Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 32  |  Issue : 2  |  Page : 723--728

The role of autologous platelet-rich plasma in healing of gaping and chronic wounds


Mohamed A Megahed1, Tarek M Rageh2, Ahmed T Nassar1, Mohamed El-Sayed Abdel Razek3,  
1 Department of Plastic Surgery, Menoufia University, Shebin El Kom Teaching Hospital, Shebin El Kom, Egypt
2 Department of General Surgery Department, Menoufia University, Shebin El Kom Teaching Hospital, Shebin El Kom, Egypt
3 Department of Plastic Surgery Department, Shebin El Kom Teaching Hospital, Shebin El Kom, Egypt

Correspondence Address:
Mohamed El-Sayed Abdel Razek
Tanta
Egypt

Abstract

Objective The aim was to evaluate the efficacy of platelet-rich plasma (PRP) in the treatment of gaping and chronic wounds. Background Nonhealing ulcers are a major health problem with high cost in terms of human and material resources. Application of autologous PRP has been a major breakthrough for the treatment of nonhealing ulcers, as it is an easy and cost-effective method and provides the necessary growth factors that enhance wound healing. Patients and methods A study was performed on 28 patients with nonhealing ulcers of various etiologies. Overall, 19 patients were treated with PRP at weekly intervals for a maximum of seven treatments and nine patients were treated with saline gauze dressings on alternative days. At the end of the 7, 14, 21, and 28-day periods, reduction in size of the ulcers (area and volume) was assessed and followed up till the healing completed, and the patients were followed up for a period of 12 weeks after treatment. Results The mean age ± SD of the patients was 39.68 ± 12.11 years. Of 19 ulcers in study group, there were two venous ulcers, nine traumatic ulcers, five pressure ulcers, and three diabetic ulcers. The mean ± SD duration of healing of the ulcers was 49.84 ± 22.23 days in study group and 108.67 ± 5.64 days in control group (P < 0.001). Conclusion Conventional therapies do not provide satisfactory healing for chronic nonhealing ulcers as they are not able to provide the necessary growth factors essential for the healing process. PRP is a safe, affordable, biocompatible, and simple office-based procedure for the treatment of nonhealing ulcers.



How to cite this article:
Megahed MA, Rageh TM, Nassar AT, Abdel Razek ME. The role of autologous platelet-rich plasma in healing of gaping and chronic wounds.Menoufia Med J 2019;32:723-728


How to cite this URL:
Megahed MA, Rageh TM, Nassar AT, Abdel Razek ME. The role of autologous platelet-rich plasma in healing of gaping and chronic wounds. Menoufia Med J [serial online] 2019 [cited 2019 Dec 10 ];32:723-728
Available from: http://www.mmj.eg.net/text.asp?2019/32/2/723/260899


Full Text



 Introduction



Wound healing is a complex process mediated by interacting molecular signals involving mediators and cellular events. It is followed by mesenchymal cell recruitment, proliferation, and extracellular matrix generation, which allows for scar formation. These events are mediated and modulated by interacting molecular signals, primarily cytokines, and growth factors (GFs) that stimulate and modulate the main cellular activities that underscore the healing process[1],[2]. Several studies have demonstrated that chronic wounds may, in some cases, lack GFs owing to decreased production, decreased release, trapping, excess degeneration, or an association of these mechanisms[3],[4].

Platelet-rich plasma (PRP) is a modern treatment strategy with worldwide recognition. Platelets play two important roles in wound healing: hemostasis and initiation of wound healing. After platelet activation and clot formation, GFs are released from α-granules located in the thrombocyte cell membrane. GFs work as biologic mediators to promote cellular activity by binding to specific cell surface receptors[5].

PRP is defined as plasma containing above-baseline concentrations of platelets which is from 140 000–400 000/μl. PRP is isolated through the centrifugation of whole blood and the resultant density-based separation of its contents. Simply put it, its actions are based on the infusion of elevated platelets, thereby theoretically enhancing the biological healing capacity and tissue generation in the wound bed. Enzyme-linked immunosorbent assay studies of PRP have quantified the presence of 7-, 10-, and 30-fold increases in GFs such as transforming GF β, epidermal GF, and platelet-derived GF[6].

In physiological conditions, through activation of platelets, these cytokines and GFs are transformed into their bioactive status and actively secreted within 10 min after clotting, with more than 95% of the presynthesized GFs released within 1 h. This process can be reproduced in clinical settings through activation of PRP by using an activator, for example, thrombin, resulting in the formation of platelet gel. This gel acts as a drug delivery system as it comprises a high concentration of platelets and their active cytokines and GFs, which stimulate physiological processes[7].

Because of this potential benefit, clinicians have begun to inject PRP for the treatment of tendon, ligament, muscle, and cartilage injuries and early osteoarthritis[8]. PRP may be used for the treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment, and the hospital stay. These procedures may be performed in outpatient clinics.

There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated[9].

Aim

The aim of this study was to evaluate the clinical and pathological efficacy of autologous PRP on healing of gaping and chronic wounds when applied regionally and topically.

 Patients and Methods



This study was done at Menoufia University and Shebin El Kom Teaching Hospitals between January 2017 and December 2017. The study included 28 patients with chronic wounds of different causes. The patients were of both sexes, with mean ± SD age of 39.68 ± 12.11 years. The patients were divided in two groups: one group (study group n = 19) was treated with autologous PRP as injection and surface application at the wound and the other one (control group n = 9) treated only with the ordinary methods of dressing.

Informed consent was taken from all patients after detailed description of the procedure before entry to the study. Approval by the ethical committee was obtained before initiating this study. The inclusion criteria were chronic wounds with a duration of more than 4 weeks that had not shown any progress.

Exclusion criteria were as follows:

Chronic wounds proved to be malignant by biopsySerologically positive patients for AIDSOsteomyelitisAcute or chronic ischemia.

Patients receiving drugs that negatively affect wound healing (such as steroids or chemotherapy).

Patients with known coagulation defects, thrombocytopenia, smokers, or pregnancy.

Wounds were measured at day 0 with tape in two largest perpendicular diameters and multiplied to obtain the area in cm2, and initial photography was taken.

Measurements of the ulcers size and photography were routinely taken on day 7, 14, 21, and 28. Deep tissue culture and systemic antibiotics according to culture sensitivity were given before starting the PRP therapy.

Plan of study

The patients were divided into two treatment groups: (a) study group: (PRP group) – chronic wound was cleaned with normal saline, and PRP solution was injected in and around the wound. PRP gel was evenly distributed over the wound. Dressings were done once a week and changed depending on the wound exudate. (b) Control group: the ulcers were first cleaned and then normal saline dressings were done. Dressings were changed on alternate days.

Platelet-rich plasma preparation

After obtaining signed informed consent, according to the size of the wound, 10–60 ml of venous blood was taken and anticoagulated by acid citrate dextrose. PRP was prepared by double centrifugation method. The first spin used was hard spin (3000 rpm for 15 min) which separates into three layers: plasma, buffy coat, and red blood cells. The plasma and buffy coat was aspirated into a sterile test tube without an anticoagulant and subjected to a second spin (2000 rpm for 5 min); this centrifuge separates platelet-poor plasma (PPP) in the upper part and PRP in the lower part. PPP was discarded. Half of PRP will be used for injection with 23-G needle subcutaneously inside and around the periphery of the wound/ulcer, and in the other half, calcium gluconate (0.2 ml, 10%) will be added to form gel sheet PRP, and the result is a platelet gel that sticks to the surface of the wound. The PRP injection and gel dressing was repeated once weekly till a near-complete healing is achieved (<1 cm at the widest/length or breadth), and the patients were followed up for a period of 24 weeks after treatment.

Wounds were photographed before treatment and at each follow-up visit after treatment using a digital camera. The PRP-induced healing is also analyzed microscopically by taking a punch biopsy from three wounds (random selection) at the start day, seventh, and 28th day, and at the end of treatment with maturated coverage.

The control of infection was evaluated with the help of serial pus-culture and sensitivity reports. Pain was measured with Visual Analog Scale for Pain score (VAS) on a scale of 10.

Statistical analysis

Statistics were done by program statistical package for the social sciences (version 20.0; SPSS Inc., Armonk, New York, USA).

Significant level

P value more than 0.05 was considered, nonsignificant, P value less than 0.05, significant, and P value less than 0.001, highly significant.

 Results



A study was performed on 28 patients with nonhealing ulcers of various etiologies. Of them, 19 patients were treated with PRP at weekly intervals for a maximum of seven treatments, and nine patients were treated with saline gauze dressings on alternative days. The age of the patients range from 17 to 56 years and mean ± SD age was 39.68 ± 12.11. Of 19 ulcers in the study group, there were two venous ulcers, nine traumatic ulcers, five pressure ulcers, and three diabetic ulcers [Figure 1]. The duration of the ulcers ranged from 1 month to 12 months, with a mean ± SD of 3.09 ± 3.61 months. The mean ± SD duration of healing of the ulcers was 49.84 ± 22.23 in study group and 108.67 ± 5.64 in the control group (P < 0.001) [Table 1] and [Figure 2],[Figure 3],[Figure 4].{Figure 1}{Table 1}{Figure 2}{Figure 3}{Figure 4}

The mean percentage of improvement in area and volume of the ulcers at day 28, was 44–100% (mean ± SD: 73.32 ± 23.77) in the study group and 17–37% (mean ± SD: 26.89 ± 7.51) in the control group (P < 0.001) [Table 2].{Table 2}

We also noted that there was reduction in pain and discharge within 1 week owing to the anti-inflammatory property of PRP, which contains leukocytes.

Moreover, no adverse effects were reported on the day of treatment and during the patient's follow-up period, deeming this as a safe and effective treatment method for chronic nonhealing ulcers. Furthermore, the overall quality of life of the treated patients improved tremendously after PRP therapy.

 Discussion



Chronic wounds/ulcers come with significant cost and morbidity for the patients and society as a whole. The main goal of any treatment modality is to obtain wound closure expeditiously. The conventional treatment includes adequate debridement, control of infection, revascularization of ischemic tissue, and avoidance of undue pressure on the wound. Skin grafting has shown some efficacy; however, they are not capable of providing the necessary GFs to modulate the healing process and are expensive[10].

In 1986, Knighton et al.[11] showed that the use of autologous platelet factors accelerated epithelialization of granulation tissue leading to complete repair of chronic nonhealing ulcers. This was the first clinical study that demonstrated the promising role of locally acting factors derived from autologous blood in promoting healing of chronic cutaneous ulcers. Platelets contain a large number of GFs and cytokines that play key roles in inflammation and tissue repair, by contributing toward hemostasis at sites of vascular injury. These characteristics of platelets have led to the idea of using PRP as a therapeutic tool to promote wound healing, particularly in patients whose tissue repair is significantly impaired or delayed[12].

PRP enhances wound healing by promoting the healing process secondary to its GFs. These include platelet-derived GF (αα, ββ, and αβ), fibroblast GF, vascular endothelial GF, epidermal GF, insulin-like GF, and transforming GF. These GFs stimulate mesenchymal cell recruitment, proliferation, extracellular matrix degeneration, and cell differentiation for tissue regeneration. These factors are released from α-granule in response to platelet activation by inducers of platelet aggregation[13]. The anti-inflammatory factors in PRP also play a role in wound healing because of the presence of leukocytes, which are at high levels in PRP. In addition to the GFs, platelets release numerous other substances (e.g., fibronectin, vitronectin, and sphingosine 1-phosphate) that are important in wound healing. An advantage of PRP over the use of single recombinant human GF delivery is the release of multiple GFs and differentiation of factors upon platelet activation[14].

There is no standard method of preparation of PRP in literature. Regardless of the rate of centrifugation or the time of centrifugation, a single spin cannot adequately concentrate platelets, because the red blood cells will interfere with their fine separation[4].

In our case series, 19 patients with one wound/ulcer per patient were treated with a single dose of a combination of autologous PRP gel and subcutaneous injections of PRP in and around the wound periphery. All the patients showed healing of the wound with reduction in wound size, and the mean time to healing of the ulcers was 49.84 ± 22.80 days. Reduction in pain was observed in all the patients after treatment, and also, the quality of life of the patients significantly improved. The results demonstrated the safety and efficacy of autologous PRP in treating chronic nonhealing ulcers.

We found that patients who were treated with topical autologous PRP (group A) had a significant reduction in pain, keloids, and hypertrophic scar formation, and they experienced better wound healing after starting PRP in comparison with the control group (group B) (P < 0.0001). None of 19 patients in group A developed adverse events. Other studies similar to our study have concluded that PRP improves the wound healing process[15],[16],[17]. However, in contrast to the results of this study, some authors have shown the failure of PRP in promoting wound healing[18],[19].

One such study was a double-blind randomized and controlled trial which used autologues platelet gel after total knee arthroplasty on 102 patients with a 3-month follow-up. The authors have concluded that there was no positive effect of the autologues platelet gel on wound healing. They have also indicated that it had no effect on pain or hemoglobin values.

Clinical studies regarding the role of PRP in chronic wound healing are increasing in number. Serra et al.[20]compared the effect of platelet-rich gel with 32 patients serving as controls. Healing rates were 96.15% in patients receiving platelet-rich gel against 59.37% in patients not receiving platelet-rich gel.

Martinez-Zapata et al.[21]examined whether autologous PRP promotes the healing of chronic wounds. The median length of treatment was 12 weeks. The authors concluded that the results were nonconclusive as to whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment. Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care, but it is unclear if autologous PRP has an effect on other types of chronic wounds. Three studies reported wound complications such as infection or dermatitis, but results showed no difference in the risk of adverse events in people treated with PRP or standard care. These findings are based on low-quality evidence owing to the small number of studies and patients included, and their poor methodological quality.

Saad Setta et al.[22]investigated the efficiency of PRP on the healing of chronic diabetic ulcers in comparison with PPP (PPP). This study included 24 patients with chronic diabetic ulcers. They were systematically randomized into two groups: PRP group (n = 12) and PPP group (n = 12). The results showed that healing in PRP group was significantly faster. The authors concluded that PRP enhances healing of chronic diabetic foot ulcers. These findings require confirmation in a larger study.

A prospective, randomized, controlled, and blinded multicenter study initially included 35 patients with diabetic foot ulcers who were treated with autologous PRP gel or control (saline gel). Significantly more wounds healed in patients treated with PRP gel [13 (81.3%) of 16 patients] than patients treated with control gel [eight (42.1%) of 19 patients][23].

In our study, PRP group showed 18 of 19 completely healed and one showed improvement in contrast to control group, where three of nine completely healed and six showed improvement.

Ma et al.[24]treated 11 patients with diabetes mellitus (11 wounds) successfully using combined vacuum-assisted closure VAC-PRP therapy. All had been diagnosed with nonhealing wounds based on no obvious granulation tissue on the fifteenth day after primary VAC dressing. No complications were recorded. The mean hospital stay was 49.3 ± 6.2 days. All wounds were completely healed at discharge.

Everts et al.[25]applied platelet-leukocyte gel on 40 patients who underwent open subacromial surgery and showed that the VAS score for pain had been decreased. They also demonstrated a significant reduction in recovery time and analgesic usage during the 6-week follow-up, which were the same as the present study, whereas the mean VAS in the PRP group showed dramatic reduction of pain in contrast to the control group where oral analgesic were prescribed after dressing.

 Conclusion



The results from our case series showed that PRP is a safe and effective treatment modality for chronic nonhealing ulcers. Using PRP to treat chronic wounds/ulcers may not only enhance healing but also improve quality of the resulting scar; moreover, the overall quality of life of the treated patients improved tremendously after PRP therapy.

Randomized prospective clinical trials on larger patient population are necessary to validate the results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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