacement):
  • Oral: 10-25 mg/kg (typically 1-1.5 grams) 2-4 times daily.
  • IV: 10 mg/kg (max 1 gram) 2-4 times daily.
  • Used particularly for mucocutaneous bleeding, dental extractions, and menorrhagia. Not used for isolated urinary tract bleeding in hemophilia due to risk of clot in ureter/kidney.

Chronic Management

• Pharmacological:
  • For conditions like hereditary angioedema (HAE), TXA (oral) may be used chronically, though C1-esterase inhibitor concentrates are first-line. Dosing for HAE: 1-1.5 grams orally 2-3 times daily.
  • For menorrhagia, it's used episodically during menstruation.
• Non-pharmacological: Not applicable as TXA is a pharmacological agent.
• Monitoring:
  • Monitor for bleeding cessation or reduction.
  • Monitor for thrombotic complications, especially in patients with pre-existing risk factors.
  • Monitor renal function in prolonged use or in patients with impaired kidney function.
  • Consider ophthalmologic monitoring (e.g., slit-lamp exam, visual acuity, color vision) if used for prolonged periods (months to years), as retinal changes have been reported rarely.

Treatment Algorithms

• First-Line:
  • Trauma/PPH: Prompt administration (within 3 hours) in actively bleeding patients at risk of significant hemorrhage.
  • Surgical: Pre-operative or intra-operative administration in high-risk surgeries (e.g., cardiac, major orthopedic).
  • Menorrhagia: Often first-line oral therapy for heavy menstrual bleeding.
• Second-Line:
  • May be considered as adjunct to other hemostatic measures (e.g., factor replacement, interventional radiology) in refractory bleeding.
  • For non-variceal GI bleeding, TXA is generally not first-line and its routine use is not supported by recent evidence (HALT-IT).
• Refractory Cases:
  • If bleeding persists despite TXA, reassess for other causes (e.g., surgical bleeding, severe coagulopathy, severe factor deficiency, DIC).
  • Consider alternative or additional hemostatic agents (e.g., factor concentrates, prothrombin complex concentrate, desmopressin, recombinant factor VIIa), massive transfusion protocols, and surgical/interventional hemostasis.
  • In cases of suspected ongoing hyperfibrinolysis despite TXA, consider higher doses or repeat dosing based on TEG/ROTEM guided therapy, if available and appropriate, though evidence for this is limited.

Complications

• Common:
  • Nausea, vomiting, diarrhea (especially with oral formulations or rapid IV infusion).
  • Dizziness, headache.
  • Hypotension (with rapid IV infusion).
  • Allergic skin reactions (rash, pruritus).
• Serious:
  • Thrombotic events: Arterial and venous thrombosis (e.g., DVT, PE, MI, stroke). While TXA is antifibrinolytic, large clinical trials have generally shown the overall benefit of reducing bleeding mortality outweighs the risk of thrombosis in acute severe hemorrhage (e.g., CRASH-2, WOMAN). However, HALT-IT found a potential increase in thrombosis in GI bleeding. Risk is higher in patients with pre-existing thrombotic risk factors.
  • Seizures: Rare, but reported, particularly with high doses in cardiac surgery or renal impairment, likely due to competitive inhibition of GABA-A receptors.
  • Visual disturbances: Color vision impairment, retinal changes (rare, typically with long-term high-dose oral use).
  • Renal cortical necrosis: Extremely rare.
  • Ureteric obstruction: In patients with hematuria, may form clots within the renal pelvis or ureter, leading to obstruction. TXA is generally contraindicated for upper urinary tract bleeding.

Prognosis

• Factors:
  • Timeliness of administration: Earlier administration (within 3 hours of onset of bleeding) is associated with improved outcomes, especially in trauma and PPH.
  • Severity of underlying bleeding: Massive hemorrhage carries a poorer prognosis regardless of TXA.
  • Underlying comorbidities: Patients with severe liver disease, coagulopathy, or significant cardiovascular disease may have worse outcomes.
  • Appropriate patient selection: TXA is beneficial in hyperfibrinolytic states but less so or potentially harmful in other conditions (e.g., uncomplicated GI bleeding).
  • Concurrent management: Adequate resuscitation, identification and control of bleeding source, and correction of coagulopathy are critical.
• Survival:
  • Trauma (CRASH-2): Reduced all-cause mortality (RR 0.91, 95% CI 0.85-0.97) and death due to bleeding (RR 0.85, 95% CI 0.76-0.96) when administered within 3 hours.
  • PPH (WOMAN): Reduced death due to bleeding (RR 0.81, 95% CI 0.65-1.00) and hysterectomy (RR 0.64, 95% CI 0.49-0.85).
  • GI Bleeding (HALT-IT): No reduction in 28-day mortality, and a possible increase in thrombotic events.
• Quality of Life: By reducing blood transfusions and preventing complications of severe hemorrhage, TXA can indirectly improve quality of life and reduce hospital stay. In menorrhagia, it significantly reduces menstrual blood loss, improving quality of life.

Prevention

• Primary (Preventing initial occurrence of severe bleeding via TXA use):
  • Elective Surgery: Prophylactic administration of TXA pre-operatively or intra-operatively in surgeries known to have significant blood loss (e.g., total joint replacement, cardiac surgery) reduces the need for blood transfusions and overall blood loss.
  • Hereditary Angioedema: Regular oral TXA can prevent attacks in some patients.
• Secondary (Early detection and intervention to prevent complications of existing bleeding):
  • Trauma/PPH: Early administration of TXA to prevent progression to massive hemorrhage and death. This is the primary role of TXA in these acute settings.
  • Menorrhagia: Timely oral TXA during menstruation to prevent severe blood loss and iron deficiency anemia.
• Tertiary (Preventing complications of TXA use or prolonged bleeding):
  • Careful patient selection to avoid administering TXA in patients at very high risk of thrombosis without clear benefit.
  • Dose adjustment in renal impairment to prevent accumulation and reduce risk of adverse effects like seizures.
  • Avoidance in upper urinary tract bleeding where clot formation can cause obstruction.

Special Populations

• Pediatric:
  • Dosing: Generally 10-15 mg/kg IV or orally every 6-8 hours. Max 1 gram/dose or 100 mg/kg/day. Specific doses vary based on indication (e.g., cardiac surgery, trauma).
  • Indications: Similar to adults (e.g., trauma, surgery, bleeding disorders, menorrhagia in adolescents).
  • Caution: Limited data for some indications; risk-benefit should be carefully weighed.
• Geriatric:
  • Dosing: No specific geriatric dose adjustment is typically needed beyond renal function.
  • Caution: Elderly patients may have increased risk factors for thrombosis (e.g., atrial fibrillation, immobility, vascular disease), requiring careful assessment of the risk-benefit profile. Renal function decline is common and requires dose adjustment.
• Pregnancy:
  • PPH: Strongly recommended for the treatment of PPH (see Management section for dosing). The WOMAN trial confirmed its safety and efficacy in this setting.
  • Other indications: Use for other indications during pregnancy should be considered only if the potential benefit outweighs the potential risk. Generally considered Category B or C in pregnancy depending on source. Limited data on congenital anomalies.
• Comorbidities:
  • Renal Impairment: TXA is primarily eliminated unchanged by the kidneys. Dose adjustment is critical to prevent accumulation and adverse effects (e.g., seizures).
    • CrCl 50-80 mL/min: Reduce dose by 50%.
    • CrCl 10-50 mL/min: Reduce dose by 75%.
    • CrCl < 10 mL/min or ESRD: Reduce dose by 90% or consider 10 mg/kg every 24-48 hours. Hemodialysis removes TXA.
  • Thrombotic Risk: History of DVT/PE, arterial thrombosis (MI, stroke), known thrombophilia. Use with caution. The risk-benefit must be carefully assessed. In life-threatening hemorrhage, benefit usually outweighs risk.
  • Seizure Disorder: Use with extreme caution due to increased risk of seizures.
  • Disseminated Intravascular Coagulation (DIC): Can be considered if there is evidence of hyperfibrinolysis, but should not be used in isolation and is contraindicated if there is evidence of widespread microvascular thrombosis without significant bleeding.
  • Color Vision Defect: Patients should be monitored if long-term treatment is planned.

Clinical Pearls

• Diagnostic:
  • Think TXA early in acute severe bleeding (trauma, PPH), especially if within 3 hours of onset.
  • TEG/ROTEM can help identify hyperfibrinolysis and guide TXA administration, but are not universally available or required for initial empirical use in trauma/PPH.
• Treatment:
  • Timing is key: "The Golden Hour" for trauma, "The Platinum 3 Hours" for PPH.
  • Dosing accuracy: Ensure correct dosing based on indication and renal function. Rapid IV infusion can cause hypotension.
  • Not a substitute for definitive hemostasis: TXA reduces bleeding but does not fix the source of bleeding (e.g., surgical repair, uterine massage).
  • GI Bleeding Caution: Do NOT routinely use TXA for acute GI bleeding unless hyperfibrinolysis is strongly suspected/proven, or within specific trial protocols, given the HALT-IT trial findings.
  • Oral vs. IV: Oral TXA is effective for menorrhagia and some prophylactic uses; IV is for acute severe bleeding.
  • Contraindications: Active intravascular clotting (e.g., stroke, MI, DVT, PE), acquired defective color vision, subarachnoid hemorrhage (controversial due to seizure risk). Upper urinary tract bleeding due to clot obstruction risk.
• Pitfalls:
  • Delayed administration: Reduces efficacy significantly.
  • Overdosing in renal impairment: Leads to drug accumulation and increased risk of seizures.
  • Ignoring thrombotic risk: While beneficial for bleeding, always consider a patient's overall thrombotic risk profile.
  • Using TXA for every bleeding scenario: Not all bleeding benefits from TXA (e.g., many forms of GI bleeding, isolated upper urinary tract bleeding).
  • Assuming TXA fixes all coagulopathy: It only addresses fibrinolysis; other factors (e.g., severe factor deficiencies, severe thrombocytopenia) still need correction.

Recent Updates

• Guidelines:
  • World Health Organization (WHO): Strong recommendation for TXA in PPH (2017) and for trauma (2018), based on WOMAN and CRASH-2 trials respectively.
  • American College of Surgeons (ACS) Committee on Trauma (COT): Included TXA in their ATLS (Advanced Trauma Life Support) guidelines.
  • European Guidelines on Management of Major Bleeding and Coagulopathy Following Trauma: Recommend TXA within 3 hours.
• Evidence:
  • HALT-IT Trial (2020): Large randomized controlled trial on TXA in acute gastrointestinal bleeding (2019). Showed no significant reduction in mortality and a potential increase in thrombotic events (myocardial infarction and stroke). This has significantly shifted the recommendation against routine TXA use in unselected GI bleeders.
  • TACS Trial (2022): Ongoing trials exploring TXA in specific acute settings like traumatic brain injury.
• Controversies:
  • Intracranial Hemorrhage (ICH): While TXA is used in trauma with systemic bleeding, its role in isolated traumatic ICH and spontaneous ICH remains debated. Some studies show reduced hematoma expansion, but potential for increased thrombotic events and seizures are concerns. Current guidelines generally do not recommend routine use for spontaneous ICH.
  • Specific GI Bleeding Subtypes: Whether certain subtypes of GI bleeding (e.g., variceal bleeding with suspected hyperfibrinolysis) might still benefit from TXA. Current evidence remains unclear, and general recommendation is against routine use.
  • Repeat Dosing in Trauma: The CRASH-2 trial used a fixed 1g bolus then 1g infusion over 8 hours. The utility of repeat bolus dosing (beyond the initial 2g total) for ongoing massive hemorrhage is not well-established by large trials and should be done with caution.

Key References

• Guidelines:
  • World Health Organization (WHO) Guidelines for the management of postpartum haemorrhage and retained placenta. (2017).
  • World Health Organization (WHO) Guidelines on the management of trauma and emergency surgery care. (2018).
  • European Society of Anesthesiology (ESA) Guidelines for management of severe perioperative bleeding. (2017/2021 updates).
  • ATLS (Advanced Trauma Life Support) Student Course Manual. (Current Edition).
• Studies:
  • CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32.
  • WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 27;389(10084):2105-2116.
  • HALT-IT Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and transfusion requirement in patients with gastrointestinal bleeding: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jun 20;395(10241):1927-1939.
  • Roberts I, et al. Tranexamic acid for trauma--a systematic review and meta-analysis. Crit Care. 2014 Jan 20;18(1):R19.
• Reviews:
  • Ker K, et al. Tranexamic acid for trauma patients: A systematic review and meta-analysis of randomised controlled trials. PLoS One. 2013;8(5):e64095.
  • Franchini M, et al. Tranexamic acid for the treatment of bleeding: an update. Transfusion. 2019 Sep;59 Suppl 2:2018-2025.
  • Cai J, et al. The clinical safety of tranexamic acid: A systematic review and meta-analysis. J Thromb Haemost. 2020 Jan;18(1):153-162.