Platelet‐Rich Plasma in a Refractory Venous Leg Ulcer Following Multiple Failed Skin Grafts

ABSTRACT

Chronic lower‐extremity ulcers remain a major therapeutic challenge. Conventional treatments—including compression therapy, debridement, dressings, antibiotics, pharmacologic agents, hyperbaric oxygen, and skin grafting—frequently fail to provide durable closure, largely due to limited modulation of the wound‐healing cascade. Autologous platelet‐rich plasma (PRP) is gaining interest as a regenerative adjunct capable of delivering concentrated endogenous growth factors. We report a 58‐year‐old woman with more than 20 previous skin grafting procedures for recurrent lower‐leg ulcers, arising from self‐inflicted trauma and secondary infections. Multidisciplinary care of a 15 cm × 18 cm ulcer incorporating debridement, targeted antibiotics, and mainly PRP, administered in six sessions, contributed substantially to ulcer reduction and finally to complete wound healing. PRP has shown promise in enhancing wound closure rates, healing time, and tissue quality. However, the absence of standardized protocols for preparation, dosing, and application, as well as inconsistent outcome reporting, limits its broader adoption. This case underscores the potential role of PRP as a central component in managing complex, refractory ulcers, particularly when behavioural and infectious factors impede healing. Standardized protocols and robust clinical trials are warranted to clarify its role in chronic wound care.

Highlights

• PRP has shown promise in enhancing wound closure rates, and tissue quality.

• This case underscores the potential role of PRP as a central component in managing complex, refractory ulcers, particularly when behavioral and infectious factors impede healing.

• Standardized protocols and robust clinical trials are warranted to clarify PRP role in chronic wound care.

1. Introduction

Chronic ulcers are skin lesions that fail to heal within a typical timeframe, take unusually long to close, or show a tendency to recur [1, 2]. Venous ulcers are the most prevalent subtype affecting the lower extremities and are associated with substantial morbidity and impaired quality of life [1]. Despite the widespread use of conventional modalities, including compression therapy (the standard of care for venous ulcers), surgical or mechanical debridement, occlusive dressings, topical or systemic antibiotics for infected wounds, pharmacologic therapies, hyperbaric oxygen, and even skin grafting, clinical outcomes are frequently suboptimal [3, 4, 5, 6].

In recent years, several regenerative medicine strategies have been investigated for the treatment of refractory leg ulcers. These include dermal substitutes and bioengineered skin equivalents, autologous platelet‐rich plasma (PRP), stromal vascular fraction cells (SVFs) derived from adipose tissue, peripheral blood mononuclear cells (PBMCs), and energy‐based therapies such as laser treatment. These approaches aim to enhance angiogenesis, modulate inflammation, stimulate cellular proliferation, and promote extracellular matrix remodelling in wounds that have failed to respond to conventional management [5, 7, 8, 9]. Although encouraging results have been reported, evidence remains heterogeneous, and no single regenerative modality has emerged as the definitive standard for difficult‐to‐heal venous ulcers. Consequently, further clinical experience and comparative studies are required to define their optimal indications and long‐term effectiveness.

In this setting, autologous PRP has emerged as a promising adjunct or alternative therapy [5]. PRP provides a concentrated source of endogenous growth factors and has already shown regenerative benefits in oral and maxillofacial procedures, supporting its potential role in chronic wound healing [1]. Moreover, as an autologous, biocompatible modality that is comparatively simple and cost‐conscious, PRP has shown a favourable safety profile with reported clinical benefits in chronic ulcer management [3]. It concentrates multiple growth factors (such as vascular endothelial growth factor and epidermal growth factor) that act synergistically to promote angiogenesis, tissue regeneration, and nerve repair, potentially accelerating wound closure [10]. Beyond its regenerative profile, PRP may exhibit antibacterial activity against Staphylococcus aureus , supporting infection control and wound integrity [10]. PRP shows encouraging results, especially in lower‐extremity venous ulcers, by accelerating closure, shortening healing time, and improving outcomes across chronic ulcer types, warranting further real‐world evaluation [2, 8, 11].

This case, reported in accordance with the SCARE guidelines, illustrates the use of autologous PRP in the management of a refractory venous leg ulcer, highlighting its potential applicability in clinical settings.

1.1. Ethical Considerations

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent for publication of clinical details and accompanying images was obtained from the patient. Our institution does not require ethical approval for individual case reports.

2. Case Presentation

A 58‐year‐old woman with a long history of psychiatric illness presented over the last 10 years with multiple recurrent ulcers of both lower legs secondary to mild venous insufficiency and self‐inflicted trauma, leading to repeated infections. In that period, she underwent over 20 sessions of surgical debridement and split‐ and full‐thickness skin grafting procedures at our institution, with long hospitalizations. Negative‐pressure wound therapy was also applied on several occasions before and/or after the surgery to optimize the recipient bed. The lesions originated as superficial self‐induced injuries that progressed to deeper ulcerations, compounded by secondary infections involving organisms such as Staphylococcus aureus, Enterobacter faecalis, Escherichia coli, and Pseudomonas aeruginosa . Although graft intake was initially complete, a typical pattern of gradual healing deterioration at home, due to non‐adherence to postoperative wound care instructions and further self‐trauma, was observed.

In the last episode, an infected ulcer of the anteromedial lower leg, measuring 15 cm × 18 cm, and expanding posteriorly and laterally up to the lateral malleolus was visible (Figure 1A,B). Peripheral vascular status was stable, and diabetes, vasculitis, or other causes of insufficient blood supply locally were excluded.

FIGURE 1.

Venous leg ulcer, at the last admission (A) the left medial knee, (B) it continues posteriorly to the left lateral knee, (C) at 2 months, following four PRP sessions, only a smaller ulcer of the medial knee remained (D) at 4 months, following six PRP sessions, complete ulcer closure.

A multidisciplinary management plan was implemented, involving plastic surgery, psychiatry, and infectious disease specialists. Necrotic areas were sharply debrided, and culture‐based antibiotics were administered. Traditional topical wound management with dressings and compression was then applied until the infection signs were diminished.

At 2 weeks, PRP sessions (single centrifugation at 4000 rpm for 5 min) were incorporated in the treatment plan, with two sessions with 1 week interval, followed by a similar pattern of two sessions after every 3 weeks, for a total of six sessions (Figure 1C,D). Autologous PRP was prepared within the Department of Plastic Surgery according to the institution's standardized protocol for PRP preparation and handling of autologous blood products. According to local institutional practice, preparation by or approval from the Transfusion Medicine Service was not required. The wound showed a rapid healing progression, which was continually improved until the complete wound closure after 4 months. A pliable skin and soft tissue development was also encountered, compared to the previous skin grafting sessions with intense scarring. The patient also adhered to psychiatric support and wound care protocols, with family involvement.

3. Discussion

This case illustrates an exceptionally challenging, behaviourally mediated pattern of chronic ulceration. A patient with longstanding psychiatric comorbidity experienced recurrent infected lower‐limb ulcers that persisted despite multiple successful grafts, with relapses driven by self‐inflicted trauma and inconsistent postoperative wound care. In this refractory clinical setting, autologous PRP administered as monotherapy (three pairs of sessions at three‐week intervals) resulted in substantial reduction of the index ulcer, indicating that PRP may be effective even when conventional modalities are undermined by patient‐related risk factors.

Specific criteria—such as age ≥ 80 years with chronic VLU of at least 6 weeks' duration [1] and < 50% healing over the preceding period [4]—have been adopted as inclusion criteria in previous studies. In our case, however, unlike several earlier reports, local infection was not an exclusion criterion, as wound cultures revealed colonization of the affected site by several bacteria [4]. This is important, as we are dealing with a complicated, poorly healing ulcer with a profoundly impaired reparative response and a wound bed rendered highly hostile by dense scar tissue and recurrent bacterial colonization.

A recent meta‐analysis of 16 RCTs found that PRP significantly increases complete healing of venous ulcers, reduces ulcer size, and shortens time to closure versus conventional care, while not increasing infections or irritative dermatitis and lowering recurrence rates [5]. Taken together with our case, these findings support a treatment model in which PRP offers clear practical advantages for chronic, hard‐to‐heal venous ulcers. Our case highlights clinical scenarios where PRP may be particularly valuable: (i) recurrence‐prone ulcers, (ii) ulcers complicated by persistent local bacterial colonization or a hostile, scarred wound bed, (iii) behaviourally mediated or non‐compliant patients in whom conventional modalities are repeatedly “undone,” and (iv) fragile patients in whom further surgery is undesirable. In such settings, PRP can function as a problem‐solving, standalone option that restores progress toward closure.

Overall, this case exemplifies the efficacy of PRP in managing refractory chronic ulcers in terms of complete healing, tissue quality, and time reduction.

The present case should also be interpreted in the context of other regenerative strategies currently available for chronic wound management. Dermal substitutes and bioengineered skin constructs have demonstrated improved healing rates in selected venous ulcers but are associated with increased costs and may require multiple procedures [7, 8, 12]. Cell‐based therapies, including SVFs and PBMCs, have shown promising proangiogenic and regenerative effects in preliminary studies [13, 14, 15]; however, their use remains limited by procedural complexity, regulatory considerations, and the lack of large‐scale evidence. Similarly, laser‐based therapies have been investigated as adjunctive modalities with variable outcomes [9, 16]. Compared with these approaches, PRP offers several practical advantages, including autologous origin, ease of preparation, favourable safety profile, and relatively low cost. Both activated and non‐activated PRP preparations have been investigated in chronic wound management, with studies reporting favourable healing outcomes for each approach; however, current evidence remains insufficient to establish the superiority of one preparation method over the other, and no consensus has yet been reached regarding the optimal PRP protocol for venous leg ulcers [17]. In our patient, who had undergone more than 20 previous skin‐grafting procedures without durable success, serial PRP applications were associated with progressive wound reduction and eventual complete healing, supporting its potential value as a salvage option in highly refractory cases.

PRP shows a generally reassuring safety profile without increased adverse events [5]. However, the evidence base in chronic venous leg ulcers, remains constrained by procedural heterogeneity, inconsistent product characterization, inadequate standardization and regulation, short follow‐up, and underpowered studies [1, 3, 10, 11]. Preparation techniques, dosing intervals, and application methods vary widely, and reporting is inconsistent [11]. Accordingly, large, robust randomized trials comparing PRP to conventional care are needed to specifically evaluate lower‐extremity venous ulcers and to standardize PRP preparation, dosing, delivery, and outcome reporting (e.g., complete healing, ulcer dimensions, time to closure), with explicit descriptions of processing and use to ensure comparability [5, 10, 11, 18]. In summary, this case illustrates the complexity of managing chronic lower‐extremity ulcers and underscores the role of PRP along with surgical and other conventional strategies.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.