Homologous Platelet Gel for the Management of Refractory Diabetic Lower Extremity Ulcers

Sara Ferreira, MD shares key details from her original research paper, “Use of Homologous Platelet Gel to Manage Refractory Diabetic Lower Extremity Ulcers: Additional Experience at a Tertiary Hospital”; coauthors include Marco Sampaio, MD; Margarida Oliveira, MD; Francisco Dias, MSc; Eduarda Valente, MSc; Maria Luís Queirós, MSc; Rosa Guimarães, Lic; Joel Pereira, MSc; Helena Neto, MD; Rui Carvalho, MD; and Marika Bini Antunes, MD. Read the full paper here.

Transcript:

Hello, my name is Sara Ferreira. I am an immunotherapy doctor in the Department of Immunotherapy at Centro Hospitalar Universitario in Porto, Portugal.

This study was a collaboration between my department and the diabetic foot multidisciplinary unit. Lower extremity complications are common in patients with diabetes and are a major cause of morbidity, hospitalization, and lower limb amputation. Therefore, prompt and appropriate management of diabetic lower extremity ulcers is important, and new methods to achieve ulcer healing have been described including application of platelet-rich plasma or platelet gel. Wound healing is a complex process that involves multiple cells, extracellular matrices, and mediators such as growth factors and cytokines. Neuropathy, peripheral arterial disease, foot deformities and trauma contribute to development of foot ulcers in patients with diabetes. These patients also experience impaired wound healing, which can result in chronic wounds.

Platelet-rich plasma and platelet gel are rich in platelets and release growth factors, cytokines and chemokines that promote tissue regeneration, modulate the inflammatory response, and have an antibacterial effect owing to the chemotaxis of neutrophils, fibroblasts, macrophages, and smooth muscle cells to the wound site.

The use of platelet gel in diabetic wounds has been recommended by the Italian Society of Transfusion Medicine and Immunohematology since 2012, and use of this modality has increased since. In 2018, an observational study of patients with diabetic foot ulcers treated with platelet gel over 45 months at our center was published. The current study builds on that previous study with the observation period length and the number of patients increased to evaluate not only platelet gel effectiveness and safety but also the possible correlation between response to treatment and patient comorbidities. Data from patients with chronic refractory diabetic lower extremity ulcers managed with homologous platelet gel between January 2014 and October 2022 were evaluated: their comorbidities, wound characteristics, number and time of treatments, and the outcome. The outcome was classified as complete response when complete ulcer healing with revitalization was achieved, as partial response when at least AF of the area either reduction or there was an improvement in pain with the patient, or an absence of response.

A total of 81 patients with refractory ulcer standard treatments were proposed for platelet gel application. A total of 62 patients had 3 or more comorbidities. The outcome was evaluated in 69 patients with response observed in 49 of them: complete response in 32 and partial response in 17. Surprisingly, the only statistically significant relationship observed between response and the different comorbidities was between the presence of polyneuropathy and response, with worse outcomes in patients with polyneuropathy. Homologous platelet gel appears to be a safe and possibly effective therapeutic alternative, especially in these complex patients with chronic refractory diabetic ulcers that were unresponsive to standard therapies.

Yes, like I said, the use of homologous platelet gel was recommended by the Italian Medicine Transfusion Society since 2012, and since 2014 we started doing these treatments in our center because we had a few patients with chronic diabetic ulcers that were refractory to multiple standard treatments. So the unit, the diabetic foot multidisciplinary unit, in collaboration with us, we decided to start doing this type of treatment to see if we could help those patients. Like I said previously, most of these patients were very complex with a lot of comorbidities, with use of multiple drugs that could impair the platelets’ function, and therefore we use homologous platelet gel obtained from our blood donors and not autologous gel obtained from the patients themselves. And we observed that at least half of these patients were able to significantly improve their ulcers, some of them with complete responses and a lot of them with the partial responses. And that's why we wanted to publish these results, because in this kind of population that have ulcers for a lot of time, they don't respond to anything. This can be another therapeutic alternative for patients to try and try to resolve their situation.

Yes, I think the result that surprised me most was the fact that we didn't appear to observe a correlation between the presence of peripheral obstructive arterial disease and worse outcomes in patients. However, the number of patients in the subgroups were too small to achieve statistical power, so we also intend to continue to monitor the situation and increase the number of patients and reevaluate the situation and see if the peripheral arterial disease really doesn't affect the use of homologous platelet gel.

Like I said, we will continue to monitor our patients to collect data from everything, try to predict which comorbidities affect the outcome, and try to select better the patients that really benefit from this therapy,

No, just that really homologous platelet gel appears to be really good for these patients because even if only half of them were able to have a response, that's half of the patients that wouldn't be able to resolve their situation without this treatment, because they have tried almost everything that was available in Portugal, at least in our country, and nothing was resolving their situation. And even though the response rate, it's not 100%, like I said, they are very complex patients, and we were able to help those patients and achieve ulcer resolution. And I think everyone who has complex patients and who has a transfusion medicine service that can adapt and that have blood donors and that can produce the platelet gel, because it's not that difficult to do it, they should try to think of this as a really alternative therapy to try and try to help those patients.