Autologous Platelet-rich Plasma for the Treatment of Nonhealing Perineal Wounds: A Report of Two Cases

Patients with perineal wounds often encounter difficulty in local wound healing. Historical research has identified a number of factors that have been associated with delayed or nonhealing perineal wounds postoperatively. Sex, age, perioperative steroids, wound management, degree of contamination at operation, and the presence of postoperative inflammation or improper care are associated with a nonhealing perineum following surgery.¹ These patients may require frequent trips to outpatient clinics or need in-hospital irrigation performed by medical or paramedical personnel; in addition, they often require intensive wound care for several months. Impaired perineal wound healing can prolong a patient’s hospitalization time and result in severe physical and mental impairment, and there is a risk of developing a persistent sinus infection after 1 year.²

The healing of soft tissues is mediated by a complex array of intracellular and extracellular events. Platelets are necessary and fundamental components of the process of wound healing.³ Platelets contain a variety of growth factors, coagulation factors, cytokines, adhesion molecules, chemokines, and integrins. When platelets are activated, these elements are released, which increases their concentrations to levels significantly above baseline blood levels.⁴ PRP is, by definition, derived from autologous blood using a centrifugation system that has above-baseline platelet and growth factor levels. PRP gels can facilitate growth factor release from the α-granules found in platelets. These growth factors facilitate anti-inflammatory, anabolic, and analgesic effects.^5-7 Previous studies have shown numerous benefits of the use of PRP for a diverse range of clinical applications in areas such as maxillofacial surgery, chest surgery, cardiovascular surgery, plastic surgery, androgenetic alopecia treatment, traumatology, and nephrology.^8,9 PRP gels are increasingly being used to manage wound healing.^10-12 With the objective of decreasing patient suffering from nonhealing wounds, PRP products have been used to improve perineal wound healing.

The following case report details 2 patients with perineal wounds that failed to heal for more than 2 months after hemorrhoidectomies and were subsequently healed with autologous PRP treatment. The discussion also includes the outcomes and feasibility of PRP treatment in patients with nonhealing perineal wounds.

Case 1

A 21-year-old male had undergone surgery for hemorrhoids and Fournier’s gangrene of the perineum 2 months prior. Routine dressing changes were performed after surgery. However, the wound size was unchanged from approximately 8.0 cm in longest diameter (Figure 1A). The patient reported pain and explained that the wound affected his quality of life. The clinician evaluated the patient’s condition and recommended autologous PRP treatment.

The patient’s blood (150 mL) was collected via intravenous puncture into the first bag in a trigeminy blood bag with CPDA-1 blood preservation solution (Nigale, Sichuan, China). The blood sample was centrifuged for 10 minutes at room temperature at 1500 rpm. The upper layer of plasma rich in platelets was pressed gently into the middle bag without any anticoagulant, where it separated from the lower layer of red blood cells. The plasma was then centrifuged for 15 minutes at 3000 rpm, and the platelets were collected in the bottom of the bag. The upper layer of platelet-poor plasma was pressed gently into the third bag without any anticoagulant, and the platelet pellet was combined with platelet-poor plasma to produce 20 mL of PRP. The end product was made into 2 doses of 10 mL for 2 treatments. The platelet count of the final product was 1480 × 10⁹/L, with an approximately 4-fold increase in platelet concentration over whole blood. Two milliliters of the PRP product were injected subcutaneously into each of 8 points around the wound without platelet activator. The platelet activator (5000 U of thrombin lyophilized powder dissolved in 8 mL of 3% w/v calcium chloride solution) was added to the remaining PRP at a ratio of 1:10 to produce PRP gel, which was applied to the wound surface and covered with oil gauze to keep the wound moist. The outermost layer was covered with sterile gauze. The PRP gel and gauze dressings were changed once every 5 to 7 days.

At a follow-up visit 5 days after the first PRP treatment, the patient had recovered well. The wound surface had distinctly decreased in size (to < 4.0 cm) and exhibited signs of healing (Figure 1B). The patient reported that the pain was reduced on the second day after treatment and was completely gone after 5 days, and that his movement was normal. After being evaluated, the patient underwent a second treatment with externally applied PRP gel. He returned 8 days later, by which time the wound had fully closed without any side effects (Figure 1C).

Case 2

A 37-year-old male reported a chief concern of recurrent anal pruritus with damp discomfort for more than 6 months accompanied by pain during defecation. He was diagnosed with hemorrhoids and perianal eczema. The patient underwent Milligan-Morgan hemorrhoidectomy. However, approximately 1.5 cm in longest diameter of the wound failed to heal after more than 2 months (Figure 2A). The autologous PRP gel was prepared using the same procedures as for case 1. The patient was externally treated with autologous PRP gel. A routine blood test showed that the platelet count of the final PRP product was 717 × 10⁹/L, 3 times the whole blood platelet count. The PRP product was applied externally to the patient’s wound as described above. At a follow-up visit a week later, the patient’s wound had reduced to 0.8 cm in diameter (Figure 2B). The patient then underwent a second treatment with externally applied PRP gel. At the second follow-up visit after another 7 days, the patient was recovering well with full wound closure (Figure 2C).

For patients with wounds that are easy to reach, the conventional care methods of debridement, drainage, and timely wound dressing changes are adequate. However, other wounds, particularly those in areas that are difficult to care for, can remain refractory to healing. The healing process for perineal wounds can be delayed due to difficulty in administering proper care. Poor blood microcirculation and decreased levels of local growth factors in perineal wounds make healing even more difficult. Therefore, it is very important to find more effective treatments, and the cases described above suggest that PRP gels may provide an ideal solution.

PRP is a platelet concentrate extracted from autologous blood by centrifugation. After activation, platelets can release a large number of growth factors, such as platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, fibroblast growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor.^4,13 These growth factors have been proven to promote soft tissue and skin healing, and there is good synergy among growth factors. In addition, PRP has no side effects on patients owing to it being derived from autologous blood.

The 2 cases both featured patients with perineal wounds that were problematic for more than 2 months and, in both cases, were associated with persistent pain. The best practice for such cases is to maximize the chances of primary wound healing.¹⁴ For both patients, a week of PRP treatment relieved the pain associated with the nonhealing wounds and promoted the healing process. Despite the existence of several reports on the use of PRP for perianal fistulas,^11,15 there have been no reports on the use of PRP in the treatment of nonhealing perineal wounds after hemorrhoidectomies. In case 1, the concentration of platelets in the PRP product was a 4-fold increase from that in whole blood, whereas in case 2 it was 3 times the level in whole blood. Nevertheless, the result of PRP treatment in case 2 is exciting. The difference in the final platelet concentration is related to the patient’s basic platelet count and the operator’s subjective assessment during the preparation process. A final platelet concentration of 3 to 5 times the initial concentration appears to be a reasonable and effective range. In case 1, the patient’s nonhealing wound was large, deep, and approximately 8.0 cm in diameter, so it was necessary to administer a subcutaneous injection to enhance deep tissue repair. In case 2, the nonhealing wound was small, shallow, and approximately 1.5 cm in diameter, so subcutaneous injection was necessary and only external application was used to promote wound healing.

Although this report describes results from the treatment of only 2 patients, the observations are promising. These cases demonstrate that autologous PRP is feasible and economical to produce as well as safe for use in patients with nonhealing perineal wounds.

During the preparation of PRP, the content was not exposed to the environment, there was no risk of contamination of the final PRP product, and no side effects occurred in either of the 2 patients. Compared to other commercial devices on the market¹⁶ the trigeminy blood bag used in the current cases to produce PRP has the double advantage of being both inexpensive and having a large capacity.

This report describes the effectiveness of PRP in perineal wound healing, however it is limited by the small number of cases. Also, there were no controls to compare the efficacy of PRP to other modalities. In addition, data on quality control for PRP were not available, making it difficult to determine the influence of the concentration of platelets on PRP effectiveness. Thus, there is a strong need for further studies on a larger number of patients using standardized guidelines for PRP production and objective treatment outcome measures to conclusively evaluate the impact of PRP on the management of nonhealing perineal wounds.

After perineal surgery, PRP treatment may be a viable, efficacious, and safe means to promote wound healing and shorten rehabilitation time. Further investigation is needed, preferably via a randomized study, to assess the usefulness of PRP gels as treatments to improve the efficiency and efficacy of perineal wound healing.