Platelet-Rich Plasma in Non-Healing Diabetic Foot Ulcer : A Case Report

Dr. Kinnor Das

MBBS, MD (Dermatology, Venereology and Leprosy)

Consultant Dermatologist, Apollo Clinic Silchar

Assam, India

Introduction

Diabetic foot ulcer (DFU) is one of the most costly and devastating complications of diabetes mellitus, affecting around 15% of diabetic patients during their lifetime. It is the most prevalent and harmful diabetes side effect and is responsible for a significant percentage of diabetes-related hospitalizations. A diabetic foot ulcer can lead to severe complications, including preventable amputations and even mortality, particularly if they become infected or fail to heal properly. Effective management of diabetic foot ulcers is crucial, and early intervention can significantly reduce the severity of these complications.1, 2

A non-healing diabetic foot ulcer can be a major source of morbidity and disability for affected individuals. A nonhealing diabetic foot ulcer is a type of wound that is characterized by a breakdown of the skin and underlying tissue on the foot.2 A diabetic ulcer often develops in three stages called a callus

(which forms as a result of neuropathy), deformity of the foot and sensory loss that causes trauma. Finally, the trauma caused by the callus induces subcutaneous bleeding until it erodes and becomes an ulcer.3 People with diabetes are at a higher risk of developing foot ulcers due to a combination of factors, such as peripheral neuropathy (loss of sensation in the feet), peripheral vascular disease (poor blood flow to the feet), poorly controlled blood sugar levels and sometimes due to neuropathy (nerve damage). These factors make it difficult for the ulcers to heal and can also increase the risk of amputation.2

There are several risk factors associated with foot ulcers in patients with diabetes, including previous lower extremity amputation, history of a foot ulcer, anatomic foot deformity, peripheral vascular disease, diabetic nephropathy in those on dialysis, poor glycemic control, and smoking. These risk factors can increase the likelihood of developing foot ulcers in patients with diabetes. Patients with one or more of these risk factors should be monitored closely for the development of foot ulcers, and appropriate preventive measures should be taken to minimize the risk of ulceration. Regular foot exams, patient education about proper foot care, and appropriate medical management of underlying conditions such as poor glycemic control and peripheral vascular disease are all important components of preventing foot ulcers in patients with diabetes.4 Both retrospective and prospective investigations have demonstrated that increased plantar pressure causes many plantar ulcers to form in diabetic patients and that ulceration frequently precedes lower extremity amputation.5

Case report

A 72-year-old, male patient presented to our outpatient department with non-healing ulceration over the right heel and calf for five months. He had a medical history of uncontrolled type 2 diabetes mellitus and was on oral hypoglycaemic medicines and subcutaneous insulin for 24 years. On examination the edges of ulcers were firm, and the floor of ulcer was covered with purulent discharge. The temperature of surrounding skin was bit elevated and the surrounding skin was taught. There was no tenderness though. Regional lymph nodes were palpable and tender. The dorsalis pedis artery pulsation of right feet was feeble. Some basic laboratory and radiographic investigations were conducted. The serum creatinine was slightly raised. X-ray didn’t reveal any bony abnormality. On the initial day patient was given basic wound care by changing daily dressing and wound debridement along with some general antibiotics. The conservative treatment did not show a satisfactory result. Platelet-rich plasma (PRP) therapy was suggested looking at the condition. Few other therapies like wound care, systemic medication along with PRP treatment was given as well. The patient was kept on regular follow up to check the reduction in wound size and to avoid any adversity of the wound. PRP was injected at the base and the margins of the ulcer at an interval of two weeks. All diabetic foot ulcers responded positively with no adverse reaction. The ulcers were healed within 3 months of treatment. No ulceration or swelling was found with complete skin epithelialisation.

Before treatment

After 3 months of treatment

Figure 1: Ulcerated surface along with swollen border and mild tenderness on the inner skin of the right calf

Before treatment

After 3 months of treatment

Figure 2: Non–healing ulceration, on the right heel

Diagnosis of diabetic ulcer

Although the diagnosis of a diabetic foot ulcer is straight forward, a thorough evaluation of the patient's medical history and a physical examination of the feet should be done.6 The history should cover the onset and duration of the condition, glycaemic control, other preexisting problems of diabetes, such as sensory neuropathy, history of peripheral vascular disease, callus formation, past ulcers, prior treatments, and the results. The location of the ulcer, any anatomical anomalies, symptoms of vascular insufficiency, and the peripheral pulses of the foot are all examined during the clinical examination.3

With Semmes-Weinstein monofilament, diabetic peripheral neuropathy can be evaluated. For the diagnosis of peripheral neuropathy and unusual presentations, nerve and skin biopsy are additional means of examination. Plain X-rays are used to assess osteomyelitis or any other bone involvement. The probeto-bone - test can be done that involves using a sterile metal probe to probe the ulcer. The probability of osteomyelitis is minimal after a negative test in an outpatient or lowrisk scenario. After a positive test in a high-risk or inpatient environment, the chance of osteomyelitis is high. 3, 6

Treatment

The primary goal of treatment for non-healing diabetic foot ulcers is to promote healing and prevent infection, which may include off-loading or redistributing weight from the affected area, wound care and debridement, antibiotics to treat or prevent infection, treatment of underlying conditions such as diabetes or peripheral vascular disease and regular follow-up with a wound care specialist or foot care specialist.2 The management of diabetic foot ulcers typically requires a multidisciplinary team approach, as a holistic approach to wound management is necessary to address the various factors that contribute to the development and progression of diabetic foot ulcers. Blood sugar control, wound debridement, advanced dressings, and offloading modalities are generally considered key components of diabetic foot ulcer management. In some cases, surgery may also be necessary to promote healing and prevent the recurrence of chronic ulcers. Additionally, adjunct therapies such as hyperbaric oxygen therapy, electrical stimulation, negative pressure wound therapy, bioengineered skin, and growth factors may be used to expedite the healing process.1

It appears that people with diabetes must practise the right self-care behaviours in order to prevent diabetic foot ulcers, including wearing offloading footwear, exercising, eating a healthy diet, checking their blood sugar levels, taking medicine, and taking care of their feet.7

Patient education and regular foot care are also essential in preventing diabetic foot ulcers and their complications. Patients should be educated about proper foot care, including daily inspections, proper footwear and foot hygiene. They should also be advised to seek prompt medical attention for any signs of foot injury or infection. Overall, a comprehensive and individualized approach to diabetic foot ulcer management is necessary to achieve optimal outcomes.1 Wound care typically involves cleaning the wound and removing any dead tissue, as well as controlling any infection that may be present. Topical or oral antibiotics may be prescribed, and a dressing may be applied to the wound to help promote healing.2, 3 Off-loading of the affected limb is also important in the management of nonhealing diabetic foot ulcers. This may involve the use of special shoes, inserts, or bracing to redistribute weight and pressure away from the ulcer.2 Additionally, blood sugar levels should be well controlled before and during the treatment.3

Treatment of a non-healing diabetic foot ulcer with platelet-rich plasma (PRP) is a minimally invasive option that utilizes a patient's own blood platelets to promote healing and tissue regeneration. The growth factors in the PRP help to reduce inflammation, promote blood flow, and stimulate the growth of new cells and tissue, which can aid in the healing process and reduce the risk of amputation in patients with diabetic foot ulcers. These growth factors have a crucial role in regulating the recruitment, proliferation, and production of extracellular matrix by mesenchymal cells during the healing process. A polypeptide called plateletderived angiogenesis factor is known to promote endothelial cell migration, which in turn promotes the formation of new capillaries.8 PRP has been shown to be effective in promoting healing in nonhealing diabetic foot ulcers. It can be used in conjunction with other treatments such as off-loading, wound care and antibiotics to treat or prevent infection.8 It has been found to improve wound healing rate and reduce wound size, compared to standard wound care alone.9 Platelets are rich in growth and healing factors an injured individual can get back to a pain-free life in four to six weeks. The use of PRP could help a patient avoid joint replacement surgery, and potentially back surgery. The main advantages of PRP is use of autologous blood, which eliminates the risk of allergic reactions or rejection and low cost and limited resource requirement in its preparation and lack of manpower resources.9, 10

Activated platelet-rich plasma (aPRP) is a treatment option that has been studied for its potential role in the treatment of diabetic foot ulcers. The treatment process is similar to traditional PRP, but it involves activating the platelets before they are applied to the wound.

Activation can be done using various methods such as thrombin or calcium chloride.9

Activation of platelets leads to the release of more growth factors and enzymes, which can enhance the healing process of the wound. aPRP has been shown to improve wound healing rate and reduce wound size in some studies.9, 10 The treatment may be repeated multiple times, depending on the severity of the ulcer and the patient's response to treatment.9

It is important to consult with a healthcare professional who is trained and experienced in the use of PRP to determine if this treatment is right for the patient and to ensure safe and appropriate administration.

Figure 3 ulcer; HB PAD, per Discussio

Discussion

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Figure 3 : Algorithm for prevention and care of the diabetic foot. ABI, Ankle-brachial index; DFU, diabetic foot ulcer; HBO, hyperbaric oxygen; MRI, magnetic resonance imaging; NPWT, negative pressure wound therapy; PAD, peripheral arterial disease; PTB, probe to bone; TcPO2, transcutaneous oxygen pressure; XR, radiography.2

A foot ul of these amputatio could sto the most recomme with diab infection improve The caus discovere linked to condition taken off of the sm lead and etic foot ulc gher local fo plantar press seriously dam aling proces essels in the ventually, ers are num ot pressures sure. Claw-t age the str s may be ha e legs and fe merous. 3 On s. There are oe deformit ructure of th mpered.5 An et, which is develop.3 betic foot. A ance imagin PO2, transcu iabetes-relate emand an interventio tic foot care National Ins foot ulcers, ted diabetic nly reduce t ne of the p e numerous ties and Cha he foot. Acco nother reaso s also seen i

BI, Ankle-b g; NPWT, n utaneous ox d lower ext amputation. n based on recommend titute for He including re foot ulcers, the risk of a precursors in structural is arcot neuroa ording to re on for diabeti n diabetes p

A foot ulcer is a predisposing factor in about 80% of diabetesrelated lower extremity amputations. At least 25% of these ulcers won't get well, and up to 28% could demand an amputation.2 This process from foot ulcer to amputation raises a variety of possible points where an intervention based on evidencebased recommendations could stop a major amputation. Thus, developing diabetic foot care recommendations is essential to guaranteeing the most economical use of healthcare resources.2 The National Institute for Health and Care Excellence (NICE) recommends a range of strategies rachial inde negative pre ygen pressu remity amp 2 This proce evidence-ba ations is es ealth and Ca egular foot a , and approp mputations the forma sues with th arthropathy esearch, if th ic foot infec patients. Vas x; DFU, di ssure woun re; XR, radi utations. At ss from fo ased recomm sential to gu are Excellen ssessments f riate woun and mortali tion of foo he foot that are the mos he ulcerated tions is athe cular compr ography. ot m d s r for managing diabetic foot ulcers, including regular foot assessments for patients with diabetes, early recognition and referral of suspected diabetic foot ulcers, and appropriate wound care and infection management. Effective management can not only reduce the risk of amputations and mortality but also improve the overall quality of life for diabetic patients.1

The causes of diabetic foot ulcers are numerous.3 One of the precursors in the formation of foot ulcers is discovered to be higher local foot pressures. There are numerous structural issues with the foot that have been linked to elevated plantar pressure. Claw-toe deformities and Charcot neuroarthropathy are the most frequent conditions that can seriously damage the structure of the foot. According to research, if the ulcerated foot is not taken offload, the healing process may be hampered.5 Another reason for diabetic foot infections is atherosclerosis of the small blood vessels in the legs and feet, which is also seen in diabetes patients. Vascular compromise can lead to necrosis and eventually, gangrene can develop.3

PRP is a non-operative; permanent solution utilizing the body’s natural healing process. In the case of nonhealing diabetic foot ulcers, PRP can be injected below and around the ulcers at a definite interval.8 These concentrated platelets contain platelet-derived growth factors, fibroblast growth factor, vascular endothelial growth factor, epidermal growth factor and transforming growth factor and other cytokines that promote healing and tissue regeneration.8,9

Several studies found that the use of PRP in the treatment of diabetic foot ulcers was associated with a significant reduction in wound size and an increase in wound healing rate. Factors such as the severity of the ulcer, the patient's overall health, and the presence of underlying conditions may affect the outcome of treatment.9

Conclusion

A non-healing diabetic foot ulcer is a very complicated condition seen in uncontrolled diabetic patients. A multidisciplinary approach to therapy is necessary to ensure the successful and rapid healing of diabetic foot ulcers. Wound debridement and the use of advanced dressings are necessary to facilitate healing and prevent infection. Surgery or some advanced therapies may be necessary in some cases to promote healing and prevent the recurrence of chronic ulcers. Overall, a rational and multidisciplinary approach to therapy is necessary to reduce the high morbidity and risk of serious complications resulting from diabetic foot ulcers. By utilizing these management strategies whenever feasible, the risk of amputation and other serious complications can be reduced, and patients can achieve optimal outcomes. PRP has been studied as a treatment option for diabetic foot ulcers and has shown promising results. PRP is believed to work by promoting the formation of new blood vessels and the growth of new tissue, which can help to speed up the healing process. It is also thought to have antiinflammatory and antioxidant properties that can help to reduce inflammation and prevent further damage to the wound. It is crucial to note that PRP should be used as adjunctive therapy, and not as a replacement for standard wound care and management of underlying diabetes.

Reference

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2. Hingorani, Anil; LaMuraglia, Glenn M.; Henke, Peter; Meissner, Mark H.; Loretz, Lorraine; Zinszer, Kathya M.; Driver, Vickie R.; Frykberg, Robert; Carman, Teresa L.; Marston, William; Mills, Joseph L.; Murad, Mohammad Hassan (2016). The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. Journal of Vascular Surgery, 63(2), 3S–21S. doi:10.1016/j. jvs.2015.10.003.

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7. Joseph Ngmenesegre Suglo, Kirsty Winkley, Jackie Sturt, "Prevention and Management of Diabetes-Related Foot Ulcers through Informal Caregiver Involvement: A Systematic Review", Journal of Diabetes Research, vol. 2022, Article ID 9007813, 12 pages, 2022. https://doi. org/10.1155/2022/9007813

8. Goda, Asser A. MDa,; Metwally, Mohamedb; Ewada, Ashrafb; Ewees, Hossama. Platelet-rich plasma for the treatment of diabetic foot ulcer: a randomized, doubleblind study. The Egyptian Journal of Surgery 37(2):p 178-184, Apr–Jun 2018. | DOI: 10.4103/ejs. ejs_139_17

9. Del Pino-Sedeño T, TrujilloMartín MM, Andia I, AragónSánchez J, Herrera-Ramos E, Iruzubieta Barragán FJ, SerranoAguilar P. Platelet-rich plasma for the treatment of diabetic foot ulcers: A meta-analysis. Wound Repair Regen. 2019 Mar;27(2):170182. doi: 10.1111/wrr.12690. Epub 2018 Dec 21. PMID: 30575212.

10. Steed DL, Goslen JB, Holloway GA, Malone JM, Bunt TJ, Webster MW. Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo. Diabetes Care. 1992 Nov;15(11):1598-604. doi: 10.2337/diacare.15.11.1598. PMID: 1468291.