Cite as: Kanuri SH, Maoli F, Eshraghi Y, Buchheit T. Optimizing PRP therapy: can platelet-rich plasma characteristics predict treatment outcomes for knee osteoarthritis. ASRA Pain Medicine News 2025;50. https://doi.org/10.52211/asra020125.009.

Osteoarthritis (OA) is a prevalent and debilitating degenerative joint disease that affects over 30 million Americans.¹ Traditional pharmacologic treatments, such as NSAIDs and corticosteroids, can provide symptom improvement but often have side effects.² Hyaluronic acid injections may provide longer-term pain relief for some patients, but the analgesic and functional gains are often limited.³ Geniculate radiofrequency ablation may be an option for patients with more advanced OA. Still, it is considered experimental by some insurance carriers despite evidence demonstrating improved function and quality of life. This limitation reduces its accessibility. These treatment gaps have prompted the search for more enduring interventions.

In recent years, biologically based therapies such as platelet-rich plasma (PRP) have gained increasing traction for the treatment of musculoskeletal conditions, including OA. Although PRP has been promoted as an effective therapy for mild to moderate knee OA,⁴ several large, negative clinical trials refute that claim.^5,6 Understanding these contradictory research findings in the treatment of OA is difficult, given the numerous devices currently available to create PRP, each with widely varying output characteristics.⁷ Although several ASRA Pain Medicine Regenerative Medicine SIG members have written about the importance of publishing product characteristics for PRP,⁸ a standard classification and reporting system has yet to be widely adopted.⁹ The term “PRP” describes a range of products from 8-10 times baseline platelet concentrations to those with platelet counts in the physiologic range.¹⁰ Likewise, PRP may contain high concentrations of leukocytes or be nearly depleted of these immune cells. These inconsistencies make it difficult for the practitioners to decide on optimal PRP processing methods for the patient and the condition treated.¹¹

To gain better insight into the characteristics of PRP products and factors contributing to treatment success, we selected eight representative publications of PRP for OA (four positive trials and four negative trials). We only selected publications that were prospective, randomized, blinded trials with a single intervention control arm. We excluded combination interventions (eg, PRP with hyaluronic acid, comparative effectiveness trials, and other trial designs) from the review. After extensive discussions, the authors also included a PRP trial for treating ankle OA.⁶ The high-profile nature of the study, the authors’ conclusions that PRP is ineffective for OA, and the lack of scrutiny regarding platelet counts in subsequent letters to the editor of JAMA¹² necessitated the inclusion of this publication in our discussion. We reviewed the platelet concentrations, leukocyte counts, and number of injections in the trials and noted characteristics associated with PRP intervention's success (or failure) (Tables 1 and 2).

Discussion

Over the past decade, our understanding of OA has evolved as a complex immunologic disorder characterized by alterations in cytokine and growth factor expression.²⁰ PRP, an autologous blood product enriched with these bioactive components, has emerged as a potential treatment to promote cartilage health and produce analgesia.²¹ However, PRP and related biologic therapies are not panaceas. These products need to be scrutinized for optimal outcomes. Standard preparation protocols should be established along with internationally accepted criteria for what defines PRP.

In our four representative positive clinical trials of PRP, all contained platelet concentrations of 3X or greater when compared with patients’ baseline.^13-16 The four negative studies we reviewed share a common characteristic of having lower platelet concentrations (between approximately 1.2-1.7X of baseline).^5,6,18,19 These clinical outcomes are consistent with laboratory research demonstrating the need for robust concentrations of growth factors to promote healing, tissue repair, and the resolution of pain.^22,23 Studies have indicated that optimal tissue regeneration responses are likely achieved when platelet concentrations range from 1 to 1.5 × 10^6 platelets/microliter,^24,25 well above the 1.2-1.7X concentrations noted in these four negative trials.

Another factor that we reviewed in the eight studies was leukocyte concentration. PRP is generally categorized as leukocyte-rich (white blood cell count above baseline) or leukocyte-poor (below baseline). The impact of leukocytes on PRP has been controversial. Pre-clinical and clinical research shows that higher leukocyte concentrations can promote acute inflammation and elevations of catabolic cytokines such as IL-1 and TNF-α.²⁶ These concerns over inflammatory response have prompted some recommendations for leukocyte-poor PRP (LP-PRP) to treat knee osteoarthritis, thereby minimizing pain and inflammation from the procedure.²⁷

Studies that use PRP with at least 3X concentration appear to be more successful in producing analgesia for patients with osteoarthritis.

Those recommendations for LP-PRP products, however, have not gone without criticism. Leukocytes are also known to stimulate cell proliferation and tissue repair.²⁸ Research by Ehrenfest et al. demonstrated that neutrophils stimulate platelets to release growth factors. They saw enhanced chondrocyte proliferation in animal models of OA treated with PRP enriched with leukocytes.^29,30 The importance of leukocytes in PRP, therefore, remains debated. In the four negative PRP studies, all were leukocyte-reduced products. In the four positive PRP studies, leukocyte concentrations were variable. It remains challenging to draw conclusions from these data other than to note that leukocyte concentrations in PRP do not appear as critical for success as platelet enrichment.

The optimal number of PRP intra-articular (IA) injections remains unclear from our sample publications. In three studies^14–16, a single PRP IA injection was administered, and four studies ^5,13,18,19 provided three weekly IA injections. In one study,¹⁴ injections were given every three weeks; in another study,⁶ the injections were spaced six weeks apart. Several negative studies used multiple injections, and two positive studies used only one. These data lead us to surmise that the characteristics of the injected PRP are likely more important than the number of injections for achieving successful outcomes.

More detailed reporting on PRP characteristics in these and similar clinical studies needs to be done. Minimal Information for Studies Evaluating Biologics in Orthopedics guidelines have been proposed, including study design, intervention, blood characteristics, PRP characteristics, processing, and outcomes. In a recent meta-analysis of PRP studies, it was noted that almost 50% of studies do not adhere to these guidelines.³¹ Inadequate reporting leads to difficulty in interpreting (and reproducing) research. These limitations were highlighted in a systematic review by Chahla et al., which found that out of 105 studies using PRP in orthopedics, only 11 provided comprehensive reporting of the PRP preparation protocol usable by subsequent researchers. Further, only 17 studies offered qualitative metrics on the composition of their PRP.³² Product information is needed to effectively compare, replicate, and validate findings.

Conclusion

Our review of eight studies of PRP for OA, including calculations of platelet concentrations from primary and supplemental data sources, highlights a clear relationship between platelet concentration and clinical trial success. The four positive trials reported platelet counts of 3X or greater over baseline. The negative trials showed lower platelet concentrations ranging from 1.2-1.7X above baseline. Although this analysis is not a systematic review of the literature, the observed trend of these eight studies suggests a potential threshold for therapeutic efficacy. The impact of leukocyte concentration and the number of injections appear less consistently associated with successful outcomes. We look forward to future research to better define the optimal PRP characteristics for OA and other degenerative conditions, which could pave the way for more disease-specific, standardized treatment protocols.

References

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