Injectable Platelet-Rich Fibrin Versus Intradermal Tranexamic Acid for Melasma

Melasma is a common chronic hyperpigmentation disorder characterized by symmetric brown to gray-brown patches, most commonly affecting the face. It is more frequent in women and in individuals with darker skin phototypes, and it may significantly impair psychosocial well-being and quality of life. Multiple pathogenic mechanisms have been implicated, including ultraviolet exposure, hormonal influences, genetic predisposition, melanocyte hyperactivity, and dermal vascular and inflammatory changes.

Current melasma therapies include topical depigmenting agents, chemical peels, laser and light-based procedures, and oral or local tranexamic acid. However, treatment response is often incomplete and recurrence is common. Intradermal tranexamic acid has shown promising results in reducing pigmentation through inhibition of plasmin activity and downstream melanocyte stimulation.

Injectable platelet-rich fibrin (i-PRF) is a second-generation autologous platelet concentrate prepared without anticoagulants. It provides a fibrin scaffold and gradual release of growth factors. Based on its biologic activity, i-PRF may have a therapeutic role in melasma by modulating melanogenesis, oxidative stress, and tissue repair. Despite this rationale, clinical evidence for i-PRF in melasma remains limited.

This study is a randomized split-face clinical trial designed to compare the efficacy and safety of i-PRF versus intradermal tranexamic acid in the treatment of facial melasma. Twenty-one adult female patients with mild to moderate bilateral symmetrical facial melasma, aged 18 to 50 years and with Fitzpatrick skin types III to IV, will be recruited from the outpatient dermatology clinic and cosmetology unit of Kasr El Ainy Hospital, Cairo University, Cairo, Egypt.

For each participant, one side of the face will be randomly assigned to receive i-PRF, while the contralateral side will receive intradermal tranexamic acid. Injectable platelet-rich fibrin (i-PRF) will be prepared from 10 mL of venous blood collected under aseptic conditions in a plain plastic tube and centrifuged at 60 g (700 rpm) for 3 minutes. The resulting i-PRF will be injected intradermally on the randomized side after topical anesthetic application. The opposite side will receive intradermal tranexamic acid prepared under aseptic conditions and injected at 1 cm intervals into melasma lesions. Participants will receive five treatment sessions at 2-week intervals. They will also be instructed to use broad-spectrum sunscreen and to avoid other topical facial treatments during the study period.

Both participants and outcome assessors will be blinded to the treatment allocation. Assessment will be performed at baseline and at the end of the study (Day 90). The primary outcome is the percent change in modified Melasma Area and Severity Index (mMASI) score from baseline to Day 90 between the i-PRF-treated side and the tranexamic-acid-treated side. Secondary outcomes include change in melanin level and vascular features measured by Antera 3D camera, Physician Global Assessment, patient satisfaction, global improvement scale, Melasma Quality of Life (MelasQoL) score, and adverse events.

Potential adverse effects include pain, tenderness, erythema, swelling, infection, ecchymosis, hematoma, and pigmentation changes. The study aims to determine whether i-PRF is an effective and safe therapeutic option for melasma compared with intradermal tranexamic acid.

Inclusion criteria

• Clinical diagnosis of bilateral symmetrical facial melasma (epidermal or mixed type)
• Female participants aged 18 to 50 years
• Fitzpatrick skin types III to IV
• Mild to moderate facial melasma
• No melasma-specific treatment within the previous 4 weeks
• No facial procedures, including peeling, laser resurfacing, or microneedling, within the previous 3 months
• Willing and able to provide written informed consent and comply with study procedures

Exclusion criteria

• Pregnancy or lactation
• Bleeding or coagulation disorders
• Use of anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), or hormonal contraception
• Active skin infection or facial inflammation
• History of keloids or Koebner-prone conditions, such as psoriasis or vitiligo
• Uncontrolled systemic disease, such as diabetes mellitus or autoimmune disease