Wound Healing in Stage IV Pressure Injury With Use of Adjunct Autologous Activated Platelet-rich Plasma Therapy: A Case Report

PI are lesions which are caused by prolonged pressure on a body part. Elderly, multimorbid, immobile, and paraplegic patients are at a higher risk of developing PI.¹ Patients with COVID-19 who also have ARDS are especially susceptible to PI as they remain immobile for extended durations while intubated.² aaPRP is an easily accessible biologic adjuvant which promotes wound healing through various bioactive factors.^3,4 This report presents a case of stage 4 PI in which intravenous and intralesional aaPRP was utilized as adjuvant therapy.

A 68-year-old male came to the outpatient clinic of Dr. Ramelan Navy Hospital, Surabaya, with a gaping wound in the sacral area. The patient also had a comorbidity of type 2 diabetes, which was controlled with oral antidiabetics. He was previously bedridden in the ICU for 2 months due to severe COVID-19 and started to develop an ulcer as a result, despite existing preventive protocols such as the use of a pressure-relieving mattress, bihourly patient repositioning, and application of skin moisturizer at high-risk areas twice daily. He then continued to develop lower extremity weakness, which rendered him to be only passively mobilized by wheelchair.

Upon presentation, the wound was debrided by a general surgeon (Figure 1), and a referral to plastic surgery was made. Topical cream consisting of 2 mg of hyaluronic acid per every 10 mg silver sulfadiazine and a framycetin sulphate tulle dressing were applied to the wound. Afterward, the patient and his family were informed of adjunct aaPRP therapy. Subsequently, informed consent was gained for aaPRP administration and inclusion to this report. This study was approved by the IRB.

The first dose of aaPRP was administered via intralesional injection and intravenous infusion (day 1). Subsequent aaPRP administration and evaluation were conducted approximately every 2 weeks: day 15 (Figure 2), day 30 (Figure 3), and day 44 (Figure 4). In between treatment visits, the patient’s family applied the aforementioned cream and gauze every 2 days.

The aaPRP used was prepared with a protocol that the authors of the present study developed. The authors used 24 mL of venous blood and divided it into 8 tubes containing sodium citrate and centrifuged at 1000 rpm for 10 minutes. The separated plasma was subjected to another round of centrifugation at 3000 rpm for 10 minutes. The pellets of platelet were then isolated by discarding the excess platelet-poor plasma until 2.5 mL of plasma remained. The final step of activation, which lyses all possibly remaining thrombocytes, renders the aaPRP safe for intravenous administration.⁵ This was achieved by the addition of 0.15 mL of calcium activator (H-Remedy, HayandraLab, Indonesia) to each of the tubes. After the consequent clots were removed, 10 mL of normal saline was added to each of the tubes.

PI remains a major burden worldwide, with an incidence of up to 3 million patients in the United States alone.⁶ The treatment of PI is also costly and may be a financial burden to patients. In the United States, treatment of a hospital-acquired stage 4 PI and its related complications can cost over $120 000 during one admission. This may also be due in part to the increased length of stay. Conditions prevalent among patients with PI include pain, depression, infection, osteomyelitis, and sepsis.⁷

In this case, the patient was admitted to the ICU during a nationwide surge of COVID-19 cases. While ICU patient protocols do exist, they are difficult to uphold when staff in the ICU are severely shorthanded. Staff shortages may have hindered the ability to moisturize and reposition the patient properly.⁸ Various types of pressure-relieving mattresses exist in the market that aim to optimize the distribution of body pressure. However, a 2021 systematic review stated that current evidence is still insufficient to determine the best type of mattress in preventing PI incidence. Nevertheless, the study concluded that alternating pressure (active) air surfaces are more cost-effective than reactive (static) foam surfaces in terms of preventing new PI.⁹

The cytokine storm may be a key player in PI pathogenesis in patients with COVID-19. Heavy systemic inflammation and cardiopulmonary dysfunction may cause local microthrombi in patients. At the same time, proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha from the storm also exacerbate the inflammation and ischemia in the PI-afflicted region.¹⁰ Therefore, simultaneous control of systemic and local inflammation in PI is essential in the management of PI in patients with COVID-19.

The presence of diabetes may also lower wound healing rates due to growth factor deficiency.¹¹ In the TIMERS model of wound healing, deficiency of growth factors may impede wound edge advancement.¹² Intravenous and intralesional aaPRP achieves systemic and local inflammation control through various proteins such as interleukin-1 receptor antagonist, vascular endothelial growth factor, platelet-derived growth factor, and epidermal growth factor.^3,4 As such, aaPRP administration also provides much-needed growth factors to the lesion.

Although other groups have previously treated PI with intralesional/intradermal platelet-rich plasma, the current authors believe their group is the first to also administer it intravenously. They have also previously utilized intravenous aaPRP to curb inflammation in patients with severe COVID-19 infection.¹³

Throughout the healing process, no infection was observed in the patient. Besides the application of framycetin, adjunct administration of aaPRP may also play a role in preventing infection, as it has been shown to exhibit synergism with antibiotics.¹⁴

The sole subject reported in this study design translates to a clear weakness. Furthermore, no analysis was conducted in determining the association between the aaPRP dose nor the frequency of administration with the observed outcome. The optimal dose of aaPRP is also yet to be determined.

While reports of improved PI healing with platelet-rich plasma are abundant, the current case adds evidence to the existing literature and demonstrates the potential that adjunct systemic and local administration aaPRP has in delivering a highly satisfactory result of PI healing. As prevention is always better than cure, the authors also encourage health care practitioners to take preventive measures with regards to PI. The adjunct administration of aaPRP would not have been optimal without diligent repositioning and meticulous care from the patient’s family. The administration of intravenous and intralesional aaPRP in PI patients should be further researched in well-designed clinical trials.