PracticalDermatology

Mohs surgery is a technique employed by dermatologic surgeons to progressively remove skin cancers in a conservative manner until only cancer-free tissue remains, thus allowing one to be “tissue sparing” in the process and have 100 percent margin control. This procedure is widely used when dealing with specific anatomical locations, such as the face, cancers with aggressive pathology, or cancers that are large or recurrent in nature. After removal of a skin cancer, closure is required to maintain normal function and cosmesis of the skin. Although most closures are achieved via primary intent (suturing), this may not be practical for numerous reasons including: anatomical location (lower extremities, ears, nose, and wherever concavities are present), defect size, excessive tensile strength caused by primary closure, patient populations that may have multiple medical comorbidities, patients on anticoagulant therapy in whom closure may cause significant morbidity, and social factors, such as patients being unable to care for complicated closures. Therefore healing by second intent for surgical wounds may become a viable option for Mohs surgeons.¹

Issues that patients may encounter during wound healing by second intent include: a halt in tissue granulation or re-epithelialization, contracture formation, prolonged healing time, and heightened risk of infection. All these factors can lead to the development of a chronic non-healing wound post-op, thus resulting in increased morbidity and medical expenses for both patients and society. Efforts to improve clinical outcomes for chronic wound treatment have led to the development of growth factor-based therapies.^1,2 One such approach to chronic wound care is the use of autologous platelet-rich plasma (PRP) to promote wound healing.³

Autologous PRP is plasma that has been taken directly from a patient with a chronic wound and spun down to concentrate just that patient’s platelets, cytokines, chemokines, and growth factors.^3-5 The rationale for using autologous PRP over other standardized treatment regimens is that it actively stimulates wound healing/closure by initiating the clotting cascade and release of multiple growth factors (Figure 1) precisely at the wound site where these factors are most needed.

Figure 1. PRP Growth Factors³

Some of these factors are only released within a healing wound during specific phases of the inflammatory cascade and not long enough for their full therapeutic potential to be realized. Others don’t even get released in all types of wounds and may only make an appearance during an infectious process or other specific bodily/environmental insult.^5-7 Furthermore, the risk of adverse events due to autologous PRP as compared to other artificial wound healing modalities seems to be decreased as a patient’s own biological material is being used to stimulate their recovery rather than the material of a foreign substance.⁵

The process of utilizing autologous PRP for wound healing is relatively straightforward and consists of obtaining a small sample of fresh whole blood from a patient, isolating and concentrating the autologous PRP from this sample via centrifugation with a separating gel, and then reinserting this newly concentrated PRP back into the patient at the site of the wound.⁸

Currently, PRP’s value and utility in both clinical therapy and the cosmetics industry is still being assessed.⁹ Although the effectiveness of PRP as an antibacterial and regenerative agent in wound healing trajectories highlights its potential therapeutic value, more studies are still needed to understand this possible therapy’s effectiveness, mechanism of action, and ideal dosing; especially in certain patient populations, such as post-operative Mohs surgery patients.

In this study we attempted to characterize the efficacy, utility, and practicality of autologous PRP on the closure of wounds healing by second intent in patients who had recently undergone Mohs surgery for the removal of a non-melanoma skin cancer. After screening and selection of suitable patients for our study (Table 1), we administered autologous PRP to these select patients’ wounds and observed their healing trajectories over a 12-week period, assessing for wound regression, tissue regeneration, and ultimately the complete recovery of their wounds as measured by the standardized Bates-Jensen Wound Assessment Scale (Figure 2).¹⁰ Our goal was to characterize whether or not PRP is a viable treatment option in select post-operative Mohs surgery patients with wounds having to heal by second intent.

Figure 2. The Bates-Jensen Wound Assessment Scale contains 13 items that assess numerous wound parameters such as size, depth, edges, color, edema, etc. in an objective fashion (i.e. is the length x width of the wound <4 cm2, between 16.1 – 36 cm2, or >80 cm2). These metrics are then evaluated on a scale of 1 to 5 with a score of 1 indicating healthy attributes for each characteristic, while a score of 5 indicates unhealthy attributes for each scale metric. The scale ranges from 13 to 60 with a value of 13 indicating complete wound regeneration or “recovery,” and a value of 60 indicating complete wound degeneration. Each individual’s Bates-Jensen score was recorded, referred to for evaluation of progress, and updated throughout the course of the study to determine if wound healing was actually occurring.

Procedure

Mohs surgery patients were notified of our study and recruited either following their individual Mohs surgery (if their selected wound was appropriate for healing by second intent) or prior to their surgery during the clinical consult discussing the Mohs procedure (if their wound was likely to need to be closed by second intent, such as certain non-melanoma skin cancers located on the anterior leg). Patients were eligible for this study if they did not meet any of the exclusion criteria or contraindications to PRP use listed in Table 1. Patient inclusion into the study was considered on a case-by-case basis if they had any possible risk factors for PRP use (also listed in Table 1). All enrolled subjects’ medical records were reviewed before receiving a consent form for participation in this study as this was proper Mohs surgical protocol at the facility where this research was taking place.

After study subjects had undergone Mohs surgery for the treatment of their non-melanoma skin cancer, an 8-22mL sample of whole blood (depending on the size of the patient’s defect) was drawn from their antecubital fossa. This sample was then centrifuged to separate out the PRP from the rest of the patient’s whole blood. The newly isolated PRP was then injected in a sterile fashion back into the surgical wound site, as well as extending 5mm. in diameter from the wound. Prior to PRP administration, the surgical wound was measured and photographed, and an assessment of the surgical wound was done with the Bates-Jensen Wound Assessment Scale. PRP was re-administered to the wound site at two to four week intervals for up to 12 weeks for each patient; the interval was dependent upon how fast a patient’s wound was improving after assessment by the Bates-Jensen Scale. Patients were seen at weekly intervals to assess for wound healing via photographs and a weekly Bates-Jensen wound score. Administration of PRP at these varying intervals followed the same protocol as the first injection. If complete wound healing occurred prior to the 12-week interval, further PRP injections were not performed. For a full, detailed experimental procedure see Appendix 1.

Figure 3. Patient Images and Comments

Figure 4. The average time to recovery (“recovery” = 13 on the BJWAS, represented by the horizontal red line on Figure 4) for the 4/5 patients who actually achieved complete wound regeneration within the study’s allotted timeframe was 7 weeks. The enrolled patients in this study categorized as “recovered” included: Patient #2 in 5 weeks, Patient #3 in 4 weeks, Patient #4 in 11 weeks, and Patient #5 in 8 weeks. The only patient enrolled in this study to not make a full recovery within the 12 week timeframe was Patient #1 (Week 12 BJWAS score = 19). So, ultimately, 80% (4 out of 5) of patients that were enrolled in this case series successfully recovered prior to the 12 week allotted timeframe for this study.* *Twelve weeks was the greatest length of time patients’ insurance companies would compensate the facility this research was taking place at for surgical wound care post-op regardless of the type of surgical wound, size of the defect, and individual patient characteristics. This was often not enough time for a patient to achieve complete wound recovery, especially if their wound had to heal via second intent. One of our goals with PRP was to see if we could consistently beat this 12 week deadline in patients with surgical defects having to heal by second intent."

Discussion

Autologous PRP is a viable treatment option for post-op Mohs surgical wound healing by second intent depending on wound site, proper patient selection/enrollment, and individual environmental factors that may influence wound healing trajectories for each patient. During the course of this study, it was observed that patients who waited longer between PRP injections had definitive stalls in their wound scores. In the weeks following autologous PRP administration, patients seemed to show the greatest decrease in score and thus improvement in wound regeneration. Also, the one patient enrolled in the study that did not make a complete wound recovery prior to the 12-week deadline improperly followed wound care protocols and had extraneous variables impede his recovery (i.e. malnourishment), thus highlighting some limitations of PRP in certain patient populations and wound healing trajectories. His example further reinforces the importance of proper patient selection/enrollment and environmental factors in PRP treatment protocols.

These aforementioned sentiments indicate that barriers to the efficacy of PRP in wound healing trajectories, particularly in the final stages of wound healing, still exist. PRP helps significantly with tissue granulation early on, but not as much with tissue re-epithelialization later on in the wound healing cycle. One notable bright spot on the efficacy of PRP in wound healing trajectories is that immunosuppression was not as significant a barrier as was originally thought. If patients are properly selected for, PRP might be an effective alternative for quicker recovery post-Mohs in this vulnerable patient demographic; future research should capitalize on this novel finding. In fact, more research in general is still needed to clearly identify and delineate the most ideal healing trajectories for all stages of wounds healing by second intent in all different kinds of patient populations. Ideally, this would be done as large-scale studies, but the relatively niche wound healing scenarios PRP is effective for might make this difficult to accomplish. In the future, PRP should be utilized in conjunction with other treatment modalities to maximize tissue regeneration and minimize recovery times. Overall from this small study, PRP did show efficacy as a wound recovery modality with minimal complications when compared broadly to therapeutic alternatives for surgical wounds healing by second intent. The authors of this study would recommend it as a possible tertiary option to keep in mind for providers caring for patients meeting the appropriate inclusion/exclusion criteria without contraindications or risk factors that have second intent surgical wounds refractory to other treatment options.

The authors have no relevant disclosures.