Comparative efficacy of autologous platelet rich plasma and conventional dressing in the management of chronic ulcers

INTRODUCTION

In era of cutting-edge medical advancements, managing chronic wounds remains a significant challenge.¹ Chronic non-healing ulcers, including venous, arterial, inflammatory, neuropathic, tropical, malignant/traumatic, exhibit prolonged healing time.² These wounds pose significant burden on healthcare systems worldwide.³ Chronic ulcers often remain stalled in healing process due to deficiencies in growth factors (GFs) and cytokines.^4,5 Traditional treatment modalities, while effective in many cases, often fall short in accelerating healing process.⁶ PRP therapy, an emerging therapy, has garnered attention for its potential in regenerative medicine.^7,8 PRP, derived from autologous plasma with concentrated platelets, leverages rich reservoir of GFs inherent in platelets to stimulate tissue regeneration.⁹

Aim

The aim of study was to evaluate the efficacy of autologous PRP therapy in the management of chronic ulcers on lower extremities.

Objectives

Objectives were to determine the effect of autologous PRP therapy on the percentage of surface area reduction/healed on various etiologies of chronic ulcers.

METHODS

Study design

This was a randomized controlled trial conducted at the department of general surgery of M.M. institute of medical sciences and research Mullana (Ambala) from May 1, 2023, to April 30, 2024 after approval from institutional ethics committee (MMIMSR/IEC/2473-30/04/2023). Patients aged 18-80 years of either gender with chronic ulcers were enrolled. Patients were randomly allocated to the PRP group and control group.

Inclusion criteria

Patients aged 18 to 80 years with chronic ulcers of following etiologies were included: venous ulcers, diabetic foot ulcers and traumatic ulcers. The ulcers of 4 weeks duration were included.

Exclusion criteria

Patients with systemic infection, active neoplastic disease, on immunosuppressive therapy for 3 months, on anticoagulant therapy, bedridden, arterial ulcers and hemoglobin concentration less than 10 gm% were excluded. Pregnant or breastfeeding women were excluded. Wound areas over 20 cm² (length×width) were excluded in the study.

PRP group

Once ulcer floor was free of slough and showed healthy granulation, group PRP patients received autologous PRP. PRP was injected into ulcer edge with a disposable syringe followed by a moist saline gauze dressing. Group PRP underwent 3 PRP sessions (days 0, 14 and 28), with final outcome assessed at week 8 (day 56). Between PRP sessions, patients received conventional dressings every 3^rd day, like the control group.

Control group

Once floor of ulcer was free of slough with healthy granulation; control group patients underwent saline-soaked conventional dressing every 3^rd day for 8 weeks.

Autologous PRP preparation

Ten milliliters of autologous blood was drawn and placed in a sodium citrate vacutainer. Using a two-step centrifugation process, the first spin at 1400 rpm for 10 minutes separated the plasma and platelets from red blood cells. The second spin at 2100 rpm for 15 minutes divided the plasma into platelet-poor plasma (PPP) and PRP. PPP was discarded, and PRP was activated with calcium chloride/gluconate (1:9 ratio) just before use. Freshly-prepared PRP was injected immediately to preserve platelet function.

Follow up and outcome assessment

On each planned follow-up visit, the healing of ulcers in both patient groups was assessed by measuring the ulcer's surface area using a sterile scale (maximum length× maximum breadth). The percentage of surface area reduction/healed was calculated with formula: [{(Initial surface area-final ulcer area)/initial surface area}×100]. Other wound characteristics, such as granulation tissue, pain, color, and edges were documented. Study's endpoint was either complete ulcer closure or the end of 56 day follow-up period, whichever came first.

Data analysis

Data was analyzed using SPSS software. Percentage of surface area reduction was compared between 2 groups using t tests, p<0.05 considered statistically significant.

RESULTS

In our study of 60 patients, aged 32 to 78 years, chronic non-healing ulcers were most common in those aged 50-60 years. There was a male preponderance with 82% males (n=49) and 18% females (n=11). Of the participants, 33 were smokers (20 in the PRP group and 13 in the control group), while 27 were non-smokers; which was not a confounding factor.

The mean ulcer duration was 6.9 weeks. The most prevalent ulcer site was the leg (68%, n=41), followed by the foot (25%, n=15) and heel (7%, n=4), (Figure 1).

Venous ulcers were the most common (n=34), followed by diabetic ulcers (n=20) and traumatic ulcers (n=6) (Figure 2).

Ulcer sizes ranged from 5 to 20 cm², with mean sizes of 10.2±3.15 cm² in the control group and 9.46±2.51 cm² in the PRP group. Ulcer surface areas were measured at day 0, 14, 28, and 56. By day 56, the mean ulcer area in the PRP group had decreased to 1.63 cm² (SD=1.82) compared to 4.30 cm² (SD=1.70) in the control group (p<0.0001). The PRP group achieved an 83.78% surface area reduction (%SAR) by day 56, versus 57.78% in the control group (p<0.0001) (Table 2).

Mild adverse effects, such as pain and erythema, were observed in the PRP group, with similar local infection rates in both groups.

DISCUSSION

Chronic wounds are a significant health challenge, especially in developing countries. These wounds often lack essential GFs, making them difficult to heal and prone to infections. Conventional treatments include debridement, infection control, revascularization and minimizing pressure, but they often fall short. Skin grafting is costly and doesn't provide necessary GFs. Topical PRP shows promise by releasing multiple GFs and cytokines, mimicking natural healing.

Studies have shown that PRP significantly accelerates wound healing, with better outcomes in chronic non-healing ulcers compared to traditional treatments. Driver et al observed that significantly more healed diabetic foot ulcers with PRP (81.3%) compared to the control group (42.1%).¹⁰ Anitua et al found that ulcers treated with PRP had a 72.9% wound area reduction and complete healing in some cases, compared to 21.5% in the control group.¹¹ Friese et al demonstrated that PRP treatment led to a higher rate of complete healing and shorter time to heal in diabetic foot ulcers compared to conventional methods.¹²

In our study of 60 patients, those treated with PRP showed greater ulcer area reduction and higher surface area reduction percentage (%SAR) over 56 days. PRP was effective across different ulcer types and had a significant impact on healing rates. Adverse effects were mild and comparable between PRP and control groups. Other studies have corroborated PRP's efficacy in enhancing wound healing, suggesting it as a valuable tool in managing chronic ulcers.

Limitations

The study's sample size was relatively small, and the follow-up period was limited to 42 days, which is insufficient to assess the durability of the treatment effects. Additionally, although the study was randomized, it was open-label, potentially introducing bias. Future studies with larger sample sizes and double-blind designs are needed to confirm these findings.

CONCLUSION

Autologous PRP therapy demonstrates a significantly better outcome in the management of chronic non-healing ulcers compared to conventional dressing methods. Incorporating PRP into treatment protocols may enhance healing outcomes and provide a viable solution for patients suffering from chronic ulcers.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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