Autologous blood concentrates, one of which is platelet-rich plasma, have been becoming more popular as a result of the increasing attention that these products have received in the mainstream media following their use by high-profile athletes. Platelet-rich plasma has been utilized for a number of musculoskeletal conditions despite a relative lack of rigorous supportive data. Thus, there is a growing debate regarding the clinical efficacy of this treatment regimen. Several uncontrolled studies have shown beneficial effects for a variety of indications. However, the results of controlled trials comparing platelet-rich plasma with standard therapies have not been as definitive. Despite this relative lack of robust evidence, the market for platelet-rich plasma is expected to be worth $126 million by 20161.
It is against this backdrop that Sheth et al. provided a timely meta-analysis and systematic review of twenty-three randomized controlled trials and ten prospective cohort studies to assess the clinical results of autologous blood concentrates compared with those of control therapy, such as a placebo, corticosteroid injection, or physical therapy, in the treatment of orthopaedic injuries. Of the 895 eligible studies, thirty-three met the authors’ inclusion criteria, with the investigators in those studies using a variety of primary functional and imaging outcome measures.
The authors found significant heterogeneity in these clinical series as the duration of follow-up ranged from as little as five days to up to two years, and the final volume of platelet product used in each study ranged from just 2 mL to 70 mL. The authors found twenty studies to be of high methodological quality and thirteen studies to be of moderate quality. Nevertheless, there was a lack of consistency in outcome measures across the studies. Of the thirty-three trials, nine showed a significant functional benefit for platelet-rich plasma, twenty-one showed no difference between platelet-rich plasma and the control, and two studies actually revealed a significant functional benefit for the control. (Functional outcomes were not evaluated in the remaining study.) Overall, the authors found no significant benefit for platelet-rich plasma, up to and including twenty-four months, across both the randomized trials and the prospective cohort studies. According to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, a classification scheme based on the strength of clinical recommendations and quality of evidence, the overall quality of evidence was very low because of serious methodological limitations, variability in platelet separation techniques, lack of standardization in outcome measures, and uncertainty surrounding the precision of the results.
In summary, the authors of this well-written, comprehensive study found a significant lack of evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries. Strengths of this study include its rigid inclusion and exclusion criteria, application of a comprehensive search strategy, and use of a quantitative analysis designed to assess the methodological quality of the studies. Interestingly, the published data have shown that platelet-rich plasma, when used alone in various case series, is often effective in terms of decreasing symptoms in a variety of musculoskeletal conditions. Yet, the results of platelet-rich plasma therapy have not been as robust when compared with a standard control. This finding supports the implementation of Level-I randomized controlled trials as the “gold standard” for evidence-based clinical research. My own experience with platelet-rich plasma has been mixed at best, with approximately a 50% improvement in symptom relief noted by patients compared with what would be expected from typical treatment regimens for muscle strains and partial tendon tears.
Despite basic-science data that have demonstrated that platelet-rich plasma use in animal and in vitro studies has a positive effect on healing, there are several issues that remain unanswered regarding the use of this treatment in the care of patients. Questions regarding the timing of platelet-rich plasma administration, optimal platelet concentration and platelet separation technique, ideal volume of the platelet concentrate, number of applications, and duration of the treatment benefit should be addressed in future studies because of the heterogeneous nature of the previously published studies. The authors of future clinical trials should also use validated, disease-specific, and patient-relevant outcomes that can be consistently applied for a variety of similar indications. Until these important issues are adequately addressed, clinicians should temper their enthusiasm for the use of autologous blood products for the treatment of musculoskeletal conditions.