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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 196-202

Comparison between the efficacy of injection vs topical platelet-rich plasma as an adjuvant treatment of chronic venous ulcers


1 Department of Dermatology and Venereology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt
2 Department of Vascular Surgery, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt

Date of Submission09-Dec-2019
Date of Decision18-Dec-2019
Date of Acceptance26-Dec-2019
Date of Web Publication29-Jun-2020

Correspondence Address:
MD Maisa A Abdel Wahab
Cairo, 11828
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_107_19

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  Abstract 


Background Chronic venous ulcers are the most common type of leg ulcers and have a major influence on the quality of life and work productivity. Chronic nonhealing ulcers lack the needed growth factors and do not heal later. The use of platelet-rich plasma (PRP) is based on the fact that platelets contain many growth factors that have a well-known role in the course of ulcer repair.
Aim and objective The aim was to evaluate and compare the efficacy of autologous PRP injection or topical application in the treatment of chronic venous ulcers.
Patients and methods This study was conducted from April 2016 to January 2017 on 30 patients with chronic venous ulcer, who were divided into two equal groups: group A was treated by PRP injections in perilesional tissue, and group B was managed by topical application of PRP on the surface of the ulcer. Thereafter, the ulcers of both groups were covered with Vaseline gauze and then covered by thin elastic sheet without compression for six sessions with a 1-week interval between sessions.
Results The study showed marked improvement in patients treated with injection and topical application of PRP after six sessions, with no statistically significant difference between the two groups regarding pressure ulcer scale for healing (PUSH) tool. Moreover, there was no statistically significant difference in healing ratio between both the groups.
Conclusion PRP shows promise as an effective treatment in chronic venous ulcers by different methods of application. It is a safe, simple, and inexpensive without any adverse events.

Keywords: efficacy, platelet-rich plasma, venous ulcer


How to cite this article:
Ahmed Ibraheem AI, Kamel AM, Mohamed Kamel RO, Abdel Wahab MA. Comparison between the efficacy of injection vs topical platelet-rich plasma as an adjuvant treatment of chronic venous ulcers. Sci J Al-Azhar Med Fac Girls 2020;4:196-202

How to cite this URL:
Ahmed Ibraheem AI, Kamel AM, Mohamed Kamel RO, Abdel Wahab MA. Comparison between the efficacy of injection vs topical platelet-rich plasma as an adjuvant treatment of chronic venous ulcers. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 26];4:196-202. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/196/288261




  Introduction Top


Venous ulcers are the most common form of leg ulcers that have a major influence on patients’ quality of life and wounds that are believed to happen owing to incompetent venous valves of the legs [1].

They are the most devastating outcome of chronic venous insufficiency and venous hypertension. They account for nearly 80% of all lower leg ulcers [2].

The treatment of chronic venous leg ulcers consists of the treatment of the etiology and simultaneous local treatment of the ulcer, with the application of dressings, or factors that together promote restoration of the normal physiological healing course [3].

Platelet-rich plasma (PRP) is a volume of autologous plasma that has a platelet concentration above baseline, which contains many growth factors (GFs) in their alpha granules. These factors have a well-recognized role in the process of tissue repair [4],[5].

Therefore, PRP is used as an adjuvant in the treatment of chronic ulcers of the lower extremity [6].

Moreover, the leukocytes present in the PRP increase its antibacterial properties. Previous studies of PRP have demonstrated antimicrobial activity against Escherichia coli, Staphylococcus aureus, including methicillin-resistant S. aureus, Candida albicans, and Cryptococcus neoformans [7],[8].

Autologous PRP may inhibit cytokine secretion, thus cause restrictive inflammatory reaction, whereas interactions with macrophages increase tissue healing and regeneration, stimulate growth capillaries, and accelerate epithelial repair [9].

PRP is used either as a topical gel or as injections. Platelet-rich fibrin matrix, a viscous fibrin meshwork rich in GFs, results in faster healing and increases re-epithelialization [10].

The aim of this study was to compare the efficacy of autologous PRP injection and topical autologous PRP in the treatment of chronic venous ulcers.


  Patients and methods Top


This is an interventional study conducted on 30 patients who were selected by simple random technique among patients with noninfected chronic venous ulcer for more than 6-week duration based on clinical and radiological diagnosis who attended the outpatient clinic for Vascular Surgery and Dermatology Clinics in Al Zahra University Hospital from April 2016 to January 2017. They fulfilled the inclusion and exclusion criteria, and then were subdivided into two groups who received different regimens of treatment, and a single-blind statistical analysis was done. The study was approved by the Ethical Committee of Al Azhar University.

Inclusion criteria

The following were the inclusion criteria:
  1. Age greater than 18 years.
  2. Patients with chronic venous leg ulcers more than 6 weeks.
  3. Patients should stopped any treatment for ulcer for 1 week.


Exclusion criteria

  1. Ulcers of others etiology such as traumatic and ischemic.
  2. Infected ulcer.


Clinical diagnosis of venous ulcers is generally irregular, shallow, painful, and located over bony prominences, particularly in the gaiter area (over medial malleolus), with granulation tissue present in the ulcer base. Other findings include lower extremity varicosities; edema; venous dermatitis associated with hyperpigmentation; and lipodermatosclerosis associated with thickening and fibrosis of normal adipose tissue under skin [11].

Radiological diagnosis was done by venous duplex imaging, which provides information about the valve dysfunction (incompetence valve):
  1. The presence of reflux is determined by the reverse direction of flow.
  2. A reflux time of greater than 0.5 s.


Longer duration of reflux implies more severe disease [12].

All patients, after approval and full explanation about the new procedure, were subjected to complete blood picture, prothrombin time, and clinical examination of ulcer, especially measurement of its size according to pressure ulcer scale and taking photographs before and after the start of treatment.

The patients were divided into two equal groups (A and B), which were treated with either PRP injection or topical respectively for six sessions with a 1-week interval between sessions. Then every week the ulcer area was calculated using pressure ulcer scale for healing (PUSH), which ranged from 0 to 17, with lower scores indicating the better wound condition.

Steps of platelet-rich plasma preparation

  1. Under aseptic precautions, 10 ml of venous blood was withdrawn from antecubital vein of the patient and put in four tubes containing sodium citrate as an anticoagulant.
  2. First centrifugation was done using a laboratorial centrifuge Gemmy table top centrifuge (PLC-01, PLC-02, PLC-03, PLC-04, PLC-05) with the speed of 5000 round per minute for 15 min at room temperature. This led to separation of the sample to three layers from above downwards: the plasma layer, then the buffy coat layer, and then red blood cells layer.
  3. The plasma and buffy coat were pipetted and transferred to other 5 ml vacuum tube, and then the sample was exposed to a new centrifugation cycle with the speed of 2000 round per minute for 10 min. This led to a separation of two layers: above platelet poor plasma and below PRP.


In group A, PRP layer was separated and then activated by adding 0.05 ml Ca chloride 10% to each 1 ml PRP in insulin syringe, and then it is ready for use within 10 min. Injection of two-thirds of the volume of PRP was done into the perilesional tissue of the ulcer, with topical application of the remaining third to the surface.

In group B, PRP layer was separated and then activated by adding 0.3 ml Ca chloride 10% to each 1 ml PRP in a sterile empty tube, which was then left for 15 min, and then it was ready for use as a topical application on the surface of the ulcer.

Then the ulcers in both group were covered with Vaseline gauze and thin elastic sheet without compression, only to keep the plasma intact with the wound. The sessions were repeated weekly for six times.

Follow up

The patients in the two groups were compared regarding reduction in the size of the ulcer area (PUSH score). PUSH was developed by the Nation of Pressure Ulcer Advisory Panel to monitor the change in pressure ulcer status over time. The tool consists of three parameters: wound surface area (ranging from 0 to 10), exudate amount (ranging from 0 to 3), and tissue type (ranging from 0 to 4). The scores of three question can be summed to give a total score ranging from 0 to 17, with lower scores indicating better wound condition ([Table 1]) [13].
Table 1 Pressure ulcer scale for healing (PUSH)

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[Figure 1],[Figure 2],[Figure 3],[Figure 4] illustrate the treatment follow-up by injection and topical PRP, respectively.
Figure 1 (a) Case of injection platelet-rich plasma. The ulcer before the treatment; it measured 3×1 cm, with pressure ulcer scale for healing score of 8. (b) Case of injection platelet-rich plasma. The ulcer at the fourth visit after third week treatment; it measured 1×1 cm, with pressure ulcer scale for healing score of 5. (c) Case of injection platelet-rich plasma. The ulcer at seventh visit after six sessions of injection platelet-rich plasma; it completely healed, with pressure ulcer scale for healing score of 0.

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Figure 2 (a) Case of injection platelet-rich plasma. The ulcer before the treatment; it measured 3×2.5 cm, with pressure ulcer scale for healing score of 10. (b) Case of injection platelet-rich plasma. The ulcer at the fourth visit after 3rd week treatment; it measured 2×1.5 cm, with pressure ulcer scale for healing score of 7. (c) Case of injection platelet-rich plasma. The ulcer at seventh visit after six sessions of injection platelet-rich plasma; it measured 1×1 cm, with pressure ulcer scale for healing score of 5.

Click here to view
Figure 3 (a) Case of topical platelet-rich plasma. The ulcer before the treatment; it measured 2×1.5 cm, with pressure ulcer scale for healing score of 8. (b) Case of topical platelet-rich plasma. The ulcer at the fourth visit after third week treatment; it measured 1.5×1 cm, with pressure ulcer scale for healing score of 6. (c) Case of topical platelet-rich plasma. The ulcer at seventh visit after six sessions of topical platelet-rich plasma, with pressure ulcer scale for healing score of 0.

Click here to view
Figure 4 (a) Case of topical platelet-rich plasma. (a) The ulcer before the treatment; it measured 7×4.5 cm, and pressure ulcer scale for healing score was 13. (b) Case of topical platelet-rich plasma. The ulcer at the fourth visit after third week treatment; it measured 6×2 cm, and pressure ulcer scale for healing score was 10. (c) Case of topical platelet-rich plasma. The ulcer at seventh visit after six sessions of topical platelet-rich plasma; it measured 4×.5 cm, and the pressure ulcer scale for healing score was 6.

Click here to view


Statistical data and analysis

The collected data were coded and introduced to Statistical Package for the Social Sciences (SPSS 15.0.1, USA), with P less than 0.05 considered significant.


  Results Top


This study was conducted on 30 patients with chronic lower limb venous ulcer. They were divided into two groups (A and B). Each group included 15 patients who were treated with either an injection or topical application of PRP for six sessions, with a 1-week interval between sessions.

There was no statistically significant difference between the two groups regarding personal and medical data, as shown in [Table 2].
Table 2 Comparison between the two groups regarding personal and medical data

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Moreover, there was no statistically significant difference in healing ratio between two groups, as shown in [Table 3].
Table 3 Comparison of healing ratio of ulcers before and after treatment among both groups

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There was a highly statistically significant difference between the two groups regarding PUSH score before and after PRP application, as shown in [Table 4].
Table 4 The difference between pressure ulcer scale for healing before and after injection and topical platelet-rich plasma

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There was no statistically significant difference in treatment outcome between group A (injection) and group B (topical), as complete healing ratio (47%) was equal in both groups ([Table 5]).
Table 5 Comparison of treatment outcome after 6 weeks between two groups

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The distribution of healing ratio is the same across categories of injection or topical treatment of venous ulcers, with no statistically significant difference ([Table 6]).
Table 6 Statistical hypothesis testing

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Cases

[Figure 1] and [Figure 2] illustrate the treatment and follow-up by injection PRP while [Figure 3] and [Figure 4] illustrate the treatment and follow-up by topical PRP.


  Discussion Top


PRP enhances wound healing by stimulating the healing process owing to the GFs present in it [14].

This study was conducted on 30 patients with chronic leg venous ulcers. They were divided into two equal groups, which were treated with either an injection or topical PRP to evaluate and compare the efficacy of treatment between the two groups. The results showed improvement in healing, with no statistically significant difference between the two groups after 6 weeks of treatment. The mean percentage of ulcers healing was 62.22 and 68.45% in groups A and B, respectively, with complete healing ratio of 47%, being equal in both groups.

In agreement with our study, the results of the study conducted by Frykberg et al. [15] on 49 patients with 65 nonhealing ulcers showed that 63 of 65 ulcers responded to topical PRP therapy, with a decrease in the ulcers area being 56.1% in a mean of 2.8 weeks.

Sarvajnamurthy et al. [16] conducted a study on 12 patients with 17 chronic venous ulcers who were treated with topical PRP and reported that the mean duration of the healing of the ulcers was 5.1 weeks, with marked improvement in the area and volume of the ulcer. Overall, 100% improvement in the area of the ulcers was seen in 13 (76%), and 100% improvement in volume of the ulcer was seen in 14 (82%) in patients treated with PRP for six sessions. The mean percentage improvement in the area and volume of the ulcer was 94.7% (SD: 11.12).

In a study of Suryanarayan et al. [17], 24 patients with 33 ulcers were treated with topical PRP at weekly intervals for a maximum of six treatments, and the mean duration of healing of the ulcers was 5.6 weeks (SD: 3.23). The mean percentage of reduction in area and volume of the ulcers was 91.7% (SD 18.4%). Aguirre and colleagues treated 23 patients with 23 nonhealing chronic venous leg ulcers with autologous PRP for eight session held at a week interval. Two-thirds of PRP was injected in perilesional tissue, with application of the other one-third topically on ulcer surface. They showed marked reduction in size of the ulcers, and the mean percentage of healed surface of the ulcers size was 81.8% (SD: 9.3). Among which five ulcers healed completely within 4 weeks, and they reported no complications occurred in any patient.

In a study of Salazar-Álvarez et al. [18], 11 patients with 11 nonhealing ulcers had been treated with PRP for more than 6 weeks at weekly intervals for a maximum of six treatments. Two-thirds of PRP was injected in perilesional tissue with application the other one-third topically on ulcer surface. They showed marked reduction in area and volume of the ulcers, and the mean percentage of reduction of ulcer size was 60%, and complete healing was achieved in five cases. No adverse effects were observed.Moreover, there were no adverse effects associated with the application of PRP, except there was pain during injection PRP in perilesional tissue, which can be avoided by local anesthesia. Sarvajnamurthy et al. [16] stated that PRP is a safe, simple, effective, inexpensive, and biocompatible procedure in treating chronic venous ulcers.


  Conclusion Top


PRP is a safe, simple, and inexpensive treatment and improves wound healing in chronic venous leg ulcers by different methods of application.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Frykberg RG, Driver VR, Carman D, Lucero B, Borris-Hale C, Fylling CP et al. Chronic wounds treated with a physiologically relevant concentration of platelet-rich plasma gel: a prospective case series. Ostomy Wound Manage 2010; 56:36–44.  Back to cited text no. 15
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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