Project benefits of the use of Tranexamic acid (TXA)

Project Summary/Proposal

Topic: Tranexamic Acid in
Melasma Treatment

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Student Name:  Salman Ahmad

MSc Dermatology in Clinical
Practice

University of South Wales

Date of Submission: 2 March
2018

 

Background and Introduction:

 A common pigmentary condition, melasma, is
best defined as localized, chronic – acquired hyper melanosis of the skin
characterized by light to dark brown macules and patches symmetrically
involving the sun-exposed areas of the face, neck and occasionally the
forearms. It is commonly observed in reproductive age group women, rarely in
postmenopausal females and males (10% of cases). Causative factors implicated
in the melisma pathogenesis include genetic susceptibility, ultraviolet (UV)
light exposure, pregnancy, sex hormones, contraceptive pills, thyroid disease,
cosmetics, phototoxic drugs (e.g., antiseizure medications).(Grimes PE,1995)(Park
et al,2017)

There are three clinical
patterns of melasma, malar (most common), centro facial and mandibular. On the
basis of visible light, wood’s light and lesional histology, melasma has been
classified as epidermal, which has increased melanin predominantly in basal and
suprabasal layers of the epidermis with pigment accentuation on Wood’s lamp.
The dermal type has perivascular melanin-laden macrophages in the superficial
and deep dermis and does not accentuate with Wood’s lamp. The mixed variety has
elements of both and appears as deep brown colors with Wood’s lamp accentuation
of only the epidermal component.(Sanchez NP et al,1981)

Melasma is well known for treatment resistance and relapses
on treatment discontinuation.Melasma is found to
be refractory to treatment, with a tendency to recur after treatment.
There is not a single satisfactory treatment modality to date.(Del Rosario E., et al, 2018) 

In melasma treatment, the
introduction of tranexamic acid ( oral, topical or intralesional) is relatively
a novel concept. The skin?whitening
effects of Tranexamic acid were incidentally found when it was used in the
treatment of aneurysmal subarachnoid hemorrhage. Nijor from Japan,1979 first
reported Tranexamic Acid to be effective in melasma treatment.

Objective:

 This dissertation proposal seeks to offer
therapeutic benefits of the use of Tranexamic acid (TXA) as an innovative
agent, either as an oral, topical or intralesional method for melasma
treatment.

Importance of this Proposal:
Tranexamic acid being originally a hemostatic agent. Its use in treating and
gaining clinical benefits in Melasma treatment is not highly documented and
there is scope for establishing and validating Tranexamic acid with accurate,
medically focused perspectives.

Hypothesis:

HI: Alternative hypothesis:
There have been medically documented and validated evidence that smaller doses
use of Tranexamic acid (250 mg BD) has a beneficial role in Melasma
Treatment(Poojary & Minni, 2015). 

 HO: Null Hypothesis: There is no medical
evidence to even remotely suggest that smaller doses use of Tranexamic acid
(250 mg BD) has a beneficial role in Melasma Treatment.

Methodology:

 This Proposal uses the qualitative method of
research, to achieve the quantum of literature, findings, and studies to
ascertain research question, as the first step. 
The literature used is secondary sources such as trial proceedings of peers
and data from published papers on the effect of TXA treatment on Melasma. All
of the referenced publications will be no older than 10 years and will not have
a low rating. In the next step, the author will infeG1 r from the research and use the new-found
knowledge to address the use of TXA. G2 

 Methods: The first phase of the research will
investigate literature on the chosen topic to establish the effects of
administering Tranexamic acid on Melasma treatment. 

 At the outset, it is important to understand
Melasma as a disorder and explore the reasons for its occurrence. Melasma is a
pigmentation disorder and is common among women of Hispanic and Asian groups.
The etiology of melasma has yet to be established, and the course of treatment
continues to be a challenge.

Treatment modalities include
use of hypo pigmenting agents such as hydroquinone, tretinoin, topical
corticosteroids, superficial peeling (lactic acid, glycolic acid,
trichloroacetic acid and kojic acid), LASERS (including Q-switched ruby laser,
Q-switched Alexandrite laser, erbium: yttrium-aluminum-garnet (Er: YAG) laser,
Fraxel laser, and intense pulsed light.(Gupta AK et al,2006)

Despite the availability of these therapies, melasma is
often recalcitrant to treatment, melasma poses
a great challenge as its treatment can be often unsatisfactory with high
recurrence rates.(Prignano F et al,2007)

Additionally, the success
rates of all these procedures are considered paradoxical darkening and low,
apart from their recognizable side-effects.

  Journal paper by Budamakuntla L., et al.,
titled “A Randomized, Open-label, Comparative Study of Tranexamic Acid
Microinjections’ and Tranexamic Acid with Microneedling in Patients with
Melasma”,

Cho, Choi, Cho, and Lee titled
“Role of oral tranexamic acid in melasma patients treated with IPL and low
fluence QS ND: Yag laser.G3 

Karn et al, 2012 concluded addition of oral Tranexamic acid to routine
treatment measures provide a rapid and better lightning in patients with
melasma. Low dose oral Tranexamic acid is thus recommended for melasma
treatment.G4 G5 G6 G7 

Aamir
S.et al, 2014G8  concluded
a rapid and sustained improvement can be provided with the introduction of tranexamic
acid in melasma treatment which none of the existing treatment modalities for
melasma has provided till date. G9 G10 G11 

Na Ji, et al., titled”
Effect of tranexamic acid on melasma- a clinical trial with Histological
evaluation”

Ebrahim Naeini study called
“Topical tranexamic acid as a promising treatment for melasma”.

 Anju George (2015) review article in Journal
Pigment International, established that Tranexamic acid is an effective
depigmenting agent as it is a synthetic derivative of lysine amino acid and
useful in arresting the conversion of plasminogen into plasmin (inhibiting
plasminogen activator). The result is a lower production of arachidonic acid
and thereby lowering prostaglandin levels. Thus, Tranexamic acid becomes
responsible for lowered melanocyte tyrosinase activity and therefore, useful in
treating melasma or UV-induced hyperpigmentation.

AWM Tan et al, 2016 concluded low-dose
oral Tranexamic acid can serve as a safe and useful adjunct in the treatment of
refractory melasma. How Tranexamic acid works in lightening melasma is unknown,
but it is possibly by modulating keratinocyte-melanocyte interactions and by
reducing vascularity in melasma lesions and through its effects on mast cells.

 

Padhi T et al,2015 concluded oral tranexamic acid can be
used as an adjunct with fluocinolone based triple combination cream for the
faster and sustained improvement in melasma treatment.G12 G13 

 

Del Rosario E, Florez- Pollack
S, Zapata Jr. L, Hernandez K, Tovar-Garza A, Rodrigues M, Hynan LS, Pandya AG’s
(2017), “Randomized, placebo-controlled, double-blind study of oral
tranexamic acid in the treatment of moderate to severe melasma” treated
250mg of TA/placebo capsules (2 times a day, for three months) to 44 patients.
39 completed the study and the primary outcomes were the Modified Melasma Area
and the Severity Index (mMASI) score showing 49% lower mMASI in TA group and
18% in the control group. Severe melasma showed higher rates of improvement
over moderate melasma. Further, after treatment stopped for three months, there
was 26% reduction in mMASI in the TA Group, over the baseline results.
Additionally, they witnessed 19% reduction in the placebo arm and reported no
adverse events in both the groups. Hence, this study established that oral TXA
was effective and superior to placebo in patients who had moderate to severe
melasma, and thus ideal alternative to standard therapies. The limitations of
this group were:  the study was conducted
at a single center where patient demography was predominantly Hispanic women.

 Other studies which tested the efficacy of
oral Tranexamic acid vs Triple combination for melasma treatment ( Neerja Puri,
2015) and concluded that recurring melasma is satisfactorily treated with oral
TXA in comparison to the combination of other modalities. 

Expected Outcomes

The therapeutic benefits of
the use of Tranexamic acid (TXA), as an innovative agent, either as an oral,
topical or intralesional method for the treatment of melasma

Gnat Chart

January- February: Proposal
writing create a list of potential studies to review.

February-March: Initial review
of primary resources with best results on use of TXA for melasma

March– April: Establish
outline by cross-references and secondary data from journal articles, studies

June – July: Propose the best
way to arrive at proposal objective 

July – August: Submit Thesis

 

Recommendation:

From the research studies
listed above and literature review, it can be said that Tranexamic acid as a
liposomal topical formulation, Intralesional/Intradermal Injection of
Tranexamic acid and Low-dose oral Tranexamic acid can be a safe and effective
alternative for treating refractory melasma.

 

Conclusion:

Across the nearly 30 journal
articles, books, review articles on the therapeutic effects of Tranexamic acid
in melasma, the conclusion that can be drawn is as follows: Topical ,
Intralesional and low dose oral Tranexamic Acid is highly useful in treating refractory
melasma.

 

Limitations of study: The
research includes the study of two different demographics – Hispanic and
Asians. Therefore, the results of the studies vary in terms of moderate or high
rates of success, is subjective to the population where the study was
conducted.

References:

 

·        
Grimes PE (1995) Melasma. Etiologic and therapeutic considerations.Arch
Dermatol 131: 1453-1457.

 

·        
Sanchez NP, Pathak MA, Sato S et al. Melasma: A clinical, light
microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol
1981;4:698- 710.

 

 

·        
Park, K.C., and Kim, I.S., 2017. Pathogenesis of Melasma. In Melasma and
Vitiligo in Brown Skin (pp. 21-31). Springer India.

 

·        
Gupta AK, Gover MD, Nouri K, Taylor S. Treatment of melasma: A review of
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·        
Prignano F, Ortonne J, Buggiani G, Lotti T. Therapeutical approaches in
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·        
Del Rosario, E., Florez-Pollack, S., Zapata, L., Hernandez, K.,
Tovar-Garza, A., Rodrigues, M., Hynan, L.S. and Pandya, A.G., 2018. Randomized,
placebo-controlled, double-blind study of oral tranexamic acid in the treatment
of moderate-to-severe melasma. Journal of the American Academy of Dermatology,
78(2), pp.363-369.

 

·        
Nijor T. Treatment of melasma with tranexamic acid. Clin Res
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·        
Aamir, S. and Naseem, R., 2014. The oral tranexamic acid in the
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·        
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Budamakuntla, L., Loganathan, E., Suresh, D.H., Shanmugam, S.,
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