Need for Proper Classification of PRP: Letter to the Editor.

Dear Editor: It was with great interest that we reviewed the article by Cole et al published in the American Journal of Sports Medicine. More than a decade has passed since the initial use of platelet-rich plasma (PRP) for orthopaedic conditions, and controversies continue as to whether this treatment is effective for various conditions including chronic tendinopathy, ligament injuries, and articular cartilage lesions. As noted in the literature, a great deal of this controversy is related to the lack of standardization of what we refer to as ‘‘PRP.’’ As the science of PRP evolves, it has become apparent that not all PRP processing systems yield the same parameters, and final PRP injectates vary greatly. Due to these variations in PRP, terminology and classification have become imperative, and the most updated classification system has attempted to quantify PRP and determine appropriate dosing to improve objective outcome measures. From a biological standpoint, the characterization of the presence of cells (such as leukocytes) is a critical step, but many other parameters should be considered, such as the rate and quantity of platelet collection, the rate and quantity of leukocyte collection, and detailed composition of the cells during collection and centrifugation. The activation of the cell content during or after centrifugation is also important for the biological properties of these products. Other technical parameters should be considered as well, because they directly affect the possibility of using these techniques in daily clinical practice: These parameters include the size of the centrifuge; the duration, cost, and ergonomic properties of the preparation procedure; the final volume of product; and its form (liquid, light gel, or solid gel material). Although the study by Cole et al provides valuable data on PRP, the study fails to quantify the type of PRP used through any other classification system. The article fails to appropriately describe the dose of PRP provided (ie, the actual platelet count), which is a major flaw of the study. According to the data provided in the article, the platelet concentration is less than 2 times the baseline concentration of platelets in all the subjects injected. Given the normal range of platelet concentration in the average population of 100,000 to 400,000/mL, the subjects in this study would have received platelet concentrations of anywhere from 200,000 to 800,000/mL. This would be considered a low platelet concentration for the treatment of primary knee osteoarthritis given that other studies have demonstrated the efficacy of PRP at concentrations greater than 5 times the baseline. Another parameter that adds to the variability of PRP is the spin time. Cole et al chose a spin time of 5 minutes, which is less than the time supported by current practice and literature. The authors provide excellent background on the hyaluronic acid dosing profile but do not provide a proper dosing profile for the PRP arm; the novice reader looking at the title and conclusions of the study would thus be misled. The authors did not clarify whether their 3-mL blood draw was made through the same venous access as the 10-mL port for PRP preparation, thus not accurately accounting for platelet discrepancy. The report of the 2015 AOSSM Biologics Think Tank outlined that while PRP holds promise, 2 particular challenges must be met in order to advance the science: characterizing active elements in PRP injectate and finding the appropriate dosing regimen. The cytokine profile chosen by Cole et al was novel compared with profiles reported in the current PRP literature; however, only 2 of 10 catabolic parameters showed significance at one time point, and the paper did not disclose the variability in analysis of 2 mL of synovial sample. A wider panel of anabolic chemokines would have added valuable information in the context of anabolic-catabolic ratio. The study by Cole et al adds to the growing body of evidence regarding the safety profile of PRP. The paper highlights that this particular PRP product failed to show significance in the primary outcome (ie, Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain scale); however, multiple study endpoints demonstrated statistically significant differences and showed superiority of even this low-dose PRP product compared with hyaluronic acid, including reductions in visual analog scale (VAS) pain score and International Knee Documentation Committee (IKDC) knee evaluation scores at 24 and 52 weeks. Like several other studies examining PRP, the study by Cole et al is a prospective, double-blind, randomized controlled trial whose design appears to be at the highest level of science; however, the actual PRP product lacks an up-todate characterization. Thus, this article fails to advance the science regarding the PRP product used, its effect on osteoarthritis compared with hyaluronic acid, and its effect on various important synovial biochemical constituents found in patients who have osteoarthritis. We encourage the editors of AJSM and other journals of high scientific quality to require strict characterization of the PRP content prior to acceptance of future articles on this topic. This will greatly assist readers in properly assessing the scientific evidence of this treatment.