Advertisement
Mayo Clinic Proceedings Home
MCP Digital Health Home

The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds

A Systematic Review and Meta-analysis

      Abstract

      Objective

      To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.

      Patients and Methods

      We searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.

      Results

      We included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events.

      Conclusion

      Autologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers.

      Trial Registration

      PROSPERO Identifier: CRD42020172817

      Abbreviations and Acronyms:

      AE (adverse events), AHRQ (Agency for Healthcare Research and Quality), PAD (peripheral arterial disease), PRP (platelet-rich plasma), RCT (randomized controlled trial), RR (relative risk), SOE (strength of evidence), WMD (weighted mean difference)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Nussbaum S.R.
        • Carter M.J.
        • Fife C.E.
        • et al.
        An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds.
        Value Health. 2018; 21: 27-32
        • Han G.
        • Ceilley R.
        Chronic wound healing: a review of current management and treatments.
        Adv Ther. 2017; 34: 599-610
        • Smiell J.M.
        • Wieman T.J.
        • Steed D.L.
        • Perry B.H.
        • Sampson A.R.
        • Schwab B.H.
        Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies.
        Wound Repair Regen. 1999; 7: 335-346
        • Harrison S.
        • Vavken P.
        • Kevy S.
        • Jacobson M.
        • Zurakowski D.
        • Murray M.M.
        Platelet activation by collagen provides sustained release of anabolic cytokines.
        Am J Sports Med. 2011; 39: 729-734
        • Strandberg G.
        • Sellberg F.
        • Sommar P.
        • et al.
        Standardizing the freeze-thaw preparation of growth factors from platelet lysate.
        Transfusion. 2017; 57: 1058-1065
        • Landesberg R.
        • Burke A.
        • Pinsky D.
        • et al.
        Activation of platelet-rich plasma using thrombin receptor agonist peptide.
        J Oral Maxillofac Surg. 2005; 63: 529-535
        • Drago L.
        • Bortolin M.
        • Vassena C.
        • Taschieri S.
        • Del Fabbro M.
        Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity.
        BMC Microbiol. 2013; 13: 47
        • Cieslik-Bielecka A.
        • Bielecki T.
        • Gazdzik T.S.
        • Arendt J.
        • Król W.
        • Szczepanski T.
        Autologous platelets and leukocytes can improve healing of infected high-energy soft tissue injury.
        Transfus Apher Sci. 2009; 41: 9-12
        • Chadwick P.
        • Edmonds M.
        • McCardle J.
        • Armstrong D.
        Best practice guidelines: Wound management in diabetic foot ulcers.
        Wounds Int. 2014; 5: 27
        • Lavery L.A.
        • Davis K.E.
        • Berriman S.J.
        • et al.
        WHS guidelines update: diabetic foot ulcer treatment guidelines.
        Wound Repair Regen. 2016; 24: 112-126
        • National Institute for Health and Care Excellence
        Diabetic foot problems: prevention and management.
        https://www.nice.org.uk/guidance/ng19
        Date accessed: March 22, 2021
        • Gould L.
        • Stuntz M.
        • Giovannelli M.
        • et al.
        Wound Healing Society 2015 update on guidelines for pressure ulcers.
        Wound Repair Regen. 2016; 24: 145
        • International Guideline
        Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline The International Guideline.
        • Elraiyah T.
        • Tsapas A.
        • Prutsky G.
        • et al.
        A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers.
        J Vasc Sug. 2016; 63: 46S-58S.e41-58S.e42
        • Game F.
        • Jeffcoate W.
        • Tarnow L.
        • et al.
        LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trial.
        Lancet Diabetes Endocrinol. 2018; 6: 870-878
        • Yang L.
        • Gao L.
        • Lv Y.
        • Wang J.
        Autologous platelet-rich gel for lower-extremity ischemic ulcers in patients with type 2 diabetes.
        Int J Clin Exp Med. 2017; 10: 13796-13801
        • Driver V.R.
        • Hanft J.
        • Fylling C.P.
        • Beriou J.M.
        • Autologel Diabetic Foot Ulcer Study Gruop
        A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers.
        Ostomy Wound Manage. 2006; 52 (72, 74 passim): 68-70
        • Burgos-Alonso N.
        • Lobato I.
        • Hernandez I.
        • et al.
        Autologous platelet-rich plasma in the treatment of venous leg ulcers in primary care: a randomised controlled, pilot study.
        J Wound Care. 2018; 27: S20-S24
        • Serra R.
        • Grande R.
        • Butrico L.
        • et al.
        Skin grafting and topical application of platelet gel in the treatment of vascular lower extremity ulcers.
        Acta Phlebologica. 2014; 15: 129-136
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        BMJ. 2009; 339: b2535
        • Sterne J.A.C.
        • Savovic J.
        • Page M.J.
        • et al.
        RoB 2: a revised tool for assessing risk of bias in randomised trials.
        BMJ. 2019; 366: l4898
        • Wells G.
        • Shea B.
        • O’Connell D.
        • et al.
        The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. In: 2000.
        • Rover C.
        • Knapp G.
        • Friede T.
        Hartung-Knapp-Sidik-Jonkman approach and its modification for random-effects meta-analysis with few studies.
        BMC Med Res Methodol. 2015; 15: 99
      1. US Department of Health and Human Services. Agency for Healthcare Research and Quality, ed. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality, Rockville, MDJanuary 2014
        • Li L.
        • Chen D.
        • Wang C.
        • et al.
        Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: a prospective, randomized clinical trial.
        Wound Repair Regen. 2015; 23: 495-505
        • Gude W.
        • Hagan D.
        • Abood F.
        • Clausen P.
        Aurix gel is an effective intervention for chronic diabetic foot ulcers: a pragmatic randomized controlled trial.
        Adv Skin Wound Care. 2019; 32: 416-426
        • Ahmed M.
        • Reffat S.A.
        • Hassan A.
        • Eskander F.
        Platelet-rich plasma for the treatment of clean diabetic foot ulcers.
        Ann Vasc Surg. 2017; 38: 206-211
        • Saad Setta H.
        • Elshahat A.
        • Elsherbiny K.
        • Massoud K.
        • Safe I.
        Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: a comparative study.
        Int Wound J. 2011; 8: 307-312
        • Saldalamacchia G.
        • Lapice E.
        • Cuomo V.
        • et al.
        A controlled study of the use of autologous platelet gel for the treatment of diabetic foot ulcers.
        Nutr Metab Cardiovasc Dis. 2004; 14: 395-396
        • Karimi R.
        • Afshar M.
        • Salimian M.
        • Sharif A.
        • Hidariyan M.
        The effect of platelet rich plasma dressing on healing diabetic foot ulcers.
        Nurs Midwifery Stud. 2016; 5: e30314
        • Kakagia D.D.
        • Kazakos K.J.
        • Xarchas K.C.
        • et al.
        Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial.
        J Diabetes Complications. 2007; 21: 387-391
        • Singh S.P.
        • Kumar V.
        • Pandey A.
        • Pandey P.
        • Gupta V.
        • Verma R.
        Role of platelet-rich plasma in healing diabetic foot ulcers: a prospective study.
        J Wound Care. 2018; 27: 550-556
        • Elsaid A.
        • El-Said M.
        • Emile S.
        • Youssef M.
        • Khafagy W.
        • Elshobaky A.
        Randomized controlled trial on autologous platelet-rich plasma versus saline dressing in treatment of non-healing diabetic foot ulcers.
        World J Surg. 2020; 44: 1294-1301
        • Xie J.
        • Fang Y.
        • Zhao Y.
        • Cao D.
        • Lv Y.
        Autologous platelet-rich gel for the treatment of diabetic sinus tract wounds: a clinical study.
        J Surg Res. 2020; 247: 271-279
        • Milek T.
        • Baranowski K.
        • Zydlewski P.
        • Ciostek P.
        • Mlosek K.
        • Olszewski W.
        Role of plasma growth factor in the healing of chronic ulcers of the lower legs and foot due to ischaemia in diabetic patients.
        Postepy Dermatol Alergol. 2017; 34: 601-606
        • Glukhov A.A.
        • Aralova M.V.
        The study of the effectiveness of the drug combination of collagen and platelet-rich plasma for the regional treatment of venous ulcers.
        Res J Pharm Biol Chem Sci. 2017; 8: 2258-2263
        • Senet P.
        • Bon F.X.
        • Benbunan M.
        • et al.
        Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers.
        J Vasc Surg. 2003; 38: 1342-1348
        • Escamilla Cardenosa M.
        • Dominguez-Maldonado G.
        • Cordoba-Fernandez A.
        Efficacy and safety of the use of platelet-rich plasma to manage venous ulcers.
        J Tissue Viability. 2017; 26: 138-143
        • Milek T.
        • Nagraba L.
        • Mitek T.
        • et al.
        Autologous platelet-rich plasma reduces healing time of chronic venous leg ulcers: a prospective observational study.
        Adv Exp Med Biol. 2019; 1176: 109-117
        • Etugov D.
        • Mateeva V.
        • Mateev G.
        Autologous platelet-rich plasma for treatment of venous leg ulcers: a prospective controlled study.
        J Biol Regul Homeost Agents. 2018; 32: 593-597
        • Elbarbary A.H.
        • Hassan H.A.
        • Elbendak E.A.
        Autologous platelet-rich plasma injection enhances healing of chronic venous leg ulcer: a prospective randomised study.
        Int Wound J. 2020; 17: 992-1001
        • Yuvasri G.
        • Rai R.
        Comparison of efficacy of autologous platelet-rich fibrin versus unna's paste dressing in chronic venous leg ulcers: a comparative study.
        Indian Dermatol. 2020; 11: 58-61
        • Moneib H.A.
        • Youssef S.S.
        • Aly D.G.
        • Rizk M.A.
        • Abdelhakeem Y.I.
        Autologous platelet-rich plasma versus conventional therapy for the treatment of chronic venous leg ulcers: a comparative study.
        J Cosmet Dermatol. 2018; 17: 495-501
        • Ucar O.
        • Celik S.
        Comparison of platelet-rich plasma gel in the care of the pressure ulcers with the dressing with serum physiology in terms of healing process and dressing costs.
        Int Wound J. 2020; 17: 831-841
        • Singh R.
        • Rohilla R.K.
        • Dhayal R.K.
        • Sen R.
        • Sehgal P.K.
        Role of local application of autologous platelet-rich plasma in the management of pressure ulcers in spinal cord injury patients.
        Spinal Cord. 2014; 52: 809-816
      2. National Health Service. National Diabetes Foot Care Audit, 2014-2018.
        (Published 2019. Updated January 8, 2020. Accessed May 9, 2019)
        • Margolis D.J.
        • Kantor J.
        • Berlin J.A.
        Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis.
        Diabetes Care. 1999; 22: 692-695
        • Ndosi M.
        • Wright-Hughes A.
        • Brown S.
        • et al.
        Prognosis of the infected diabetic foot ulcer: a 12-month prospective observational study.
        Diabet Med. 2018; 35: 78-88
        • Sheehan P.
        • Jones P.
        • Caselli A.
        • Giurini J.M.
        • Veves A.
        Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial.
        Diabetes Care. 2003; 26: 1879-1882
        • Bus S.A.
        Priorities in offloading the diabetic foot.
        Diabetes Metab Res Rev. 2012; 28: 54-59
        • Meijer J.W.G.
        • Trip J.
        • Jaegers S.M.H.J.
        • et al.
        Quality of life in patients with diabetic foot ulcers.
        Disability Rehab. 2001; 23: 336-340
        • Roth R.S.
        • Lowery J.C.
        • Hamill J.B.
        Assessing persistent pain and its relation to affective distress, depressive symptoms, and pain catastrophizing in patients with chronic wounds: a pilot study.
        Am J Phys Med Rehabil. 2004; 83: 827-834
        • Werneke M.
        • Hart D.L.
        Centralization phenomenon as a prognostic factor for chronic low back pain and disability.
        Spine (Phila Pa 1976. 2001; 26: 758-764
        • Lindholm C.
        • Bjellerup M.
        • Christensen O.B.
        • Zederfeldt B.
        Quality of life in chronic leg ulcer patients. An assessment according to the Nottingham Health Profile.
        Acta Derm Venereol. 1993; 73: 440-443
        • Ribu L.
        • Rustoen T.
        • Birkeland K.
        • Hanestad B.R.
        • Paul S.M.
        • Miaskowski C.
        The prevalence and occurrence of diabetic foot ulcer pain and its impact on health-related quality of life.
        J Pain. 2006; 7: 290-299
        • Paschou S.A.
        • Stamou M.
        • Vuagnat H.
        • Tentolouris N.
        • Jude E.
        Pain management of chronic wounds: Diabetic ulcers and beyond.
        Maturitas. 2018; 117: 17-21
        • Volkow N.D.
        • McLellan A.T.
        Opioid abuse in chronic pain—misconceptions and mitigation strategies.
        N Engl J Med. 2016; 374: 1253-1263
        • Mahdavian Delavary B.
        • van der Veer W.M.
        • van Egmond M.
        • Niessen F.B.
        • Beelen R.H.
        Macrophages in skin injury and repair.
        Immunobiology. 2011; 216: 753-762
        • Hofman D.
        • Ryan T.J.
        • Arnold F.
        • et al.
        Pain in venous leg ulcers.
        J Wound Care. 1997; 6: 222-224
        • Vilela L.
        • Salomé G.
        • Pereira R.
        • Ferreira L.
        Pain assessment in patients with venous leg ulcer treated by compression therapy with unnas boot.
        J Tissue Sci Eng. 2016; 7: 2