The Efficacy of Platelet-rich Plasma Combined with Platelet-rich

Fibrin in the Treatment of Multiple Chronic Venous Leg Ulcer: A

Case Report

Primadhanty Bhadra, Indah Julianto, Mardiana, Adniana Nareswari, Halim Perdana, Endra Yustin

Ellista Sari

Department of Dermatovenereology Medical Faculty of Sebelas Maret University / Dr.Moewardi General Hospital

Surakarta, Central Java

Keywords: chronic Leg ulcer, platelet-rich plasma, platelet-rich fibrin, intralesional PRP injection.

Abstract : Chronic leg ulcer (CLU) is a defect in the skin below of knee persisting for more than six weeks and shows

no tendency to heal after three or more months. Leg ulcers occur in 1% of the adult population and 3.6% in

people over 65 years. It may increase with the onset of aging, people with atherosclerotic occlusion such as

smoker, obese and diabetic. A 55 years old woman, came with multiple ulcer in her left leg since 5 years

ago. There were various size of ulcers in her left leg, the largest size was 12x 9x 0. 1 cm and the smallest

one was 6x 6x 0. 1 cm with erythema base. On examination ankle brachial index (ABI) was 0. 9. Patient

was diagnosed with deep vein thrombosis (DVT) since 5 years ago, with no satisfying treatment.

Compression therapy is still the basic treatment for venous ulcers, but in our case, compression therapy was

not given satisfactory result. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) autologous are some

of the therapies that we can use in chronic wounds. Autologous PRP and PRF are contain many growth

factors (GF), that can help the healing process in chronic wounds, the treatments are easy to use, painless

and safe. In our case we used combined therapy of PRP and PRF for treating CLU and we also used

intralesional PRP injection for the initial treatment and results in satisfying improvement after 13 weeks

observation.

1 INTRODUCTION

Chronic leg ulcer (CLU) is characterized with a

chronic wound in the leg without healing after 3

months with proper treatment or not recovering

optimally at 12 month. Chronic leg ulcer (CLU)

common in adults and the symptoms usually include

pain, friable granulation tissue, foul odor, and

wound breakdown instead of healing. This result

social distress, considerable healthcare and personal

costs

(Shubhangi, 2013). In Chronic wound as in

CLU the levels of platelet derived growth factor

(PDGF), basic fibroblast growth factor (bFGF),

epidermal growth factor (EGF), and transforming

growth factor (TGF-) is reduced

(Sebastian, 2007).

Venous ulcer is the most common type of

chronic ulcer, with the incidence of 1-2 % in the

population. It is 75-80% of all vascular ulcers

(Braund, 2007). Heredity, age, female sex, obesity,

pregnancy, prolonged standing, and greater height

are the risk factors for the venous disease. At early

presentation, tenderness, edema, hyperpigmentation,

and varicose veins are typical features, at later stage,

atrophy blanched, lipodermatosclerosis and venous

ulcers

(Burkhart, 2008). Ankle Brachial Index

(ABI) score is usually used for assessing patient

with lower extremity venous insufficiency, the lower

score, means the more severe the arterial obstruction

(Sebastian, 2007). The conventional treatments of

vascular ulcers are leg elevation, compression, and

wound care. Topical steroids, aspirin, and surgery

are as second-line therapies. Autologous platelet-

rich plasma (PRP) is one of many treatment for

chronic leg ulcer, and it is promising therapy

(Braund, 2007).

PRP is a concentration of platelets required from

the patient's own blood which has been in

centrifugation. It contains ﬁbrin and high

concentrations of growth factors

(Yotsu, 2015). A

second-generation in platelet concentrate is PRF, it

is prepared from centrifuged blood, during

preparation we can find a ﬁbrin clot rich in platelets

510

Bhadra, P., Julianto, I., Mardiana, ., Nareswari, A., Perdana, H. and Sari, E.

The Efﬁcacy of Platelet-rich Plasma Combined with Platelet-rich Fibrin in the Treatment of Multiple Chronic Venous Leg Ulcer: A Case Report.

DOI: 10.5220/0008160905100513

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 510-513

ISBN: 978-989-758-494-7

without addition of thrombin, platelet-derived

growth factor and TGF-β has been identified in PRF.

Platelet-rich plasma (PRP) and PRF speed up wound

healing by promoting the healing process secondary

to its GF. These include plateletderived GF (αα,

ββ, and αβ) fibroblast GF, vascular endothelial GF,

epidermal GF, insulinlike GF, and transforming

GF, which are needed in chronic wound healing

(Suthar, 2018).

2 CASE

55 years old woman presented to the

Dermatovenereology Outpatient of Dr. Moewardi

General Hospital Surakarta with chief complaint of

multiple ulcer in her left leg since 5 years ago. Itchy

red spot appeared on her left leg, which later became

small wound and her leg skin changed into black.

The wound then enlarged as the time went by. She

then seeked medical help and was diagnosed with

stasis dermatitis. After 2 months there was no

improvement, she came back to the same hospital

and she was treated by internist as she was

diagnosed with DVT comfirmed USG Doppler, after

3 months of treatment with elastic bandage

(compression), aspilet

and venosmil

without

improving, a new small wound appeared in the same

leg. Because the wound enlarger, the doctor referred

patient to vascular surgery, and she had

debridement. She came back to her internist and she

was received additional therapy with simarc

amlodipine and candesartan

. However, the therapy

did not give satisfactory result, which made her to

came to our clinic.

This patient works as a shopkeeper who required

to stand for a long time. Physical examination

revealed high blood pressure 160/100 (hypertension

grade 1), Body Mass Index (BMI) 26. 6 (Obesity I),

the dorsalis pedis artery pulse was well palpable and

there was no specific finding in the laboratory

examinations.

The dermatological examination demonstrated,

multiple ulcer with the largest size of 9.5x 13x 0. 1

cm and the smallest one 6. 5x 6. 5x 0. 1 cm, at her

left leg varicose vein, hemosiderin and

lipodermatosclerosis also seen.

We treated the patient with PRP injection 0.

2cc/cm2 for initial therapy, after that we used the

topical PRP in antioxidant gel and we combined

with PRF for maintenance. We observed the patient

in every 3 days for 8 weeks months after that we

once a week. After 13 weeks of observation there

was satisfactory improvement.

Figure 1. (A-C). Multiple ulcer with the bigger size is 9. 5x 13x 0. 1 cm and the smallest size is 6. 5x 6. 5x 0. 1 cm. (D-F)

13 weeks of therapy with PRP combined PRF given every 3 days for 8 weeks, after that we once a week monthly.

The Efﬁcacy of Platelet-rich Plasma Combined with Platelet-rich Fibrin in the Treatment of Multiple Chronic Venous Leg Ulcer: A Case

Report

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3 DISCUSSION

One of the up to date modalities for CLU is PRP

(Hafner, 2012). Platelet-rich plasma (PRP) research

has long been studied for its the molecular

interaction of platelets and plasma secretion with

different cell phenotype. Platelet-rich plasma (PRP)

is promising therapy in wound care, as it increases

cell migration, proliferation, angiogenesis, and tissue

anabolism. Safe because free from antibody

formation, graft versus host’s disease and infectious

diseases such as hepatitis and HIV, easy and cost-

effective method with good results in the

management of chronic non healing ulcers are an

advantages of autologous PRP

(Alavi et al, 2016).

Aside from PRP we can use PRF, it also contains

fibroblast growth factor (GF), vascular endothelial

GF, angiopoitin and platelet-derived GF. These

speed up the wound healing

(Andiessen, 2017). He

L, et al in the statistical analysis levels reported that

TGF-β and PDGF-AB released from PRF or PRP at

different time points. PRP released the highest

amounts of TGF-β and PDGF-AB at the ﬁrst day,

followed by signiﬁcantly decreased release at later

time points PRF released the highest amount of

TGF-β at day 14

and the highest amount of PDGF-

AB at day 7

th.

(He, 2009). Choukroun et al. is the

first who develop PRF in France to be used in oral

and maxillofacial surgery, PRF belongs to a new

generation of platelet concentrates with simply

preparation and without any biochemical blood

handling

(Nagaraju, 2017). The intralesional

injection of platelet concentration constitutes a

valuable alternative in the treatment of chronic

ulcers

(Suthar, 2018).

Handling all possible systemic and local factors

which can interrupt healing process is the first step

in treating ulcers

(Hafner, 2012).Next eliminating or

treating the causes of precipitation, such as, surgical

intervention, until promotes circulation and

improves venous return, for example, compression

therapy. Wound care, lifestyle changes and symptom

management are needed for healing. Self-hygiene

promote preventive care is very important in

preventing its recurrence. Current treatments for

CLU include surgery, sclerotherapy, compress

therapy (conventional therapy), and adjuvant

pharmacotherapy

(Shubhangi, 2013). The mainstay

treatment for patients with venous leg ulcers is

compression therapy, there are 3 different techniques

in compression: (1) bandage system, (2) stockings

/socks, or (3) intermittent compression device,

however there an contraindications in the use of

compression therapy high compression of 40 mm Hg

should considered for a person with an adequate

vascular supply indicated by an ankle brachial

pressure index of 0.8 to 1.2 and in patients with

mixed arteriovenous ulceration (with an ankle

brachial pressure index [0.5 and an absolute ankle

pressure [60 mm Hg), inelastic compression \40 mm

Hg does not impede arterial perfusion and treats

impaired venous return

(Somani, 2017),

(Suryanarayan, 2014), (Moneib, 2017).

Our patient has multiple chronic wounds in her

left leg since 5 years ago, without any improvement

in the treatment, she was even treated with oral

therapy, compression therapy and debridement. The

diagnosis of DVT from this patient was confirmed

with physical examination, USG Doppler and ABI.

Hard to heal wounds are deﬁned as those with

granulation tissue which fail to epithelialize despite

two months of conservative treatment

(Burkhart,

2008). In this case, we can used PRP and PRF for

the treatment, as PRP and PRF can improved wound

healing through promotion of the healing process by

the presence of growth factor which are important in

modulating mesenchyme cell recruitment,

proliferation, and extracellular matrix synthesis

during the healing process

(Alavi et al, 2016). Beside

PRP and PRF we used injection PRP for the initial

therapy, this method accelerates the healing process

in the majority of non-healing wounds and

contributes to either the complete healing or the

preparation of the wound bed for a ﬁnal

reconstructive procedure

(Dionyssiou, 2012).

Platelet Rich Plasma (RPP) combined PRF given

every 3 days for 8 weeks, after that we once a week

monthly for 13 weeks. We are not use the

compression therapy because our patient felt pain

when using the bandage.

4 CONCLUSION

We acknowledge that this study was not funded by

any organization. There was no conflict of interest in

this study.

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