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Editorial Commentary: Leukocyte-Poor Platelet-Rich Plasma Decreases Retear Rate in Arthroscopic Rotator Cuff Repair: Platelet-Rich Plasma Type Matters

      Abstract

      Numerous studies, including several meta-analysis reviews of platelet-rich plasma (PRP) in the setting of arthroscopic rotator cuff repair, show mixed results. Focusing on specific types of PRP configuration may elucidate which provide value and which do not. Recent meta-analysis demonstrates that leukocyte-poor PRP or “pure PRP” treatment is shown to decrease retear rate and patient-reported outcome measures after arthroscopic rotator cuff repair of the shoulder. Meta-analyses resulting in conflicting results may be attributed to different study inclusion and exclusion criteria and date of search.
      There is now a plethora of meta-analysis articles describing results of platelet-rich plasma (PRP) to augment rotator cuff repairs (RCRs). At this point, while it seems that the jury is still out on PRP, the challenge lies in understanding PRP formulations and what type of PRP to use on what specific problem. We know not all PRP is the same. Ryan, Imbergamo, Sudah, Kirchner, Greenberg, Monica, and Gatt
      • Ryan J.
      • Imbergamo C.
      • Sudah S.
      • Kirchner G.
      • Greenberg P.
      • Monica J.
      • Gatt C.
      Platelet-rich product supplementation in rotator cuff repair reduces retear rates and improves clinical outcomes: A meta-analysis of randomized controlled trials.
      in “Platelet-Rich Product Supplementation in Rotator Cuff Repair Reduces Retear Rates and Improves Clinical Outcomes: A Meta-analysis of Randomized Controlled Trials” focused on the type of PRP configuration. They differentiated between 4 classifications of PRP: pure platelet-rich plasma (P-PRP), leukocyte- and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), and leukocyte- and platelet-rich fibrin (L-PRF) referencing the work by Ehrenfest et al.
      • 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.
      in 2014.
      While the meta-analysis did not explore further differentiation, Ryan et al.
      • Ryan J.
      • Imbergamo C.
      • Sudah S.
      • Kirchner G.
      • Greenberg P.
      • Monica J.
      • Gatt C.
      Platelet-rich product supplementation in rotator cuff repair reduces retear rates and improves clinical outcomes: A meta-analysis of randomized controlled trials.
      suggested that the fibrin type of PRP may have had a greater failure rate due to interposition of tissue between the tendon−bone interface of the RCR. Conversely, the leukocyte-poor liquid PRP, described as “pure PRP (P-PRP)” in Ryan et al., does not displace tissue when infiltrated in the interface of tendon and bone. The RCRs performed with P-PRP in the meta-analysis succeeded more often in achieving repair of the tendon compared with other configurations of PRP.
      Critically, even within the 4 different categories of PRP studies, there are different concentrations of platelets, different volumes of PRP injection, and other factors that make it difficult to create a homogenous group of PRP subgroups. Because the idea of PRP has expanded so much in the past 10 years or so, it is very difficult to know which PRP mix is best in which situation. One of the values of the study by Ryan et al. is that they only evaluated arthroscopic RCR and no other pathology and only used studies that had postoperative imaging to assess the repair integrity instead of only using patient-reported outcome measures.
      Adding to the PRP controversy is a recent study by Li et al.
      • Li M.
      • Wang K.
      • Zhang H.
      • Fang C.
      • Liu H.
      • Zhang Y.
      Clinical evaluations of intraoperative injection of platelet-rich plasma in arthroscopic single-row rotator cuff repair at 2-year follow-up.
      that similarly found a lower retear rate at 2-year follow-up after RCR in small- and medium-sized tears augmented with PRP. Yet, they used a leukocyte-rich PRP with >6× platelet and leukocyte concentration. There was no difference in UCLA and Constant scores at 3, 6, or 24 months’ postoperatively but the smaller retear rate was significant.
      Several recent meta-analyses focused on the efficacy of PRP to augment RCRs have been recently published. While the results are mixed, a deeper dive into why PRP may or may not work to improve healing is warranted.
      Yang et al.
      • Yang J.
      • Sun Y.
      • Xu P.
      • Cheng B.
      Can patients get better clinical outcomes by using PRP in rotator cuff repair: A meta-analysis of randomized controlled trials.
      performed a meta-analysis of 8 studies, all of which were included in this study by Ryan et al. In contrast to the present study, Yang et al. did not find a difference in healing after RCR with the addition of PRP. However, with the 9 additional studies included, the present meta-analysis resulted in a significant difference in healing rates identified.
      Another recent meta-analysis reviewed 7 randomized controlled trials published from 2013 to 2018 with 541 patients included. The results revealed a significant decrease in retear rate and a short-term improvement in Constant, UCLA, and visual analog scale scores. This systematic review indicated the efficacy of PRP when applied to the bone–tendon interface during arthroscopic RCR.
      • Yang F.-A.
      • Wu C.-W.
      • Shih Y.-C.
      • Wu L.-C.
      • Chen H.-C.
      Effects of applying platelet-rich plasma during arthroscopic rotator cuff repair: A systematic review and meta-analysis of randomized controlled trials.
      A larger meta-analysis performed by Hurley et al.
      • Hurley E.T.
      • Lim Fat D.
      • Moran C.J.
      • Mullett H.
      The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: A meta-analysis of randomized controlled trials.
      and referenced by Ryan et al.
      • Ryan J.
      • Imbergamo C.
      • Sudah S.
      • Kirchner G.
      • Greenberg P.
      • Monica J.
      • Gatt C.
      Platelet-rich product supplementation in rotator cuff repair reduces retear rates and improves clinical outcomes: A meta-analysis of randomized controlled trials.
      included 18 randomized controlled trials with 1147 patients comparing PRP and PRF. PRP resulted in significantly decreased rates of incomplete tendon healing for all tears including small-to-medium tears as well as medium-to-large tears. There was a significant result in favor of PRP for the Constant and visual analog scale score for pain at 30 days postoperatively and at final follow-up. PRF did not result in a significantly decreased rate of incomplete tendon healing for all tears combined or an improved Constant score. In addition, PRF resulted in a significantly longer operation time compared with the control. This study indicated that the use of PRP in RCR results in improved healing rates, pain levels, and functional outcomes. In contrast, PRF had no benefit in improving tendon healing rates or functional outcomes.
      • Hurley E.T.
      • Lim Fat D.
      • Moran C.J.
      • Mullett H.
      The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: A meta-analysis of randomized controlled trials.
      Di Zhao et al.
      • Di Zhao Y.-H.
      • Han J.-K.
      • Pan W.-Y.
      • Yang L.-F.
      • Zeng G.-H.
      • Liang J.L.
      The clinical efficacy of leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair: A meta-analysis of randomized controlled trials.
      performed a meta-analysis investigating leukocyte-poor PRP to evaluate whether PRP promotes and improves the effects of arthroscopic RCR. Ten randomized controlled trials involving 742 patients were included. They determined that leukocyte-poor PRP reduced the postoperative retear rate in the medium and long term regardless of the tear size and the method used for RCR (single-row repair or double-row suture bridge repair). In their analysis, the use of leukocyte-poor PRP improved postoperative pain and patient-reported outcome measures but failed to improve beyond the minimal clinically important difference.
      So why is another PRP meta-analysis important? Ryan et al. has helped us consolidate our understanding in which RCR cases PRP may be helpful. More importantly, a liquid form of leukocyte-poor PRP applied at the bone−tendon interface likely provides a benefit in improving rotator cuff tendon repair healing.

      Supplementary Data

      References

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