What is the mechanism of action of tranexamic acid (TXA) in pigmentation disorders, such as melasma?

Mechanism of Action of Tranexamic Acid in Pigmentation Disorders

Tranexamic acid (TXA) primarily works in pigmentation disorders like melasma by inhibiting plasminogen activation, which prevents the interaction between keratinocytes and melanocytes that leads to hyperpigmentation. 1

Primary Mechanism of Action

TXA is a synthetic derivative of the amino acid lysine that acts through several pathways:

1. Plasminogen/Plasmin System Inhibition:

   • TXA binds to lysine binding sites on plasminogen molecules, inhibiting the conversion of plasminogen to plasmin 1
   • This prevents plasmin from triggering melanocyte activation and melanin production

2. Vascular Effects:

   • Reduces vascular proliferation in melasma-affected skin 2
   • Decreases the number of CD31-positive vessels in the dermis 3
   • Lowers erythema index scores in affected areas 2

3. Mast Cell Reduction:

   • Significantly decreases mast cell counts in melasma lesions 2
   • Mast cells are known to release factors that stimulate melanogenesis

Molecular Pathways

TXA affects several molecular mediators involved in pigmentation:

• Endothelin-1 (ET-1) Suppression:

  • Downregulates ET-1, a paracrine factor that stimulates melanogenesis 3
  • ET-1 suppression is considered one of the key mechanisms in TXA's effect on melasma

• Vascular Endothelial Growth Factor (VEGF):

  • Reduces VEGF expression in melasma-affected skin 3
  • VEGF reduction contributes to decreased vascular proliferation

Histological Changes with TXA Treatment

TXA treatment leads to several observable histological changes:

• Epidermal Changes:

  • Significant reduction in epidermal pigmentation 2
  • Decreased melanin content as demonstrated by Fontana-Masson staining 3

• Dermal Changes:

  • Reversal of melasma-related dermal changes 2
  • Reduction in vessel numbers and mast cell counts

Clinical Efficacy

The mechanism translates to clinical effectiveness:

• Significant reduction in Melasma Area and Severity Index (MASI) scores 4, 5
• Improvement in skin lightening measured by objective methods like colorimetry 5
• Effective as both oral (250mg twice daily) and topical (2%) formulations 6, 3

Important Considerations and Cautions

• TXA is eliminated primarily through renal clearance, with approximately 90% excreted in urine within 24 hours 1
• Reduced doses are indicated in patients with chronic or acute renal failure due to increased risk of neurotoxicity and ocular toxicity 1
• TXA should be used with caution in patients on oral contraceptive pills due to potential thrombotic risk 1
• TXA is contraindicated in disseminated intravascular coagulation 1

Comparative Efficacy

• TXA has been shown to be effective in treating refractory melasma that hasn't responded to conventional topical therapies 4
• In some studies, intradermal PRP (platelet-rich plasma) has shown better results than intradermal TXA for melasma management 1
• TXA can be used as a safe and useful adjunct to other treatments for melasma 4

By targeting multiple pathways involved in melanogenesis and vascular components of melasma, TXA offers a unique mechanism of action that differs from traditional depigmenting agents like hydroquinone, which primarily inhibits tyrosinase enzyme activity.