Platelet, fibrin and leukocyte-rich clot (PFLRC) clot for diabetic foot ulcer healing - Cases report

Joan  Pedraza-La Barrera; Mareth Fiorella  Landeo-Solis; Dante Horacio Rodriguez-Alonso; Diego Armando  Rosas-Garay; Jorge  Rosas-Oliveros; Lizzie Karen  Becerra-Gutiérrez; Stalin Tello-Vera

doi:10.23750/abm.2026.18346

Platelet, fibrin and leukocyte-rich clot (PFLRC) clot for diabetic foot ulcer healing - Cases report

Authors

Joan Pedraza-La Barrera Department of Pathology – Bellavista Hospital II-E, Lima, Peru; Faculty of Medicine, Cayetano Heredia Peruvian University, Lima, Peru https://orcid.org/0000-0001-6698-3394
Mareth Fiorella Landeo-Solis Faculty of Medicine, Cayetano Heredia Peruvian University, Lima, Peru https://orcid.org/0009-0009-1232-3177
Dante Horacio Rodriguez-Alonso Faculty of Medicine, National University of Trujillo, Trujillo, Peru https://orcid.org/0000-0002-6662-9210
Diego Armando Rosas-Garay Faculty of Medicine, Continental University, Lima, Peru https://orcid.org/0009-0004-2865-5321
Jorge Rosas-Oliveros Clínica Perimedic, Lima, Peru https://orcid.org/0000-0001-8243-7932
Lizzie Karen Becerra-Gutiérrez Faculty of Human Medicine, San Martin de Porres University, Chiclayo-Peru; Research Laboratory, Research Department, Hospital Regional Lambayeque, Chiclayo, Peru https://orcid.org/0000-0001-8243-7932
Stalin Tello-Vera Molecular Biology Laboratory, Almanzor Aguinaga Asenjo National Hospital, Chiclayo-Peru; Faculty of Human Medicine, Pedro Ruiz Gallo National University, Chiclayo-Peru https://orcid.org/0000-0002-3687-8072

Keywords:

fibrin rich in platelets, foot ulcer, diabetic foot, therapy biological

Abstract

Diabetic foot ulcers (DFUs) are common and serious complications of diabetes, associated with a high risk of infection, amputation, and reduced quality of life. Conventional therapies, such as biocompatible dressings, have limited regenerative capacity and are costly, especially in developing countries. Orthobiological agents such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in gel form have shown potential for healing, but their preparation is complex. The study presents the efficacy of a new regenerative therapy protocol for diabetic foot using a low-cost, easily obtainable autologous three-dimensional orthobiological agent or clot rich in red blood cells, fibrin, platelets, and leukocytes (RF-LR). Three clinical cases of patients with DPF treated with four sessions of RF-LR are reported. Complete closure of the lesions was observed, with no recurrence for at least three months. Preliminary results suggest that RF-LR could be a safe, effective, and affordable alternative to conventional treatments and more complex orthobiological therapies. However, randomised controlled clinical trials are needed to validate its efficacy and establish its application in standardised therapeutic protocols.

References

1. Lukin P, Kuchumov AG, Zarivchatskiy MF, Kravtsova T. Clinical Classification of the Diabetic Foot Syndrome Adapted to ICD-10 as a Solution to the Problem of Diagnostics, Statistics and Standardisation. Medicina (Kaunas). 2021;57(8):817. doi: 10.3390/medicina57080817.

2. Martínez-Escalante JE, Romero-Ibargüengoitia ME, Plata-Álvarez H, et al. Diabetic foot in Mexico: risk factors for 5-year mortality after major amputation in a secondary public health hospital. Cir Cir. 2021;89(3):284-290. doi:10.24875/CIRU.20000209.

3. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta- analysis†. Ann Med. 2017;49(2):106-16. doi: 10.1080/07853890.2016.1231932.

4. Bandyk DF. The diabetic foot: Pathophysiology, evaluation, and treatment. Semin Vasc Surg. 2018;31(2-4):43-8. doi: 10.1053/j.semvascsurg .2019.02.001.

5. American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S20-S42. doi: 10.2337/dc24-S002. PMID: 38078589; PMCID: PMC10725812.

6. Matta-Gutiérrez G, García-Morales E, García-Álvarez Y, Álvaro- Afonso FJ, Molines -Barroso RJ, Lázaro-Martínez JL. The Influence of Multidrug-Resistant Bacteria on Clinical Outcomes of Diabetic Foot Ulcers: A Systematic Review. J Clin Med. 2021;10(9):1948. doi: 10.3390/jcm10091948.

7. Behroozian A, Beckman JA. Microvascular Disease Increases Amputation in Patients With Peripheral Artery Disease. Arterioscler Thromb Vasc Biol. 2020;40(3):534-40. doi: 10.1161/ATVBAHA.119.312859.

8. Fernández-Guarino M, Hernández-Bule ML, Bacci S. Cellular and Molecular Processes in Wound Healing. Biomedicines. 2023;11(9):2526. doi:10.3390/biomedicines11092526.

9. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol. 2020;10(9):200223. doi:10.1098/rsob.200223.

10. Ma H, Siu WS, Leung PC. The Potential of MSC- Based Cell-Free Therapy in Wound Healing —A Thorough Literature Review. Int J Mol Sci. 2023; 24(11):9356. doi: 10.3390/ijms24119356.

11. Aldana PC, Khachemoune A. Diabetic Foot Ulcers: Appraising Standard of Care and Reviewing New Trends in Management. Am J Clin Dermatol. 2020;21(2):255-64. doi: 10.1007/s40257-019-00495-x.

12. Pérez-Panero AJ, Ruiz-Muñoz M, Cuesta-Vargas AI, Gónzalez -Sánchez M. Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: A systematic review. Medicine (Baltimore). 2019;98(35):e16877. doi:10.1097/MD.0000000000016877.

13. Miron RJ, Gruber R, Farshidfar N, Sculean A, Zhang Y. Ten years of injectable platelet-rich fibrin. Periodontol 2000. 2024;94(1):92-113. doi: 10.1111/prd.12538.

14. Miron RJ, Pikos MA, Estrin NE, et al. Extended platelet-rich fibrin. Periodontol 2000. 2024;94(1):114-30. doi: 10.1111/prd.12537.

15. Wong AYW, Ong BSY, Lee ARYB, et al. Topical Biological Agents as Adjuncts to Improve Wound Healing in Chronic Diabetic Wounds: A Systematic Review of Clinical Evidence and Future Directions. Cureus. 2022;14(7):e27180. Published 2022 Jul 23. doi:10.7759/cureus.27180.Yessentayeva SY, Orakbay LZ, Adilhanova A, Yessimov N. Approaches to the use of stem cells in regenerative medicine. Anal Biochem. 2022;645:114608. doi: 10.1016/j.ab.2022.114608.

16. Wang Y, Wang X, Chen R, et al. The Role of Leukocyte-Platelet-Rich Fibrin in Promoting Wound Healing in Diabetics Foot Ulcers. Int J Low Extrem Wounds. 2024;23(2):306-14. doi: 10.1177/15347346211052811.

17. Chen J, Wan Y, Lin Y, Jiang H. Platelet-rich fibrin and concentrated growth factors as novel platelet concentrates for chronic hard-to-heal skin ulcers: a systematic review and meta- analysis of randomized controlled trials. J Dermatolog Treat. 2022;33(2):613-21. doi: 10.1080/09546634.2020.1773386.

18. Saboia-Dantas CJ, Dechichi P, Fech RL, de Carvalho Furst RV, Raimundo RD, Correa JA. Progressive Platelet Rich Fibrin tissue regeneration matrix: Description of a novel, low cost and effective method for the treatment of chronic diabetic ulcers-Pilot study. PLoS One. 2023;18(5):e0284701. doi: 10.1371/journal.pone.0284701.

19. Deng J, Yang M, Zhang X, Zhang H. Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcer healing: a systematic review and meta- analysis of randomized controlled trials. J Orthop Surg Res. 2023;18(1):370. doi:10.1186/s13018-023-03854-x.

20. Peng Y, Wang J, Liu X, et al. Efficacy of Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcers: A Systematic Review and Meta- Analysis. Ann Vasc Surg. 2024 Jan;98:365-73. doi: 10.1016/j.avsg .2023.05.045.

21. Hossam EM, Alserr AHK, Antonopoulos CN, Zaki A, Eldaly W. Autologous Platelet Rich Plasma Promotes the Healing of Non- Ischemic Diabetic Foot Ulcers. A Randomized Controlled Trial. Ann Vasc Surg. 2022 May;82:165-71. doi: 10.1016/j.avsg.2021.10.061.

22. Helal M, Elwakeel H, El Sorogy M, Abdelmaksoud M, Abdelgawad M. Effectiveness of autologous leukocyte and platelet-rich fibrin (L-PRF) in management of chronic diabetic foot ulcers.The Egyptian Journal of Surgery. 2024; 43(4): 1540-7. doi: 10.21608/EJSUR.2024.297983.1104.

23. Yang M, Deng B, Hao W, et al. Platelet concentrates in diabetics foot ulcers: A comparative review of PRP, PRF, and CGF with case insights. Regen Ther. 2025 Feb 21;28:625-32. doi: 10.1016/j.reth.2025.02.005.

24. Kim J, Nomkhondorj O, An CY, Choi YC, Cho J. Management of diabetic foot ulcers: a narrative review. J Yeungnam Med Sci. 2023 Oct ;40(4):335-42. doi: 10.12701/jyms.2023.00682.

25. Snyder RJ, Schultz G, Wachuku C, Rashid AM, Ead JK. Proposed Mechanism of Action of Topically Applied Autologous Blood Clot Tissue. J Am Podiatr Med Assoc. 2023;113(3):20-140. doi: 10.7547/20-140.

26. Olszewska A, Duan J, Javorovic J, et al. Manufacture and Initial Characterization of RAPIDTM Biodynamic Haematogel, an Autologous Platelet and Leukocyte-Rich Plasma Gel for Diabetic Foot Ulcers. Gels. 2024 Sep 2;10(9):572. doi: 10.3390/gels10090572.

27. Chiu A, Sharma D, Zhao F. Tissue Engineering-Based Strategies for Diabetic Foot Ulcer Management. Adv Wound Care (New Rochelle). 2023 Mar;12(3):145-67. doi: 10.1089/wound.2021.0081.

28. Kartika RW, Alwi I, Suyatna FD, et al. The role of VEGF, PDGF and IL-6 on diabetic foot ulcer after Platelet Rich Fibrin + hyaluronic therapy. Heliyon. 2021 Sep 7;7(9):e07934. doi: 10.1016/j.heliyon.2021.e07934.

29. Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018 Jan;1411(1):153-65. doi: 10.1111/nyas.13569.