Research Article ISSN 2690-537X

Research Article Dermatology Research

Efficacy and Safety of Autologous Platelets Concentrated in the Treatment

of Perioral Skin Aging
Israel Alfonso-Trujillo1, Yetter Cruz-Leon1, Melissa Johana Espitia-Cordero1, Eduardo Jesús Núñez-Jordán2,
Yaquelin Luciana Morales Novo3, Jesus Lazaro Diego-De la Campa4, Angela Rosa Gutierrez-Rojas5, Julio
Antonio López-Silva6 and Daymi Serpa-Almaguer7
1
Dermatology Specialist, Doctor of Medical Sciences, Professor and
Senior Researcher
Dermatology Resident, Clinical Surgical Hospital, Hermanos
2

Ameijeiras. Havana Cuba.

Graduate in Health Technology, Assistant Professor, Clinical Surgical
3 *
Correspondence:
Hospital: Hermanos Ameijeiras. Havana Cuba.
Israel Alfonso-Trujillo, Calzada de Managua # 1133 between
Specialist in Hematology, Assistant Professor, Clinical Surgical
4
Cayman and Quemados, Las Guásimas, Arroyo Naranjo,
Hospital: Hermanos Ameijeiras. Havana Cuba. Havana, Cuba, CP: 19320.
Specialist in Biostatistics, Assistant Professor, Clinical Surgical
5

Hospital: Hermanos Ameijeiras. Havana Cuba. Received: 02 May 2021; Published: 25 May 2021
Hematology Specialist, Assistant Professor, Clinical Surgical
6

Hospital: Hermanos Ameijeiras. Havana Cuba.

Immunology Specialist, Instructor Professor, Clinical Surgical
7

Hospital: Hermanos Ameijeiras. Havana Cuba.

Citation: Alfonso-Trujillo I, Cruz-Leon Y, Espitia-Cordero MJ, et al. Efficacy and Safety of Autologous Platelets Concentrated in the
Treatment of Perioral Skin Aging. Dermatol Res. 2021; 3(1): 1-6.

ABSTRACT
Introduction: The rejuvenation of the perioral region has a certain degree of difficulty. The search for painless and
minimally invasive alternatives is a challenge in the field of aesthetic medicine.

Objective: To evaluate the efficacy and safety of intradermal microinjection of autologous platelet concentrate
(APC) in the treatment of perioral skin aging signs.

Method: An observational, analytical and longitudinal study was carried out in 60 patients from the Hospital
Clínico Quirúrgico: “Hermanos Ameijeiras”, in the period between March 1, 2017 and March 31, 2020. The
treatment was applied monthly. For 1 year. The final evaluation was carried out 3 months after the end of the
treatment.

Results: 60 women with an average age of 45 ± 4.3 years were treated. After treatment, there were significant
changes in the Glogau Photo Damage Scale (P = 0.028), in the Global Aesthetic Improvement Scale (P <0.032)
and in the Evaluative Scale of the severity range of the nasolabial fold (P = 0.031). The adverse events found were
pain, inflammation and ecchymosis. The degree of satisfaction reported by the patients was good (16.7%) and very
good (83.8%) (P <0.038).

Conclusions: The autologous platelet concentrate proved to be effective and safe to reduce the signs of perioral
skin aging, associated with a high degree of patient satisfaction.

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Keywords
Platelet-rich plasma, Perioral rejuvenation, Perioral skin Exclusion criteria
photoaging, Autologous platelet concentrate.
Table 1: Exclusion criteria and their relationship with the time limits to
Introduction perform the procedure.
The rejuvenation of the perioral region must take into account the Criteria Time limits
Prior and simultaneous to the
three processes that accompany aging: loss of volume, ptosis (fall) Congenital or acquired coagulation disorders.
procedure.
and skin changes (wrinkles, atrophy, flaccidity, and dehydration), Prior and simultaneous to the
and processes that are closely related to each other. The loss Bone marrow aplasia.
procedure.
of volume can be corrected with fillers (hyaluronic acid and Prone to forming keloids. Before the procedure.
autologous fat). Ptosis can be improved with tensioning threads Cardiovascular or pacemaker, neurological,
Simultaneous to the procedure.
or lifting [1,2]. Skin changes have traditionally been treated with liver, kidney, endocrine or immunological
diseases, decompensated.
lasers, peels, mesotherapy (vitamins, minerals, and hyaluronic
Severe psychiatric disorder or other limitation
acid) and recently with regenerative therapy (platelet-rich plasma) that prevents the patient from giving his Simultaneous to the procedure.
[3,4]. informed consent or makes his evaluation
difficult.
Taking into account the pathophysiology of skin aging and the Pregnancy or breastfeeding Simultaneous to the procedure.
properties of platelets and their growth factors (GF), [5] its use Treatment with anticoagulants,
antifibrinolytics, macrolides, terfenadine, One month prior to the procedure.
to improve skin changes would be justified, however, few studies cimetidine, amiodarone, fluoxetine, NSAIDs,
objectively evaluate its efficacy and safety, which motivated the or corticosteroids.
realization of the present investigation. Application of topical retinoids, aesthetic
treatments in the region to be treated, Three months prior to the
including lasers, intense pulsed light, procedure.
Goals chemical peels, mesotherapy, carboxytherapy
The primary objective was: to determine the efficacy and safety or others.
of the microinjection of autologous platelet concentrate (APC) Fillers in the region to be treated. One year prior to the procedure.
in the treatment of perioral skin aging signs and the secondary Active neoplastic diseases or during the Five years post-healing prior to
objectives were: 1) to evaluate the clinical response to treatment, follow-up period the procedure.
2) to evaluate type and intensity of adverse events that occur and
3) describe the degree of patient satisfaction. Elimination criteria
Patients who wish to abandon the study, presence of an adverse
Method event and / or complication that prevents continuing with the
An observational, analytical, longitudinal study was carried out treatment or patients who have missed a treatment session.
in 60 patients at the Hospital Clínico Quirúrgico: “Hermanos
Ameijeiras”, in the period between March 1, 2017 and March 31, Treatment
2020. Once the patients gave informed consent, the included subject’s
registry template and the investigator's internal registry were filled
The treatment was applied monthly for 12 months. Three months out. The blood was extracted (500 milliliters), then the CPA was
after the end of the treatment, the response to it (final evaluation) was obtained with the Rotixa centrifuge (221 mm radius) according
evaluated, comparing the current state of the lesions (barcode, lips, to international standards [8]. To obtain the CPA, a first light
Cupid's bow, marionette wrinkles, nasolabial fold, pigmentations, centrifugation of the whole blood was carried out in the plastic
lentigos and querotosis) with the initial state; for this, the patient bag for 3 minutes at 2800 rpm at 22 oC, with a centrifugation force
had to attend the scheduled consultation. Throughout the study, of 2000 g, in this way 250 ml of red blood cells and 250 ml were
there was a rigorous control of adverse reactions. Before and after obtained. Platelet rich plasma (PRP); then a second weighted
the procedure, the platelets were quantified to determine the quality centrifugation was performed on the PRP in the plastic bag for
of the applied product (the average degree of concentration of the 5 minutes at 4500 rpm at 22 oC, with a centrifugation force of
platelets after the procedure increased 10.8 times its initial value). 5000 g. Once the heavy centrifugation had been carried out, the
Microbiological culture of the extracted plasma was performed to supernatant plasma was transferred through the tubes that have the
guarantee that a sterile germ product was administered. plastic bags for blood collection, only 10 ml were left, and it is
in said volume that by shaking the platelets that were deposited
Inclusion criteria in the cell were resuspended. Bottom of the bag as results of
Patients between 20 and 60 years old, of any sex and skin the centrifugation procedure. Subsequently, the red blood cells
phototype, skin photoaging grade II to IV (Glogau classification), were returned to the patients and finally a microinjection of 10
[6] nasolabial fold (NGS) grade 2 to 5 (evaluative scale of milliliters of the CPA was performed, distributed among the NGS,
severity range of the nasolabial fold), [7] normal complementary the entire facial area, V of the décolleté, neck and the back of the
examinations, with signed informed consent. hands. Subsequently, with a 25G × 16 mm hypodermic needle and

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1 ml syringes, intradermal injections of approximately 1.5 ml were Adverse Events
administered at a distance of 1.5 to 2 mm between each application Adverse events reported in the reviewed literature are pain, edema,
area (point-to-point, fan, backtrace and nappage). and ecchymosis at the microinjection site [4,5].

Variables related to the response to treatment Classification of adverse events (Table 5) [10]
The response to treatment was evaluated taking into account the
clinical examination of the patient, using the Glogau photodamage Table 5: Intensity scale of adverse events[10].
scale (Table 2), [6] evaluative scale of the severity range of the Intensity Characteristics
nasolabial fold (WSRS) (Table 3) [7] and the global aesthetic Mild If the adverse event subsided without treatment.
Moderate If treatment was required, but the adverse event subsided with it.
improvement scale (GAIS) (Table 4) [9].
Serious If he required hospitalization or did not yield to treatment.
If it endangered the life of the patient, if it caused sequelae or
Table 2: Classification of photoaging according to Glogau [6]. Very serious
disability.
Type Characterization
Early photoaging: slight pigmentary changes, no keratosis, Degree of satisfaction of patients to treatment
Type I
minimal wrinkles, no scars, young patient, generally 28-35
"No wrinkles"
years of age, no or minimal makeup.
The degree of satisfaction (PSSS) of the patients with the treatment
Early to moderate photoaging: visible early senile lentigo, was evaluated taking into account what was reported by the patient
Type II
early actinic keratosis, slight signs of scars, wrinkles and according to the scale (Table 6) [11].
"Movement
parallel smile lines begin to appear, patient age: late 30s or
wrinkles"
40s, usually she wears some makeup. Table 6: Scale of the degree of patient satisfaction [11].
Advanced photoaging: obvious dyschromia and
Evaluation Degree of satisfaction
Type III telangiectasias, visible keratoses, neoplasms (+), wrinkles
"Wrinkles at rest" even when not moving, patient age: fifty years or older, I did not get any improvement and the treatment caused
always wears a lot of makeup. 1 Very bad me multiple discomforts (inflammation, bruising and
pain).
Intense photoaging: grayish-yellow skin, cutaneous
Type IV neoplasms (+++), all wrinkled skin, no normal skin, age I did not get any improvement, but the treatment did not
2 Bad
"Wrinkles only" of patient: sixties or seventies, cannot wear makeup, "hard cause me any discomfort.
and cracked". 3 Regular The improvement was little.
4 Good. The improvement was noticeable, but not total.
Table 3: Evaluative scale of the severity range of the nasolabial fold 5 Very good The improvement was complete with minimal discomfort.
(WSRS) [7].
Grade Characteristics Bioethical considerations
Extremely large and deep furrows. Detrimental facial The protocol was submitted to the consideration and approval of
5 Extreme
appearance. The skin stretch shows a 2-4 mm deep V-shaped a Review and Ethics Committee for Clinical Research created
fold. It is unlikely to achieve a satisfactory correction with an
for this purpose, which evaluated it from an ethical point of
injectable implant.
Large deep furrows. Prominent facial manifestation. When
view. Additionally, this protocol was subjected to scientific
4 Severe the skin is stretched the fold is visible less than 2mm deep. and methodological review and approval by the Institutional
Significant improvement is expected with injectable implant. Scientific Council of the Hospital Clínico Quirúrgico “Hermanos
Moderately deep furrows. Clear and visible facial Ameijeiras”.
manifestation. The crease disappears when the skin is
3 Moderate
stretched. Excellent correction is expected with injectable
implant. Statistical methods used
Visible but superficial groove, like a slight footprint. Minor The medical records of the patients included in the study were
2 Slight facial manifestation. With an injectable implant, a slight stored in the Department's file. With the information gathered, a
improvement in appearance is expected. Microsoft Office version XP database in Excel format was created,
1 Absent No visible furrow, continuous skin line.
which was exported to the SPSS version 21.0 system for analysis.
To summarize the information of the study sample, the arithmetic
Table 4: Global aesthetic improvement scale (GAIS) [9].
mean, standard deviation and minimum and maximum values w ​​ ere
Evaluation Degree of improvement
used. For all quantitative variables, the student's t test was used.
Patient with exceptional or much better improvement
1 Total answer (excellent corrective result, total disappearance of the
For all qualitative variables (degree of photodamage, degree of
lesions). aesthetic improvement, degree of affectation of the severity of the
Patient greatly improved or considerably better nasolabial fold and degree of satisfaction), the absolute numbers
Marked partial
2 (marked improvement in appearance, but not completely and percentages were calculated, before and after the treatment,
response
optimal, reduction of lesions by ≥ 50% and <100%).
which were compared using the test. Pearson's Chi-square. In all
Improved or somewhat better patient (appearance
3
Slight partial
slightly better than initial condition, but needs more
hypothesis tests carried out, a significance level α = 0.05 was used.
response
treatments, <50% lesions decrease).
No, change (the same number and size of lesions as at Sample's size calculation
4 Non-response
the start of treatment). The sample size was calculated using the C4-Study Design Pack
5 Progression. Worse (increased number or size of lesions). computerized program. (C4- SDP) for sample size calculation

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(CTM). Version 1.1 ® Glaxo Wellcome. SA; [12] considering the
following values: percentage of success reported in the literature
70%, percentage of success in the current study of 80%. With an
alpha error of 0.05, a power of 80% and covering a loss of 5% of
the patients, it was necessary to have 60 subjects in total.

Results
The study sample consisted of 60 women with skin phototypes
between II and IV. The average age ranged around 45 ± 4.3 years
(Table 7). A B

Figure 1: Images showing the improvement of the skin on the perioral

Table 7: Epidemiological and clinical characteristics of the subjects. region of a patient (A) before and (B) three months after treatment with
Age Mean (SD) 45.6 (± 4.3) APC.
(Minimum;
(27; 58)
Maximum)
N %
20-29 15 25.0
30-39 12 20.0
40-49 27 45.0
50-60 6 10.0
Sex Female 60 100.0
Skin phototype II 24 40.0
III 33 55.0
IV 3 5.0
Glogau II 9 15.0 A B
III 51 85.0 Figure 2: Images showing the improvement of the skin on the perioral
WSRS 22 2 8 13.3 region of another patient (A) before and (B) three months after treatment
3 32 53.3 with APC.
4 12 20.0
E5 8 13.3 All the patients reported some adverse event (pain, inflammation
and ecchymosis), which were of slight intensity, did not imply
Regarding the Glogau Photodamage Scale, 51 patients were
changes before the intervention and were completely resolved. The
classified as grade III, and 9 as grade II before the start of the
pain occurred during the procedure and disappeared immediately
study. After treatment, 36/51 (70.6%) patients who were classified
after the completion of the procedure (100%), the inflammation
as grade III were reclassified as grade II and 5/9 (55.5%) patients
who were classified as grade II were reclassified as grade I (p = (83.3%) lasted 2 to 3 days and the ecchymosis at the puncture sites
0.028); the rest of the patients remained in the same grade assigned (66.6%) were of short duration (five to seven days in duration)
before treatment. (Table 8).

According to the Global Aesthetic Improvement Scale, there Table 8: Adverse events.
were significant changes after treatment (p <0.032); 8/60 (13.3%) APC
N = 60
patients achieved a total response, 32/60 (53.3%) patients achieved N%
a marked partial response, and 20/60 (33.3%) patients achieved a Pain 60 100.0
slight partial response. Adverse events Inflammation 50 83.3
Equimosis 40 66.6
Regarding the evaluative scale of the severity range of the Duration Less than 7 days 60 100.0
nasolabial fold (WSRS), 8 patients were classified as grade 5, 12 intensity Light 60 100.0
as grade 4, 32 as grade 3, 10 as grade 2 and 8 as grade 1, before Attitude No changes 60 100.0
the start of the study. After treatment, 4/8 (50.0%) patients who Result Resolved 60 100.0
were classified as grade 5 were reclassified as grade 4, 17/30
(56.6%) patients who were classified as grade 4 were reclassified Of the 60 patients treated with CPA, 10/60 patients (16.7%)
as grade 3, 9 / 14 (64.3%) patients who were classified as grade 3 reported a good level of satisfaction and 50/60 patients (83.8%)
were reclassified as grade 2 and 5/10 (50.0%) patients who were reported a very good level of satisfaction, due to the fact that they
classified as grade 2 were reclassified as grade 1 (p = 0.031); the achieved evident improvement with respect to their condition
rest of the patients remained in the same grade assigned before initial (Table 9).
treatment (Figures 1 and 2).

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Table 9: Degree of satisfaction, according to the patients' own satisfaction Kamakura T et al. Evaluated the efficacy of PRP plus basic
scale (PSSS). fibroblast growth factor (bFGF) in the treatment of wrinkles
APC
p and depressed areas of the skin of the face. Of the 2005 patients
Satisfaction N = 60
treated, 1,889 were women and 116 men. The mean age was
N %
48.2 years. The treated areas included 1461 nasolabial folds, 437
Regular 0 0
marionette lines, 1413 nasolabial folds, 253 mid-cheek folds. The
Good 10 16,7 <0.038 (χ2)
results indicated that the patient satisfaction level was 97.3% and
Very good 50 83,3
the investigator satisfaction level was 98.4%. The period for the
effectiveness of the therapy to become apparent was an average
Discussion of 65.4 days. PRP plus bFGF therapy resulted in a better WSRS
The typical changes in the appearance of facial aging are
grade. The average WSRS improvement was 0.55 degrees in the
secondary to the progressive effect of gravity on skin with less
light grade, 1.13 degrees in the moderate grade, 1.82 degrees in the
elastic properties, thinner and drier. This is reflected in vertical
severe grade, and 2.23 degrees in the extreme grade [19].
wrinkles on the skin of the lips known as "barcodes", in the loss
of lip volume and the definition of the linea alba and cupid's bow.
The corners of the lips and the tissues of the cheeks descend, In our study, 60 women with an average age of 45 ± 4.3 years
deepening the nasolabial folds and generating the marionette lines. were treated. After treatment, there were significant changes in the
Another important factor is bone resorption and adipose tissue Glogau Photo Damage Scale (P = 0.028), in the Global Aesthetic
ptosis, which causes natural facial furrows to deepen. The activity Improvement Scale (P <0.032) and in the Evaluative Scale of the
of the sebaceous glands decreases over the years causing drier severity range of the nasolabial fold (P = 0.031). The adverse
skin. Thinning of the skin causes the contraction of the underlying events found were pain, inflammation and ecchymosis. The degree
muscle to move to the surface in the form of wrinkles [13,14]. of satisfaction reported by the patients was good (16.7%) and
very good (83.8%) (P < 0.038), which is why it is concluded that
PRP is rich in multiple growth factors secreted by pla-granules of autologous platelet concentrate is effective and safe in reducing
activated platelets, such as platelet-derived growth factor (PDGF), signs of aging of the perioral region, associated with a high degree
transforming growth factor-β (TGF-β), vascular endothelial growth of patient satisfaction.
factor (VEGF) and insulin-like growth factor (IGF). It is believed
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