Regarding “Comparison of Conventional Dose Versus Superdose Platelet-Rich Plasma for Knee Osteoarthritis”

Dear Editor,

We have read with interest the paper by Patel et al, ⁵ titled “Comparison of conventional dose versus superdose platelet-rich plasma for knee osteoarthritis.” In their work, the authors conducted a clinical trial comparing the administration of different volumes of platelet-rich plasma (PRP) in patients with knee osteoarthritis, focusing on the importance of platelet dose.

Studies of this kind are of great importance in differentiating the several PRP-based treatments and optimizing the application protocols, thus marking the lines of research to be followed in the future. However, despite the commendable effort made by the authors, this work presents some limitations that must be highlighted to avoid drawing misleading conclusions. In our opinion, apart from the flaws in the study identified by both authors and by Poyraz, ⁶ the conclusion reached cannot be drawn from this conceptualization and design.

In this paper, the authors compare the application of 2 different volumes of PRP (4 mL and 8 mL) with the same platelet concentration, so that one group of patients receives twice the platelet dose as the other. Both groups of patients report an improvement after treatment, with the improvement being greater in patients who received 8 mL of PRP. The authors attribute this superiority to a higher platelet dose, which is either false or at least cannot be demonstrated in this study.

First, in addition to receiving a higher platelet dose, these patients also received twice the volume; thus, the effect of both variables cannot be isolated. The analysis and interpretation of the results ignore or underestimate the potential impact of the administered volume on the patient's response. The application of an appropriate PRP volume would condition a correct distribution of its contents, in this case, in the knee joint space. Other studies that have already addressed this issue suggest the application of high volumes in this joint.^2,7 It is also important to note that, according to Table 3 of this work, ⁵ there are no significant differences between the dose of administered platelets, which seems to us to be erroneous and should be corrected by the authors.

Second, the effect of PRP cannot be attributed solely to platelets. Although platelets are undoubtedly a crucial element in this product, there are a large number of extra-platelet components with biological activity that could contribute to the action of PRP. ⁸ Growth factors such as insulin-like growth factor 1 or fibroblast growth factor-basic are independent of platelet concentration.^1,3 In addition, other elements such as cytokines, molecules such as alpha-2-macroglobulin, or extracellular vesicles are also found circulating free in the plasma, which have generated great interest in orthobiology.^4,9

Therefore, the administration of a higher application volume not only results in a higher platelet count but also a higher distribution and a higher dose of other biologically active components. If the authors aimed to analyze platelet dose only, they should have applied the same volume in both groups, but with different platelet concentrations (one twice as high as the other). This method would have isolated the effect of the platelet count administered.

Although such studies are necessary to advance the understanding and improvement of orthobiology, accurate study design and analysis are essential for preventing incorrect conclusions and misleading future studies.

Mikel Sánchez, MD, PhD Diego Delgado, PhD MiKS Hospital, Vitoria-Gasteiz, Spain