Use of platelet rich plasma in the treatment of diabetic foot ulcers. Report of the experience
Abstract
Diabetic foot ulcers imply high expenditure for both patients and the health system. Vascular impairment, growth factor inhibition and cell migration, among other
factors, affect the chronicity of the condition. Platelet-derived growth factors (PDGFs) stimulate chemotaxis, neovascularization and tissue regeneration.
Objective: to evaluate effectiveness of a formulation of autologous platelet-rich plasma to complement the treatment of diabetic foot ulcer, assessing safety and
adverse effects.
Material: observational study. Platelet rich plasma was applied to six patients with chronic diabetic foot ulcer Wagner II, III, with an average delayed healing of 94
weeks. PRP gel was administered by puncture technique on the lesion, once a week until the ulcer healed or for 12 weeks. Diabetic foot ulcers were analysed in regards to
surface area and progression through the MobileWound Analyzer (MOWA) software to analyse ulcer images. The area reduction percentage was calculated comparing the initial measurement and that of week 12. The improvement criteria was defined in a reduction that is >70% of the lesion.
Results: men prevailed with an average age of 53 years ± 7.3. After 12 weeks of treatment an average reduction of 78% of the size of the ulcer was reported,
two complete healings and two 99% healed. One patient required amputation because of uncontrolled infection.
Conclusion: the application of PRP improved tissue regeneration and shortened the duration of the ulcer, promoting healing with no adverse effects, and it likewise eliminated the need for procedures to handle chronic ulcers.
References
2) Tzeng YS, Deng SC, Wang CH, Tsai JC, Chen TM, Burnouf T. Treatment of nonhealing diabetic lower extremity ulcers with skin graft and autologous platelet gel: a case series. Biomed Res Int 2013; 2013:837620.
3) Guest JF, Fuller GW, Vowden P. Diabetic foot ulcer management in clinical practice in the UK: costs and outcomes. Int Wound J 2018; 15(1):43-52.
4) Lavery LA, Davis KE, Berriman SJ, Braun L, Nichols A, Kim PJ, et al. WHS guidelines update: diabetic foot ulcer treatment guidelines. Wound Repair Regen 2016; 24:112-26.
5) Wu SC, Driver VR, Wrobel JS, Armstrong DG. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag 2007; 3(1):65-76.
6) Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, et al. Knee osteoarthritis injection choices: Platelet-rich plasma (PRP) versus hyaluronic acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskeletal Disord 2015; 8:1-8. doi: 10.4137/ CMAMD.S17894.
7) Knighton DR, Doucette M, Fiegel VD, Ciresi K, Butler E, Austin L. The use of platelet derived wound healing formula in human clinical trials. Prog Clin Biol Res 1988; 266:319-29.
8) Knighton DR, Ciresi K, Fiegel VD, Schumerth S, Butler E, Cerra F. Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet]derived wound healing formula. Surg Gynecol Obstet 1990; 170(1):56-60.
9) Paknejad M, Shayesteh YS, Yaghobee S, Shariat S, Dehghan M, Motahari P. Evaluation of the effect of plasma rich in growth factors (PRGF) on bone regeneration. J Dent (Tehran) 2012; 9(1):59-67.
10) Driver VR, Hanft J, Fylling CP, Beriou JM; Autologel Diabetic Foot Ulcer Study Group. A prospective, randomized, controlled trial of autologous platelet]rich plasma gel for the treatment of diabetic foot ulcers. Ostomy Wound Manage 2006; 52(6):68-74.
11) Anitua E, Aguirre JJ, Algorta J, Ayerdi E, Cabezas AI, Orive G, Andia I. Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers. J Biomed Mater Res B Appl Biomater 2008; 84(2):415-21.
12) Li L, Wang C, Wang Y, He LP, Yang YZ, Chen LH, et al. Impact of topical application of autologous platelet]rich gel on medical expenditure and length of stay in hospitals in diabetic patients with refractory cutaneous ulcers. Sichuan Da Xue Xue Bao Yi Xue Ban 2012; 43(5):762-5.
13) Martinez-Zapata MJ, Martí-Carbajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, et al. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev 2016; (5):CD006899.
14) Hu Z, Qu S, Zhang J, Cao X, Wang P, Huang S, et al. Efficacy and safety of platelet-rich plasma for patients with diabetic ulcers: a systematic review and meta-analysis. Adv Wound Care (New Rochelle) 2019; 8(7):298-308. doi:10.1089/wound.2018.0842.
15) Houdek MT, Wyles CC, Stalboerger PG, Terzic A, Behfar A, Moran SL. Collagen and fractionated platelet-rich plasma scaffold for dermal regeneration. Plast Reconstr Surg 2016; 137:1498-1506.
16) Picard F, Hersant B, Bosc R, Meningaud JP. The growing evidence for the use of platelet-rich plasma on diabetic chronic wounds: a review and a proposal for a new standard care. Wound Repair Regen 2015; 23(5):638-43. doi: 10.1111/ wrr.12317.
17) Mohammadi MH, Molavi B, Mohammadi S, Nikbakht M, Mohammadi AM, Mostafaei S, et al. Evaluation of wound healing in diabetic foot ulcer using platelet-rich plasma gel: a single-arm clinical trial. Transfus Apher Sci 2017; 56(2):160-4. doi: 10.1016/j.transci.2016.10.020.
18) Rodriguez AE, Gisbert S, Palazón A, Alio JL. Quantification of growth factors and fibronectin in diverse preparations of platelet-rich plasma for the treatment of ocular surface disorders (E-PRP). Transl Vis Sci Technol 2020; 9(6):22. doi: 10.1167/tvst.9.6.22.
19) Huang Y, Xie T, Cao Y, Wu M, Yu L, Lu S, et al. Comparison of two classification systems in predicting the outcome of diabetic foot ulcers: the Wagner grade and the Saint Elian Wound score systems. Wound Repair Regen 2015; 23(3):379-85. doi: 10.1111/wrr.12289.
20) Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care 2001; 24(1):84-8. doi: 10.2337/diacare.24.1.84.
21) Kontopodis N, Tavlas E, Papadopoulos G, Pantidis D, Kafetzakis A, Chalkiadakis G, et al. Effectiveness of platelet-rich plasma to enhance healing of diabetic foot ulcers in patients with concomitant peripheral arterial disease and critical limb ischemia. Int J Low Extrem Wounds 2016; 15(1):45-51. doi: 10.1177/1534734615575829.
22) Furst G, Gruber R, Tangl S, Zechner W, Haas R, Mailath G, et al. Sinus grafting with autogenous platelet- rich plasma and bovine hidroxyapatite: a histomorfometric study in minipigs. Clin Oral Implants Res 2003; 14:500-8.
23) British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the use of platelets transfusion. Brit J Haematol 2003; 122:10-23.
24) Kalish J, Hamdan A. Management of diabetic foot problems. J Vasc Surg 2010; 51(2):476-86.
25) Veves A, Falanga V, Armstrong DG, Sabolinski ML; Apligraf Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001; 24(2): 290-5.
26) Reyzelman A, Crews RT, Moore JC, Moore L, Mukker JS, Offutt S, et al. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J 2009; 6(3):196- 208.
27) Montón Echeverría J, Pérez Redondo S, Gómez Bajo GJ. Experiencia clínica en el empleo de factores de crecimiento autólogos obtenidos de plasma rico en plaquetas. Cir Plást Iberolatinoam 2007; 33(3):155-62. Disponible en: http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0376-78922007000300002&lng=es.[Consulta: 14 junio 2019].
28) Scimeca CL, Bharara M, Fisher T, Kimbriel H, Armstrong D. Novel use of platelet-rich plasma to augment curative diabetic foot surgery. J Diabetes Sci Technol 2010; 4(5):1121-6.
29) Tzeng YS, Deng SC, Wang CH, Tsai JC, Chen TM, Burnouf T. Treatment of nonhealing diabetic lower extremity ulcers with skin graft and autologous platelet gel: a case series. Biomed Res Int 2013; 2013:837620.
30) Li L, Chen DW, Wang C, Yuan NB, Wang Y, He LP, et al. Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial. Wound Repair Regen 2015; 23(4):495-505.
31) Yuan N, Wang C, Wang Y, Yu T, Long Y, Zhang X, Ran X. Preparation of autologous platelet-rich gel for diabetic refractory dermal ulcer and growth factors analysis from it. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2008; 22(4):468-71.
32) Frykberg RG, Driver VR, Carman D, Lucero B, BorrisHale C, Carelyn P. Chronic wounds treated with a physiologically relevant concentration of plateletrich plasma gel: a prospective case series. Ostomy Wound Manage 2010; 56(6):36-44.
33) Cervelli V, De Angelis B, Lucarini L, Spallone D, Balzani A, Palla L, et al. Tissue regeneration in loss of substance on the lower limbs through use of platelet-rich plasma, stem cells from adipose tissue, and hyaluronic acid. Adv Skin Wound Care 2010; 23(6):262-72.
34) Sakata J, Sasaki S, Handa K, Uchino T, Sasaki T, Higashita R, et al. A retrospective, longitudinal study to evaluate healing lower extremity wounds in patients with diabetes mellitus and ischemia using standard protocols of care and platelet-rich plasma gel in a Japanese wound care program. Ostomy Wound Manage 2012; 58(4):36-49.
35) Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers: a phase III randomized placebo-controlled double-blind study. Diabetes Care 1998; 21:822-7.
36) Gentzkow GD, Iwasaki SD, Hershon KS, Mengel M, Prendergast JJ, Ricotta JJ, Steed DP, Lipkin S. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 1996; 19:350-4.
37) Chen L, Wang C, Liu H, Liu G, Ran X. Antibacterial effect of autologous platelet-rich gel derived from subjects with diabetic dermal ulcers in vitro. J Diabetes Res 2013; 2013:269527.
38) Brigido SA, Schwartz E, McCarroll R, Hardin-Young J. Use of an acellular flowable dermal replacement scaffold on lower extremity sinus tract wounds: a retrospective series. Foot Ankle Spec 2009; 2(2):67-72.
39) Cho JW, Kim SA, Lee KS. Platelet-rich plasma induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts. Int J Mol Med 2012; 29:32-6.
40) Pietramaggiori G, Scherer SS, Mathews JC, Gennaoui T, Lancerotto L, Ragno G, et al. Quiescent platelets stimulate angiogenesis anddiabetic wound repair. J Surg Res 2010; 160:169-77.
41) Dougherty EJ. An evidence-based model comparing the costeffectiveness of platelet-rich plasma gel to alternative therapies for patients with nonhealing diabetic foot ulcers. Adv Skin Wound Care 2008; 21(12):568-75.
42) Kantor J, Margolis DJ. Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness analysis. Dermatologic Surg 2001; 27(4):347-51.
43) International Diabetes Federation; Ibrahim A, Jude E, Langton K, Martinez-De Jesus FR, Harkless LB, Gawish H, et al. IDF Clinical Practice Recommendation on the Diabetic Foot - 2017: a guide for health care professio nals. Brussels: IDF, 2017. Disponible en: https://www. idf.org/e-library/guidelines/119-idf-clinical-practice-recommendations-on-diabetic-foot-2017.html. [Consulta: 14 junio 2019].
44) Martins-Mendes D, Monteiro-Soares M, Boyko EJ, Ribeiro M, Barata P, Lima J, et al. The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk. J Diabetes Complicat 2014; 28(5): 632-8.
45) Steed DL, Edington HD, Webster MW. Recurrence rate of diabetic neurotrophic foot ulcers healed using topical application of growth factors released from platelets. Wound Repair Regen 1996; 4(2):230-3. doi: 10.1046/j.1524-475X. 1996.40210.x.
46) Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care 2001; 24(3):483-8. doi: 10.2337/diacare.24.3.483.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.