Author reply to “Regarding ‘Meta-analysis Comparing Autologous Blood-Derived Products (Including Platelet-Rich Plasma) Injection Versus Placebo in Patients With Achilles Tendinopathy”’
Journal
Arthroscopy - Journal of Arthroscopic and Related Surgery
Journal Volume
34
Journal Issue
9
Pages
2528-2529
Date Issued
2018
Author(s)
Abstract
We wholeheartedly appreciate the recent correspondence by Shimozono, Hurley, Fortier, and Kennedy regarding our article1Lin M.T. Chiang C.F. Wu C.H. Hsu H.H. Tu Y.K. Meta-analysis comparing autologous blood-derived products (including platelet-rich plasma) injection versus placebo in patients with Achilles tendinopathy.Arthroscopy. 2018; 34: 1966-1975Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar and welcome this opportunity to address their thoughtful comments. This correspondence provides valuable insight regarding the complexity of treatments with autologous blood-derived products (ABPs), including concentration of leukocytes and platelets, injection sites and methods, and adjuvant medications. We agree with Shimozono et al. that it’s necessary to standardize the preparation of ABPs (including platelet-rich plasma [PRP]) and reporting of contents including platelet number, leukocyte concentration, growth factors and progenitor cells presence.2Dohan Ehrenfest D.M. Andia I. Zumstein M.A. Zhang C.Q. Pinto N.R. Bielecki T. Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: Current consensus, clinical implications and perspectives.Muscles Ligaments Tendons J. 2014; 4: 3-9Crossref PubMed Google Scholar, 3Chahla J. Cinque M.E. Piuzzi N.S. et al.A call for standardization in platelet-rich plasma preparation protocols and composition reporting: A systematic review of the clinical orthopaedic literature.J Bone Joint Surg Am. 2017; 99: 1769-1779Crossref PubMed Scopus (230) Google Scholar Nevertheless, none of seven included randomized controlled trials (RCTs) reported the contents of ABPs, which hindered us from conducting further subgroup analysis and meta-regression. We thought that it was inappropriate to stratify subgroups without the detailed composition (numbers of platelets and leukocytes) of ABPs. Although there was no significant heterogeneity detected among the included RCTs by Cochran Q and I2 methods, we believe heterogeneity did exist in preparation and contents of ABPs, injection sites, guidance methods, and cointerventions such as eccentric exercise. Aforementioned factors raised a risk of masking the effects of ABPs to a different extent in each study and were exactly inherent limitations in systematic reviews and meta-analysis. In this correspondence, Shimozono et al. point out that inferiority of leukocyte-rich PRP (Lr-PRP) to leukocyte-poor PRP (Lp-PRP)4Rubio-Azpeitia E. Bilbao A.M. Sanchez P. Delgado D. Andia I. The properties of 3 different plasma formulations and their effects on tendinopathic cells.Am J Sports Med. 2016; 44: 1952-1961Crossref PubMed Scopus (34) Google Scholar, 5Yan R. Gu Y. Ran J. et al.Intratendon delivery of leukocyte-poor platelet-rich plasma improves healing compared with leukocyte-rich platelet-rich plasma in a rabbit Achilles tendinopathy model.Am J Sports Med. 2017; 45: 1909-1920Crossref PubMed Scopus (67) Google Scholar may lead to the negative results in this meta-analysis, because most included studies used Lr-PRP,6de Vos R.J. Weir A. van Schie H.T. et al.Platelet-rich plasma injection for chronic Achilles tendinopathy: A randomized controlled trial.JAMA. 2010; 303: 144-149Crossref PubMed Scopus (645) Google Scholar, 7de Jonge S. de Vos R.J. Weir A. et al.One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: A double-blind randomized placebo-controlled trial.Am J Sports Med. 2011; 39: 1623-1629Crossref PubMed Scopus (275) Google Scholar, 8Kearney R.S. Parsons N. Costa M.L. Achilles tendinopathy management: A pilot randomised controlled trial comparing platelet-rich plasma injection with an eccentric loading programme.Bone Joint Res. 2013; 2: 227-232Crossref PubMed Scopus (60) Google Scholar, 9Krogh T.P. Ellingsen T. Christensen R. Jensen P. Fredberg U. Ultrasound-guided injection therapy of Achilles tendinopathy with platelet-rich plasma or saline: A randomized, blinded, placebo-controlled trial.Am J Sports Med. 2016; 44: 1990-1997Crossref PubMed Scopus (88) Google Scholar whereas only one used Lp-PRP.10Boesen A.P. Hansen R. Boesen M.I. Malliaras P. Langberg H. Effect of high-volume injection, platelet-rich plasma, and sham treatment in chronic midportion Achilles tendinopathy: A randomized double-blinded prospective study.Am J Sports Med. 2017; 45: 2034-2043Crossref PubMed Scopus (132) Google Scholar First, the superiority of Lp-PRP shown in an in vitro study4Rubio-Azpeitia E. Bilbao A.M. Sanchez P. Delgado D. Andia I. The properties of 3 different plasma formulations and their effects on tendinopathic cells.Am J Sports Med. 2016; 44: 1952-1961Crossref PubMed Scopus (34) Google Scholar and an animal study5Yan R. Gu Y. Ran J. et al.Intratendon delivery of leukocyte-poor platelet-rich plasma improves healing compared with leukocyte-rich platelet-rich plasma in a rabbit Achilles tendinopathy model.Am J Sports Med. 2017; 45: 1909-1920Crossref PubMed Scopus (67) Google Scholar does not indicate the same results in human studies. Second, in the human RCT using Lp-PRP, the PRP group showed favorable outcome to placebo only at 24-week follow-up but not at 6- and 12-week follow-up; furthermore, after data synthesis in the meta-analysis, the weighted mean difference was insignificant as 10.8 (95% confidence interval: –0.13 to 21.73). Based on the current evidence, it may be too early to say whether Lp-PRP or Lr-PRP is better in clinical practice. The negative results in this meta-analysis may also raise an important issue regarding distinctive characteristics of the Achilles tendon, including weight-loading tendon, limited blood supply, surrounded by the paratenon without true synovial sheath.11Kader D. Saxena A. Movin T. Maffulli N. Achilles tendinopathy: Some aspects of basic science and clinical management.Br J Sports Med. 2002; 36: 239-249Crossref PubMed Scopus (296) Google Scholar, 12Maffulli N. Sharma P. Luscombe K.L. Achilles tendinopathy: Aetiology and management.J R Soc Med. 2004; 97: 472-476Crossref PubMed Scopus (249) Google Scholar Effects of ABPs on the Achilles tendon may differ from other commonly studied tendons, such as rotator cuff tendons and common extensor tendons of the elbow. The conclusion of this meta-analysis was based on the currently available human RCTs. Several limitations did exist and we had addressed them in our manuscript. There is a paucity of clinical research comparing the effectiveness of various ABPs (such as Lr-PRP, Lp-PRP, platelet-poor plasma, and autologous blood) to the placebo or to one another on Achilles tendinopathy. We hope more and more high-quality RCTs will be conducted and lead us to the optimal management of Achilles tendinopathy. Download .pdf (.16 MB) Help with pdf files ICMJE author disclosure forms Regarding “Meta-analysis Comparing Autologous Blood-Derived Products (Including Platelet-Rich Plasma) Injection Versus Placebo in Patients With Achilles Tendinopathy”ArthroscopyVol. 34Issue 9PreviewWe read with interest the article entitled “Meta-analysis Comparing Autologous Blood-Derived Products (Including Platelet-Rich Plasma) Injection Versus Placebo in Patients With Achilles Tendinopathy” by Lin, Chiang, Wu, Hsu, and Tu.1 The authors analyzed the data from 6 randomized controlled trials and a subgroup of 229 patients through a random effects meta-analysis. The authors concluded that autologous blood-derived products, including platelet-rich plasma (PRP), were not more effective as a treatment for Achilles tendinopathy than placebo. Full-Text PDF
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Publisher
W.B. Saunders
Type
letter