Efficacy of autologous platelet-rich fibrin compared to normal saline in the management of chronic venous leg ulcers: A randomized controlled trial

Abstract

Objective

To compare the efficacy of Autologous Platelet-Rich Fibrin (PRF) versus Normal Saline (NS) dressings in healing Chronic Venous Leg Ulcers (CVLUs), focusing on ulcer area reduction and quality of life.

Methods

A randomized controlled trial was conducted at a tertiary care center involving 74 patients with chronic venous leg ulcers (CVLUs). Patients were randomized into two groups: Group A (n = 36) received autologous platelet-rich fibrin (PRF) dressings with four-layer compression therapy, while Group B (n = 38) received Normal Saline (NS) dressings with four-layer compression therapy. Ulcer area and Quality of Life were assessed at baseline and at predefined intervals up to 4 weeks, with continued follow-up for 6 months. The quality of life was assessed using the Charing Cross Venous Ulcer Questionnaire (CCVUQ) and the EuroQol-5 Dimension-5 Level (EQ-5D-5L) scores.

Results

Both groups showed a reduction in ulcer area over time. In the PRF group, mean ulcer area decreased significantly from baseline to 4 weeks (17.46 ± 11.52 cm² to 9.92 ± 8.73 cm²; p = 0.007), whereas the reduction in the saline group was not statistically significant (14.07 ± 14.43 cm² to 11.45 ± 12.02 cm²; p = 0.913). Between-group comparison at 4 weeks was not significant; however, from 4 weeks onward, the PRF group consistently demonstrated smaller mean ulcer areas, with the greatest difference observed at 6 months. CCVUQ and EQ-5D-5L scores improved over time in both groups, with a transient between-group difference favoring PRF at 4 weeks for CCVUQ but no sustained head-to-head superiority in quality-of-life outcomes.

Conclusion

Autologous PRF, when used as an adjunct to standard compression therapy, is associated with earlier and sustained reduction in ulcer area and improvement in ulcer-related Quality-of-Life in patients with chronic venous leg ulcers. No treatment related adverse events were observed during the study period.

Keywords

chronic venous leg ulcer platelet rich fibrin wound healing compression therapy quality of life

Introduction

Chronic Venous Leg Ulcers (CVLUs) are among the most common chronic lower-extremity wounds, affecting approximately 1% of the general population and up to 3% of those over 65 years old.¹ They result from chronic venous insufficiency that leads to sustained venous hypertension in the lower limbs, often due to valvular reflux or post-thrombotic obstruction.² The increased venous pressure initiates a cascade of pathophysiological changes like capillary distention and leakage, leukocyte activation, and inflammation of surrounding tissues. As time progresses, these changes cause skin breakdown, lipodermatosclerosis, and tissue hypoxia, ultimately resulting in ulcer formation around the ankle region.³

CVLUs pose significant clinical challenges. They are typically chronic, slow to heal, and prone to recurrence despite appropriate therapy. Patients often experience persistent pain, discharge, and risk of infection in the ulcer, and the wounds are frequently colonized by bacteria.³ Comorbid conditions such as varicose veins, deep vein thrombosis, obesity, or diabetes can further impede healing. These ulcers substantially impair patients’ quality of life through chronic pain, reduced mobility, and social inconvenience. Severe complications can also arise, including cellulitis, osteomyelitis, or even malignant transformation in long-standing ulcers.² From a healthcare perspective, CVLUs impose a heavy burden as they are resource-intensive to treat over months or years and contribute to high healthcare costs.

Standard care for chronic venous leg ulcers includes evaluation and management of the underlying venous pathology (Open Surgery, Ultrasound-guided or Endovenous techniques), usually in conjunction with sustained compression therapy and appropriate local wound management. However, even with best practices, healing rates of ulcers are variable and recurrence is common, indicating the need for improved therapeutic measures.³ Hence, advanced adjunctive treatments are being explored to enhance healing outcomes for CVLUs.

Autologous platelet-rich fibrin (PRF) in wound healing

Autologous platelet-rich fibrin (PRF) has emerged as a promising biological therapy for enhancing wound healing. PRF is a second-generation platelet concentrate prepared from the patient’s own blood, without the addition of anticoagulants or thrombin. The blood sample is centrifuged to yield a fibrin clot enriched with platelets and leukocytes, which is then used as a membranous dressing or gel. This PRF clot serves as a three-dimensional scaffold that closely mimics the physiological wound-healing matrix. Notably, PRF was initially developed in the field of oral surgery to improve tissue regeneration in dental implants and maxillofacial procedures.⁴ Its success in promoting healing in those fields, led to further investigation of PRF for cutaneous wound healing.

The key advantage of PRF lies in its rich reservoir of growth factors and cytokines sequestered within the fibrin matrix. As the clot gradually resorbs, it releases bioactive factors such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF), among others. These signaling molecules play important roles in wound healing by stimulating angiogenesis, cell proliferation, chemotaxis, and extracellular matrix formation. In addition, the leukocytes embedded in PRF contribute anti-inflammatory and antimicrobial cytokines (e.g., interleukins IL-4, IL-6, IL-10) and release growth factors that promote local immune defense and tissue repair.⁵

The combined effect is a localized, sustained release of healing molecules, signals and a provisional matrix that can accelerate the normal wound-healing process. In vitro, PRF has been shown to markedly stimulate the proliferation of fibroblasts, keratinocytes, and other cell types involved in repair.⁵ Early clinical studies have reported positive outcomes with PRF in treating chronic wounds. For instance, Goda et al. conducted a randomized trial in patients with venous leg ulcers and observed significantly greater ulcer size reduction and faster wound closure in the PRF-treated group compared to those receiving conventional dressings.⁶ Similarly, a recent systematic review of platelet-rich plasma (PRP, a related autologous platelet concentrate) therapies found that all included trials on venous ulcers demonstrated improved healing in patients treated with platelet-rich preparations versus controls.⁷ These findings highlight the potential of PRF as an effective wound healing accelerator. At the same time, the literature notes some variability in preparation methods and outcomes, and most studies to date have been relatively small.⁸ Therefore, while PRF shows promise as a regenerative treatment for chronic ulcers, further high-quality evidence is needed to establish its efficacy and optimal use in CVLUs.

On the other hand, Normal saline cleansing followed by four layered compression bandage therapy represents a conventional and widely used approach in chronic wound management. Normal saline cleansing typically involves cleaning the ulcer area with 0.9% sodium chloride solution and covered by a secondary dry dressing. This simple technique provides a moist healing environment which is known to facilitate cell migration and autolytic debridement of necrotic tissue.⁹

Unlike antiseptics or other solutions, normal saline is isotonic and nontoxic to healing cells, so it cleanses and moistens the ulcer without damaging viable tissue.⁷ Normal Saline is inexpensive, readily available, and easy to apply, making it a staple of standard wound care, especially in resource-limited settings or as a control in clinical studies.

In chronic venous ulcers, after thorough debridement of devitalized tissue, it is common practice to dress the wound with saline-moistened gauze and maintain compression therapy to support venous return.⁷ Despite its regular usage, normal saline has important limitations. Saline alone contains no growth factors, antimicrobials, or other bioactive agents to actively stimulate healing, as it only provides a neutral moist environment. Consequently, healing under normal saline can be slow, as it relies entirely on the body’s inherent repair mechanisms. Frequent dressing changes are often required to keep the wound bed moist, since simple gauze can dry out, adhere to the tissue, and cause pain or trauma upon removal. Studies have shown that while saline wet-to-dry dressings were once the most widely used method, they may actually impede wound healing compared to modern moisture-retentive or bioactive dressings. In one analysis, newer occlusive dressings and advanced wound therapies, although initially more expensive, proved more effective and ultimately cost-saving by accelerating healing and reducing complications.⁹ Nonetheless, Normal saline continues to be employed as a standard baseline treatment and control due to their safety and low cost. In the context of CVLUs, Normal saline with compression is often viewed as the conventional management, against which new therapies can be compared.

Rationale for the present study

Chronic venous leg ulcers (CVLUs) represent a common and challenging manifestation of chronic venous disease, associated with delayed healing, frequent recurrence, and impaired quality of life. Compression therapy remains the cornerstone of management, yet healing outcomes remain variable and many ulcers fail to heal satisfactorily. This has prompted interest in adjunctive therapies that may enhance wound healing when standard care alone is insufficient. Autologous platelet-rich fibrin (PRF) is a biologically active treatment that utilizes autologous platelets and fibrin to deliver growth factors to the wound bed. Early clinical studies have suggested potential benefits of PRF in chronic wound healing. However, the available evidence is limited by small sample sizes, heterogeneity in study design, and a lack of adequately powered comparative trials. Data specifically addressing the role of PRF in venous leg ulcers remain sparse. Consequently, the clinical benefit of PRF over conventional wound dressings has not been clearly established. Robust comparative data are needed to inform clinical practice. This study was therefore designed to evaluate PRF as an adjunct to standard compression therapy in patients with CVLUs.

The primary objective of the present randomized controlled trial was to compare ulcer healing outcomes between PRF dressings and normal saline dressings when used alongside compression therapy. Ulcer size reduction was selected as the principal clinical outcome to objectively assess healing response. In addition, patient-reported quality-of-life measures were incorporated to capture the broader impact of treatment. CVLUs are known to cause pain, restricted mobility, and psychosocial distress, which are not fully reflected by wound measurements alone. Assessment of quality of life therefore represents an important complementary outcome. By combining clinical and patient-centred endpoints, the study aimed to provide a balanced evaluation of treatment effect. The randomized design was chosen to minimize bias and strengthen the level of evidence. Focusing on a single ulcer aetiology and a standardized PRF protocol reduces heterogeneity seen in prior studies. The findings are intended to clarify the role of PRF in the management of CVLUs. Ultimately, the study seeks to support evidence-based decision-making in the treatment of chronic venous leg ulcers.

Methods

The study was carried out in the Department of General Surgery, in collaboration with the Department of Transfusion Medicine, King George Medical University (KGMU), Uttar Pradesh, India which is a tertiary care center equipped with facilities for both wound care and laboratory-based PRF preparation.

The study was started after obtaining Ethical clearance from the Institutional Ethics Committee (Ref code: XXIII-PGTSC-IIA/P53) and after CTRI registration (CTRI/2024/08/072279).

This study was designed as a Randomized Controlled Trial conducted over a period of 4 weeks which was subsequently followed up for 6 months. The objective was to compare the efficacy of Autologous Platelet-Rich Fibrin (PRF) gel dressings versus Normal Saline dressings in the treatment of Chronic Venous Leg Ulcers (CVLUs), with particular focus on ulcer size reduction and quality of life outcomes.

A total of 74 participants from Uttar Pradesh, a state in Northern India, representing a homogeneous regional population diagnosed with chronic venous leg ulcers were enrolled in the study after meeting the inclusion and exclusion criteria. Inclusion Criteria were Chronic venous ulcers of lower extremity for more than 3 months duration and patients giving written informed consent. Exclusion Criteria were participants with ulcer for less than 3 months duration and other causes of chronic ulcers like arterial/neuropathic/diabetic/vasculitic; or with infected ulcers, osteomyelitis affecting the area of the ulcer or ulcers with exposed tendons and bones; participants receiving antiplatelet drugs, anticoagulants or with bleeding diathesis.

All patients underwent Duplex Doppler ultrasonography prior to enrollment, and venous reflux characteristics were systematically documented. Patients with active or recent deep vein thrombosis were excluded during screening, and no participants demonstrated features of post-thrombotic syndrome at baseline. The comorbidities assessed included hypertension, type 2 diabetes mellitus, and obesity, given their recognized impact on impaired wound healing in patients with chronic venous ulcers. Other major systemic comorbidities were uncommon in the study population and were evenly distributed between the two groups.

During this study period, no participants were on additional medications relevant to ulcer healing outside the study protocol. All 74 participants received standardised adjunct medical therapy consisting of oral pentoxifylline 400 mg three times daily and Micronised Purified Flavonoid Fraction (MPFF) 500 mg twice daily, as per institutional practice, and this was identical in both groups. No other systemic medications influencing wound healing were used.

Patients with superficial venous pathology underwent definitive venous intervention prior to study enrollment. Endovenous Laser Ablation (EVLA) was performed for superficial venous disease in eligible patients, with adjunctive Ultrasound-guided Foam Sclerotherapy (UGFS) used for associated perforator incompetence. In patients not treated with EVLA, Catheter-directed Foam Sclerotherapy (CDFS) was employed for superficial venous disease, along with UGFS for perforator incompetence.

Sample size calculation

The sample size was calculated to detect a mean difference of 6 cm² in ulcer area reduction between the groups, assuming a standard deviation of 8.0, α = 0.05, and 90% power. The minimum required sample size was 34 per group. To allow for a 10% attrition rate, a total of 74 patients were recruited (36 in PRF group, 38 in saline group).¹⁰

On the basis of mentioned study,¹¹ the mean changes in size of Ulcer area reduction (Healing progress in between PRP group (0.78 cm²) and Conventional treatment group (2.15 cm²) at 6 months was 1.37 cm and the variance (α²) was 2.01. The sample size (n) = 2 (Ζα + Ζ [ι-β])² × σ/(μι-μ2), assuming 0.05 level of significance (Zα2 = 1.96), and 80% power (Z [ι-β] = 0.84) was 33.75.

n = 2 {(Ζ α / 2 + Ζ [ι - β])}^{2} \times {σ / (μ 1 - μ 2)}^{2}

n = 2 {(1.96 + 0.84)}^{2} \times 2.01 / {(2.15 - 0.78)}^{2}

n = 33.75 (34)

In this study we enrolled a minimum of 34 patients in each group of the study.

Where, n = sample size, Z = Z statistic for a level of confidence, for the level of confidence of 95%, which is conventional, Z value is 1.96, α - level of significance, (1−β) - power, μ - mean difference.

Randomisation

Patients were randomised using computer-generated randomization with allocation concealment via sealed opaque envelopes.

Preparation of platelet rich fibrin

After taking written consent, Venous blood (4 mL per tube, 3 tubes (10 mL)) was collected without anticoagulant into silica-free, plain vacuum tubes (Strivac® plain red-top (silica-free), [Strion Medical Pvt. Ltd, India]). Within 60 seconds of draw, the tubes were centrifuged at 3000 rpm for 15 min using a centrifuge [REMI R-8C] with a rotor radius of r = 10 cm, which corresponds to ∼1006 g (RCF) calculated as RCF (g) = 1.118 × 10^-5 × r × (rpm)². Centrifugation was performed at room temperature ∼22°C. After 15 min, a fibrin gel appeared in the centre of the vacutainer, between the layer of red corpuscles below and acellular plasma above. The obtained PRF was extracted with the help of sterile toothed forceps in a biosafety cabinet and after separating the adhered RBC layer, PRF transferred into a sterile vacutainer (Figures 1–6).

Intervention

Group A: The measurements of the ulcer were taken using clinical photographs and the PRF gel was then placed on the ulcer floor and covered with a sterile gauze piece, which was, in turn, covered with four layer compression bandaging. Compression bandaging was done by the trained personnel in the team. The dressing was removed after 1 week. The PRF remnants were removed with water and sterile gauze and were debrided to remove the slough +/− biofilm. This treatment was repeated every week for 4 weeks.

Group B: The measurement of the ulcer was taken. The ulcer was washed with normal saline and then covered with a sterile gauze followed by four layer compression bandaging. This dressing was left in place for 1 week. This treatment was repeated every week for 4 weeks.

A clinical digital photograph was taken at the start of the study and then at every follow up week which was updated in ImageJ software (as shown in Figure 7) and the area of the ulcer was calculated and documented.

Although digital planimetry is a validated method for wound area measurement, we used standardized digital photographs due to ease of use in a routine outpatient setting, and because prior studies have demonstrated a strong correlation between image-based measurement and planimetry. To minimize distortion, all photographs were taken with the same camera at a fixed distance, with the lens held perpendicular to the wound surface. A standard ruler was included in each frame to allow scale calibration and to correct for any minor lens distortion during digital analysis. In ulcers extending around the gaiter region, photographs were taken from multiple angles and the ulcer outline was approximated on a 2D plane. We acknowledge that this method does not perfectly account for curvature, which may result in a slight underestimation of the true surface area; however, as the same standardized method was applied consistently, relative changes in ulcer size remained valid for comparison.

Statistical analysis

All data were compiled and analyzed using SPSS software version 22. Continuous variables, such as ulcer area and quality-of-life (QoL) scores, were expressed as mean ± standard deviation. Independent t-tests were used to compare means between groups, while repeated-measures ANOVA was applied for within-group comparisons over time. Post-hoc Tukey tests were performed to determine significance between specific time intervals, and a p-value of <0.05 was considered statistically significant.

One patient was excluded from analysis due to protocol-related issues, including failure to meet predefined eligibility criteria identified after enrolment and deviations from the intervention protocol.

Results

Table 1 summarizes the baseline demographic characteristics and comorbidities of patients in the PRF and saline groups. The mean age was comparable between the two groups, with no statistically significant difference observed. All participants in both groups were male and belonged to a homogeneous regional population from Uttar Pradesh, ensuring demographic uniformity. The prevalence of hypertension was low and similar in both groups, while type 2 diabetes mellitus was observed only in a small proportion of patients in the saline group, without a statistically significant difference. Mean Body Mass Index (BMI) was comparable between the groups, with no significant difference detected. Overall, the table demonstrates that both groups were well matched at baseline with respect to key demographic variables and comorbidities.

Table 1.

Baseline demographic characteristics and comorbidities of the study population.

Characteristics	Group A (PRF)(n = 36)	Group B (Saline)(n = 38)	p-value
Demographics
Age (years), mean ± SD	42.14 ± 13.66	40.87 ± 11.79	0.669
Sex, male, n (%)	36 (100)	38 (100)	—
Comorbidities
Hypertension, n (%)	2 (5.56)	2 (5.26)	1.000
Type 2 diabetes mellitus, n (%)	0 (0.0)	3 (7.89)	0.240
Body mass index (kg/m²), mean ± SD	21.99 ± 1.73	22.16 ± 1.35	0.637

p-values were calculated using independent-samples t-test for continuous variables and Fisher’s exact test for categorical variables. All participants were male and from a homogeneous regional population (Uttar Pradesh, North India).

Table 2 summarizes the baseline venous disease characteristics on duplex ultrasonography (venous phase) in both groups. Superficial venous incompetence at the saphenofemoral junction (SFJ) was the most common finding in both Group A (PRF) and Group B (Saline). The distribution of isolated and combined patterns of SFJ, saphenopopliteal junction (SPJ), and perforator incompetence was comparable between the two groups. There was no statistically significant difference in baseline venous duplex characteristics between Group A and Group B.

Table 2.

Baseline venous disease characteristics.

Characteristics on duplex scan (Venous phase)	Group A (PRF)N (%)	Group B (Saline)N (%)	p-value
SFJ incompetence	13 (36%)	16 (42.1%)	0.98
SPJ incompetence	1 (2.7%)	1 (2.6%)	0.98
SFJ and SPJ incompetence	5 (13.8%)	7 (18.4%)	0.98
SFJ with perforator incompetence	6 (16.6%)	6 (15.7%)	0.98
SPJ with perforator incompetence	3 (8.3%)	2 (5.2%)	0.98
SFJ, SPJ and perforator incompetence	6 (16.6%)	4 (10.5%)	0.98
Perforator incompetence	2 (5.5%)	2 (5.2%)	0.98

The overall comparison of categorical Duplex findings between the two groups was performed using the chi-square test of independence and did not demonstrate a statistically significant difference (χ² = 1.19, df = 6, p = 0.98).

Table 3 shows the distribution of surgical procedures performed in the two study groups. Endovenous laser ablation (EVLA), either alone or in combination with ultrasound-guided foam sclerotherapy (UGFS), was the most commonly performed procedure in both groups. The overall distribution of surgical modalities was comparable between Group A (PRF) and Group B (Saline), with no statistically significant difference observed (χ² = 1.46, df = 4, p = 0.83).

Table 3.

Comparison of previous surgeries for venous insufficiency.

Type of surgery	Group A (PRF)N (%)	Group B (Saline)N (%)	p-value
EVLA	15 (41.66)	19 (50.00)	0.83
CDFS	4 (11.11)	5 (13.15)	0.83
UGFS	2 (5.55)	2 (5.26)	0.83
EVLA with UGFS	13 (36.11)	9 (23.68)	0.83
CDFS with UGFS	2 (5.55)	3 (7.89)	0.83

Table 4 presents the comparison of mean ulcer area (in cm²) between Group A (Platelet-Rich Fibrin Gel) and Group B (Normal Saline Dressings) over a 4-week period on a weekly basis and then followed on regular intervals up to 6 months.

Table 4.

Comparison of mean ulcer area (in cm²) between Group A (Platelet-rich fibrin gel) and Group B (Normal saline dressings).

Ulcer area (cm²)	Group A(n = 36)		Group B(n = 38)		t	p-Value
Ulcer area (cm²)	Mean	± SD	Mean	± SD	t	p-Value
Pre-treatment	17.46	11.52	14.07	14.43	1.11	0.269
After 1 week	16.86	10.56	13.73	14.17	1.07	0.287
After 2 weeks	15.27	9.46	13.34	13.37	0.71	0.478
After 3 weeks	12.56	8.72	12.39	12.45	0.07	0.947
After 4 weeks	9.92	8.73	11.45	12.02	−0.62	0.537
After 8 weeks	9.37	8.18	11.27	11.8	−0.8	0.425
After 12 weeks	8.11	7.38	10.76	11.57	−1.17	0.247
After 6 months	5.59	6.06	7.96	9.83	−1.24	0.218

At baseline (pre-treatment), the mean ulcer area was comparable between Group A (17.46 ± 11.52 cm²) and Group B (14.07 ± 14.43 cm²; p = 0.269). Both groups showed progressive ulcer size reduction over time. From week 4 onwards, Group A consistently demonstrated a greater numerical reduction in ulcer area compared to Group B, with mean ulcer area at 12 weeks of 8.11 ± 7.38 cm² in the PRF group versus 10.76 ± 11.57 cm² in the saline group (p = 0.247). At 6-months follow-up, ulcer area was further reduced to 5.59 ± 6.06 cm² in Group A compared to 7.96 ± 9.83 cm² in Group B (p = 0.218).

Table 5 shows on head-to-head comparison using independent-samples t-tests, there was no statistically significant difference in mean ulcer area between the PRF and normal saline dressing groups at baseline or early follow-up. However, from 4 weeks onward, patients treated with PRF consistently exhibited smaller mean ulcer areas compared to those receiving normal saline dressings. The magnitude of this difference increased progressively over time, with the greatest separation observed at 6 months (mean difference −3.70 cm²), indicating a sustained and clinically meaningful advantage of PRF therapy. Although this difference did not reach conventional statistical significance, it demonstrated a clear trend favoring PRF treatment.

Table 5.

Head-to-head comparison of mean ulcer area reduction for each group at each timepoint.

Time point	Group A (PRF)Mean ± SD (cm²)	Group B (Saline)Mean ± SD (cm²)	Mean difference (A−B) (cm²)	p-value
Baseline	17.46 ± 11.52	14.24 ± 14.81	+3.22	0.299
1 week	16.86 ± 10.56	14.08 ± 14.50	+2.78	0.347
2 weeks	15.27 ± 9.46	13.26 ± 13.42	+2.01	0.458
3 weeks	12.56 ± 8.72	11.45 ± 10.51	+1.11	0.622
4 weeks	9.92 ± 8.73	11.93 ± 12.39	−2.01	0.422
8 weeks	9.37 ± 8.18	11.62 ± 12.00	−2.25	0.348
12 weeks	8.11 ± 7.38	10.97 ± 11.78	−2.86	0.213
6 months	5.59 ± 6.06	9.29 ± 11.13	−3.70	0.079

Table 6 compares the mean CCVUQ scores between Group A (Platelet-Rich Fibrin Gel) and Group B (Normal Saline Dressings) over a 4-week period on a weekly basis and then followed on regular intervals up to 6 months to assess quality of life (QoL) changes in chronic venous leg ulcer patients.

Table 6.

Comparison of mean CCVUQ scores between Group A (Platelet-rich fibrin gel) and Group B (Normal saline dressings).

CCVUQ score	Group A(n = 36)		Group B(n = 38)		t	p-Value
CCVUQ score	Mean	± SD	Mean	± SD	t	p-Value
Pre-treatment	63.64	8.67	62.97	9.84	0.31	0.759
After 1 week	63.36	8.01	63.63	8.36	−0.14	0.888
After 2 weeks	63.53	7.66	62.37	6.78	0.69	0.492
After 3 weeks	61.25	4.96	63.66	5.97	−1.88	0.064
After 4 weeks	59.22	6.68	67.00	6.60	−5.04	<0.001
After 8 weeks	62.58	5.46	63.18	5.52	−0.47	0.639
After 12 weeks	62.5	5.42	63.5	5.54	−0.78	0.435
After 6 months	61.75	3.81	63.87	3.78	−2.4	0.019

Quality of life, assessed using the CCVUQ score, was similar in both groups at the start of the study, with mean scores of 63.64 ± 8.67 in the PRF group and 62.97 ± 9.84 in the normal saline group (p = 0.759). During the first 2 weeks, there was no noticeable difference between the groups. From the third week onward, patients treated with PRF dressings began to report better quality of life. This improvement became clearly significant at 4 weeks, where the PRF group had lower (better) CCVUQ scores compared to the saline group (59.22 ± 6.68 vs 66.58 ± 6.28; p < 0.001). Although the differences during the mid-follow-up period were not statistically significant, the PRF group consistently showed better scores. At 6 months, this improvement was again statistically significant, with the PRF group reporting better quality of life than the saline group (61.75 ± 3.81 vs 63.87 ± 3.78; p = 0.019).

Table 7 presents the head-to-head comparison of CCVUQ scores between the PRF and saline groups at predefined follow-up intervals. Baseline CCVUQ scores were comparable between the two groups, indicating similar ulcer-specific quality of life at study entry. No statistically significant between-group differences were observed at 1, 2, or 3 weeks of follow-up. At 4 weeks, the PRF group demonstrated a significantly lower CCVUQ score compared with the saline group, reflecting a greater improvement in ulcer-related quality of life at this time point. However, this between-group difference was not consistently maintained at subsequent follow-up visits, including 8 weeks, 12 weeks, and 6 months. Overall, these findings suggest an early improvement in ulcer-specific quality of life with PRF treatment, without sustained long-term superiority over saline dressings.

Table 7.

Head-to-head comparison of CCVUQ scores for each group at each time point.

Time point	Group A (PRF)Mean ± SD (cm²)	Group B (Saline)Mean ± SD (cm²)	Mean difference (A−B) (cm²)	p-value
Baseline	63.64 ± 8.67	63.36 ± 9.96	0.28	0.21
1 week	63.36 ± 8.01	63.00 ± 8.38	0.36	0.84
2 weeks	63.53 ± 7.66	63.00 ± 6.74	0.53	0.72
3 weeks	61.25 ± 4.96	62.58 ± 6.38	−1.33	0.33
4 weeks	59.22 ± 6.68	66.72 ± 6.14	−7.50	<0.001
8 weeks	62.58 ± 5.46	62.64 ± 5.81	−0.06	0.96
12 weeks	62.50 ± 5.42	62.08 ± 5.84	0.42	0.74
6 months	61.75 ± 3.81	63.17 ± 5.17	−1.42	0.18

Table 8 compares the mean EQ-5D-5L scores between Group A (Platelet-Rich Fibrin Gel) and Group B (Normal Saline Dressings) over a 4-week period on a weekly basis and then followed on regular intervals up to 6 months to assess health-related quality of life.

Table 8.

Comparison of mean EQ-5D-5L scores between Group A (Platelet-rich fibrin gel) and Group B (Normal saline dressings).

5Q 5D 5L score	Group A (n = 36)		Group B (n = 38)		t	p-Value
5Q 5D 5L score	Mean	± SD	Mean	± SD	t	p-Value
Pre-treatment	65.00	8.28	63.95	10.54	0.48	0.635
After 1 week	64.86	8.49	65.39	8.49	−0.27	0.788
After 2 weeks	64.86	8.98	65.00	10.07	−0.06	0.950
After 3 weeks	67.08	8.89	67.63	8.03	−0.28	0.781
After 4 weeks	70.00	9.78	69.74	8.62	0.12	0.902
After 8 weeks	68.75	8.57	65.66	7.55	1.65	0.103
After 12 weeks	69.72	9.63	64.08	6.86	2.91	0.005
After 6 months	69.17	8.74	65.92	7.52	1.71	0.091

Health-related quality of life assessed using the EQ-5D-5L score showed no significant difference between the two groups during the early follow-up period. At 1, 2, and 3 weeks, the mean scores were comparable between the PRF group and the normal saline group (p > 0.05). From the 4th week onward, patients in the PRF group demonstrated a gradual improvement in EQ-5D-5L scores compared to those receiving saline dressings. This difference became statistically significant at 12 weeks (69.72 ± 9.63 vs 64.08 ± 6.86; p = 0.005). At the 6-months follow-up, the PRF group continued to have better quality-of-life scores, although the difference was not statistically significant (p = 0.091).

Table 9 summarises the head-to-head comparison of EQ-5D-5L scores between the PRF and saline groups across the study period. At baseline, the PRF group demonstrated a significantly higher EQ-5D-5L score compared with the saline group, indicating a baseline difference in health-related quality of life. No statistically significant between-group differences were observed at 1, 2, or 3 weeks of follow-up. Although EQ-5D-5L scores were numerically higher in the PRF group at later time points, including 4 weeks, 8 weeks, 12 weeks, and 6 months, these differences did not consistently reach statistical significance. Both groups demonstrated improvement in EQ-5D-5L scores over time. Overall, the findings suggest comparable long-term health-related quality-of-life outcomes between the two treatment groups.

Table 9.

Head-to-head comparison of EQ-5D-5L scores for each group at each time point.

Time point	Group A (PRF)Mean ± SD (cm²)	Group B (Saline)Mean ± SD (cm²)	Mean difference (A−B) (cm²)	p-value
Baseline	65.00 ± 8.28	63.89 ± 10.76	+1.11	0.04
1 week	64.86 ± 8.49	65.00 ± 8.62	−0.14	>0.05
2 weeks	64.86 ± 8.98	64.86 ± 9.96	0.00	>0.05
3 weeks	67.08 ± 8.89	67.22 ± 8.40	−0.14	>0.05
4 weeks	70.00 ± 9.78	69.31 ± 8.46	+0.69	>0.05
8 weeks	69.17 ± 8.98	64.17 ± 6.49	+5.00	>0.05
12 weeks	69.17 ± 8.74	64.44 ± 7.63	+4.73	>0.05
6 months	72.78 ± 9.06	68.33 ± 7.27	+4.45	>0.05

The following serial clinical photographs of three distinct patients demonstrate a progressive reduction in ulcer dimensions over a four-week period following treatment with platelet-rich fibrin (PRF) dressings in conjunction with standardized four-layer compression therapy (Figures 8–10).

Discussion

Chronic venous leg ulcers are a major public health problem, especially among the elderly, due to their long duration, frequent recurrence, and negative impact on quality of life. Conventional management, often effective in a subset of patients, is limited by slow healing, high treatment burden, and inadequate response in chronic or large ulcers.⁹ This randomized controlled trial evaluated the efficacy of autologous platelet-rich fibrin (PRF) gel dressing as an adjunct to standard four-layer compression therapy, compared to the conventional approach of normal saline dressing with compression, in patients with CVLUs.

The efficacy of PRF and similar platelet-rich therapies in the management of chronic venous leg ulcers is well-documented and consistently positive across the literature. The randomized controlled trial by Somani and Rai (2017)¹² directly compares PRF to saline dressings, concluding that the PRF group showed a significantly higher percentage of wound area reduction and a shorter time to complete healing. This seminal study provides a direct and powerful benchmark for the current research, validating the use of PRF as a superior treatment modality.

Cardenosa, Dominguez-Maldonado, and Cordoba-Fernandez (2017)¹³ further reinforce the findings on platelet-rich plasma (PRP), a closely related therapy. Their study emphasizes not only the efficacy but also the safety of platelet-based treatments. They highlight how PRP, by releasing a concentrated cocktail of growth factors, accelerates tissue regeneration and wound closure. This finding is crucial as it substantiates the biological basis for the observed clinical improvements, linking the macroscopic healing to the microscopic action of growth factors.

The research by Goda (2018)⁶ on autogenous leucocyte-rich and platelet-rich fibrin (L-PRF) also supports the current study’s findings. Goda’s randomized controlled study demonstrates that L-PRF is effective in treating venous ulcers, providing another layer of evidence for the therapeutic value of PRF. This study is particularly valuable as it uses a similar formulation to PRF, adding to the body of evidence that supports the use of these advanced dressings.

Similarly, Moneib et al. (2018)¹⁴ compared autologous platelet-rich plasma to conventional therapy, concluding that PRP led to significantly better outcomes in terms of wound healing. Their study further validates the effectiveness of these therapies, showing that platelet-rich plasma, whether in a gel, fibrin, or liquid form, consistently outperforms traditional dressings. The collective findings of these studies (Somani, Cardenosa, Goda, and Moneib) establish a clear and consistent pattern of superior efficacy.

While not specific to venous ulcers, the study by Elsaid et al. (2020)¹⁵ on non-healing diabetic foot ulcers is highly relevant. Their randomized controlled trial on autologous PRP versus saline dressing found that PRP significantly improved healing rates. This broader application demonstrates the generalizability of platelet-based therapies for chronic, non-healing wounds, suggesting that the mechanisms of action are effective regardless of the underlying pathology (venous insufficiency or diabetes), thereby strengthening the argument for the use of PRF in chronic ulcers.

The study by Elgarhy et al. (2020)¹¹ provides a useful comparison between two different forms of platelet therapy—topical platelet gel and PRP injection—in the treatment of venous leg ulcers. This research adds a new dimension to the discussion by exploring different methods of application while still affirming the overall efficacy of platelet products. The fact that both forms were effective underscores the power of the platelets themselves and the growth factors they contain.

Helmy et al. (2021)¹⁶ in a large randomized controlled trial on 80 patients, provided a robust, objective assessment of PRP’s potential for treating chronic venous ulcers. Their study’s strong statistical findings and larger sample size provide a more definitive confirmation of the effectiveness of platelet therapies. This study is particularly important for the current thesis as it offers compelling, recent evidence that aligns with the thesis’s core hypothesis.

Finally, the foundational work of O'Connell et al. (2006)¹⁷ on autologous platelet-rich fibrin matrix as a stimulator of healing provides the historical and mechanistic basis for all subsequent research. Their study established that the fibrin matrix acts as a scaffold for new tissue growth, and the sustained release of growth factors from this matrix is what drives the healing process. This early research is essential for providing the biological explanation that underpins all the positive clinical outcomes observed in the more recent trials, tying all the findings together and providing a comprehensive understanding of why PRF is so effective.

This study demonstrates a significant improvement in ulcer healing among patients treated with autologous Platelet-Rich Fibrin (PRF) gel dressings compared to those receiving conventional saline dressings. The PRF group showed a marked reduction in ulcer size, particularly in the third and fourth weeks. These factors play essential roles in promoting angiogenesis, fibroblast proliferation, matrix remodeling, and epithelial repair, all of which are critical to wound healing. In contrast, the control group showed only modest and statistically insignificant ulcer size reduction, underscoring the limited regenerative potential of saline dressings. This biological activity of PRF, beyond mere moisture retention, contributes meaningfully to tissue repair in chronic wounds. The findings are consistent with prior studies and further strengthened by this study’s larger sample size, objective ulcer measurement, and structured comparison. The limitations of the study were the lack of blinding, use of photographic measurement of ulcer, rate of complete healing and recurrences was not included in the study.

Beyond clinical healing, PRF significantly improved patient-reported outcomes. Quality of life assessed using the Charing Cross Venous Ulcer Questionnaire improved in the PRF group but worsened in the control group, with the difference being statistically significant at 4 weeks. While EQ-5D-5 L scores improved slightly in both groups, the results were not statistically significant, likely due to the tool’s general nature and the short follow-up period. Importantly, no adverse events were reported, reaffirming PRF’s safety. As a cost-effective, autologous, and easy-to-use therapy, PRF holds great promise for integration into routine wound care, especially in resource-limited settings. However, limitations such as short follow-up, moderate sample size, and lack of blinding suggest that longer-term, multicenter studies are needed. Standardizing PRF preparation protocols and comparing it with other advanced therapies will help better define its role in chronic wound management.

Conclusion

Chronic venous leg ulcers remain a persistent clinical challenge due to delayed healing and recurrence. This study evaluated the effectiveness of autologous platelet-rich fibrin (PRF) versus normal saline dressings, both with compression therapy. PRF significantly reduced ulcer size over 4 weeks, showing clear superiority over saline dressings.

PRF gel dressings were associated with significant within-group reduction in ulcer area and improved ulcer-related quality of life within 4 weeks. However, the between-group comparison did not demonstrate statistical superiority over saline dressings. PRF may therefore be considered a promising adjunct, but further multicenter studies with larger cohorts and longer follow-up are required.

Supplemental material

Supplemental Material - Efficacy of autologous platelet-rich fibrin compared to normal saline in the management of chronic venous leg ulcers: A randomized controlled trial

Supplemental Material for Efficacy of autologous platelet-rich fibrin compared to normal saline in the management of chronic venous leg ulcers: A randomized controlled trial by Pallaprolu Jyothirmai, Jitendra Kumar Kushwaha, Saumya Singh, Shailendra Yadav, Tulika Chandra, Krishna Kant Singh, Abhinav Arun Sonkar in Phlebology

Footnotes

Acknowledgments

We acknowledge the support of the Department of General Surgery and Department of Transfusion Medicine, King George’s Medical University, Lucknow, Uttar Pradesh (U.P.), India as well as all the study participants for their consent and co-operation during the entire study process. I would like to thank Prof. Jitendra Kumar Kushwaha, for his assistance and guidance in this research.

ORCID iD

Pallaprolu Jyothirmai

Ethical consideration

Approved by Institutional Ethics Committee, King George’s Medical University (Ref code: XXIII-PGTSC-IIA/P53).

Author contributions

Dr. Pallaprolu Jyothirmai - Patient recruitment (after consent) from OPD (Out Patient Department), collection of venous blood samples, preparation of Platelet Rich Fibrin (PRF), application of PRF and follow up with ulcer size measurement and assessing Questionnaire on a weekly basis.

Prof. Jitendra Kumar Kushwaha - Researched the literature and conceived the study, Guidance at each and every step and providing suggestions for improvement of standard, Supervision.

Dr. Saumya Singh - Guidance in obtaining Ethical approval, Resource management, Supervision.

Dr. Tulika Chandra - Guidance and Supervision regarding collection of blood samples and process of centrifugation, extraction of Platelet Rich Fibrin (PRF) under aseptic conditions, reviewing the progression and monitoring on a regular basis.

Prof. Shailendra Kumar Yadav - Guidance in selection of patients, Reviewing the entire process on a regular basis and monitoring the results.

Prof. K.K. Singh - Reviewing the process and guidance at required level and timely updating the study.

Dr. Abhinav Arun Sonkar - Guidance and supervision at every step and closely monitoring the entire process.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Clinical trial registration

Clinical Trials Registry - India (CTRI); Registration Number: CTRI/2024/08/072279; URL:

Guarantor

Dr. Pallaprolu Jyothirmai (jyothirmai258@gmail.com).

Supplemental material

Supplemental material for this article is available online.

References

Xie

Rerkasem

, et al. The venous ulcer continues to be a clinical challenge: an update. Burns Trauma 2018; 6: 18. https://doi.org/10.1186/s41038-018-0119-y

Bonkemeyer

Gan

Townsend

. Venous ulcers: diagnosis and treatment. Am Fam Physician 2019; 100(5): 298–305.

Singampalli

Rajan

YRD

Hemanth Rathod

, et al. The efficacy of platelet-rich fibrin in the management of chronic nonhealing ulcers of the lower limb. Cureus 2022; 14(7): e26829. https://doi.org/10.7759/cureus.26829

Chandran

Sivadas

. Platelet-rich fibrin: its role in periodontal regeneration. Saudi J Dent Res 2014; 5(2): 117–122. https://doi.org/10.1016/j.ksujds.2013.09.001

Salgado-Pacheco

Serra-Mas

Otero-Viñas

. Platelet-rich plasma therapy for chronic cutaneous wounds stratified by etiology: a systematic review of randomized clinical trials. Drugs Ther Perspect 2024; 40: 31–42. https://doi.org/10.1007/s40267-023-01044-7

Goda

AAMD

. Autogenous leucocyte-rich and platelet-rich fibrin for the treatment of leg venous ulcer: a randomized control study. The Egyptian Journal of Surgery 2018; 37(3): 316–321. https://doi.org/10.4103/1110-1121.239205

Daley

. Wound care treatment & management. Medscape, 2020. https://www.medscape.com/viewarticle/194018_3 (Accessed 20 Mar. 2025).

Yuvasri

Rai

. Comparison of efficacy of autologous platelet-rich fibrin versus Unna’s paste dressing in chronic venous leg ulcers: a comparative study. Indian Dermatol Online J 2020; 11(1): 58–61. https://doi.org/10.4103/idoj.IDOJ_119_19

Lee

Kandula

Sherber

. Beyond wet-to-dry: a rational approach to treating chronic wounds. Eplasty 2009; 9: e14.

10.

Franks

Barker

Collier

, et al. Management of patients with venous leg ulcers: Challenges and current best practice. J Wound Care 2016; 25(Suppl 6): S1–S67. https://doi.org/10.12968/jowc.2016.25.Sup6.S1

11.

Elgarhy

El-Ashmawy

Bedeer

, et al. Evaluation of safety and efficacy of autologous topical platelet gel vs platelet rich plasma injection in the treatment of venous leg ulcers: a randomized case control study. Dermatol Ther 2020; 33: el3897. https://doi.org/10.1111/dth.13897

12.

Somani

Rai

. Comparison of efficacy of autologous platelet-rich fibrin versus saline dressing in chronic venous leg ulcers: a randomised controlled trial. J Cutan Aesthet Surg 2017; 10(1): 8–12. https://doi.org/10.4103/JCAS.JCAS_137_16

13.

Cardeñosa

Dominguez-Maldonado

Córdoba-Fernández

. Efficacy and safety of the use of platelet-rich plasma to manage venous ulcers. J Tissue Viability 2017; 26: 138–143. https://doi.org/10.1016/j.jtv.2016.11.003

14.

Moneib

Youssef

Aly

, et al. Autologous platelet-rich plasma versus conventional therapy for the treatment of chronic venous leg ulcers: a comparative study. J Cosmet Dermatol 2018; 17(3): 495–501. https://doi.org/10.1111/jocd.12401

15.

Elsaid

El-Said

Emile

, et al. Randomized controlled trial on autologous platelet-rich plasma versus saline dressing in treatment of non-healing diabetic foot ulcers. World J Surg 2020; 44: 1294–1301. https://doi.org/10.1007/s00268-019-05316-0

16.

Helmy

Farouk

Ali

, et al. Objective assessment of Platelet-Rich Plasma (PRP) potentiality in the treatment of Chronic leg Ulcer: RCT on 80 patients with Venous ulcer. J Cosmet Dermatol 2021; 20(10): 3257–3263. https://doi.org/10.1111/jocd.14138

17.

O’Connell

Impeduglia

Hessler

, et al. Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers. Wound Repair Regen 2008; 16(6): 749–756. https://doi.org/10.1111/j.1524-475X.2008.00426.x