Tranexamic acid (TA), a plasmin inhibitor, is a synthetic analog of the amino acid lysine [12]. TA reversibly blocks lysine-binding sites on plasminogen molecules and prevents plasminogen activator from converting plasminogen to plasmin [13, 14]. Plasmin is a protease that enhances the release of intracellular arachidonic acid and also increases levels of alpha-melanocyte-stimulating hormone (α-MSH). These two molecules are known to increase melanocyte synthesis of melanin [15].

TA inhibits UV-induced plasmin activity by preventing the binding of plasminogen to keratinocytes, which results in a decrease in free arachidonic acid and therefore a decrease in prostaglandins that are known to increase melanocyte tyrosinase activity [12, 15, 16]. Prostaglandins D₂, E₂, and F₂ have been reported to increase melanogenesis [12].

Mesotherapy using TA for melasma among Asians was first done in Korea. Eighty-five females with Fitzpatrick skin types IV to V completed an open-label pilot study, which involved weekly intradermal injections of 0.5 ml of TA (4 mg/ml) directly into the hyperpigmented lesions. Injections were spaced 1 cm apart after topical anesthesia was applied. The study ran for 12 weeks with clinical evaluation and MASI scoring done every 4 weeks. Subjective assessment was done using a patient satisfaction questionnaire at the end of week 12. Results showed a significant decrease in the MASI scores from baseline to 8 and 12 weeks (p < 0.05 for both). The authors observed that from week 8, there was a decrease in the darkness of the lesions followed by a decrease in the area of the hyperpigmented patches. However, only 8/85 patients (9.4 %) graded their improvement as good (51–75 % lightening), while majority of the patients (65/85, 76.5 %) graded their improvement as fair (26–50 % lightening). None graded their improvement as excellent (>75 % lightening), and 12/85 (14.1 %) graded themselves as poor (<25 % improvement). No significant side effects were noted [12].

A more recent study compared two methods of delivering TA on patients with melasma: through mesotherapy (microinjections) and microneedling. Microneedling is a minimally invasive procedure that involves passing a handheld device studded with numerous microneedles (frequently called a dermaroller) on the skin in order to create hundreds of microchannels where specific molecules or medications can be delivered transdermally. Normally, several passes are done on any given area, and the target medication/product is applied directly on the skin while these microchannels are still open. This facilitates entry into the skin of substances that would normally take longer or be more difficult to be absorbed topically such as proteins that would not otherwise pass through intact skin [15]. Microneedling has other dermatologic applications, most notably for skin rejuvenation and in the treatment of acne scars.

In this randomized open-label trial of 60 patients with Fitzpatrick skin types IV and V, half of the group (arm 1) received microinjections of TA (4 mg/ml) using a 4 mm meso needle into lesional skin. The other half (arm 2) underwent microneedling using a roller studded with fine needles 1.5 mm in length and 0.25 mm in diameter. After the skin was sufficiently wounded using the microneedles after four to five passes, the TA solution was directly applied on the skin, and the procedure was repeated for another four to five times. Treatments were done thrice at monthly intervals, and patients were followed up for another 3 months. Outcome measures included the mMASI score, physician and patient global assessments, and clinical photography. Both methods of delivering TA into the skin showed significant decreases in the mean mMASI scores from baseline to the end of the follow-up period. The arm treated with microneedling had more improvement but the difference between the two groups was not statistically significant. The authors attributed this finding to the ability of the microneedling device in achieving deeper and more even delivery of the medication [16].