Clinical effectiveness of platelet-rich plasma (PRP) for knee osteoarthritis (OA) continues to be debated, largely due to inconsistencies in PRP preparation methods and the variability in platelet concentrations. The optimal therapeutic range for platelet concentration remains unclear, leading to inconsistent treatment protocols and outcomes across studies. This systematic review and meta-analysis aimed to evaluate whether platelet count in PRP influences clinical outcomes in patients with knee OA.

A systematic search was conducted in MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials through February 2024. Randomized controlled trials evaluating PRP injections in knee OA were included. Studies reporting platelet counts in whole blood and PRP, as well as baseline and follow-up pain and functional scores, were analyzed. Standardized mean differences (SMD) were computed, and subgroup analyses were conducted based on platelet fold increase in PRP preparation.

Forty studies met the inclusion criteria. PRP improved both pain and function across all platelet concentration categories. However, lower platelet fold increases (0−2× and >2−4×) demonstrated greater clinical benefits (SMD 1.84, 95% CI [1.05, 2.04], p = 0.0004 and SMD 1.36, 95% CI [0.94, 1.79], p < 0.0001, respectively) compared to higher concentrations (>4−6× and >6−9×). Effect sizes for lower concentrations exceeded established minimal clinically important differences.

Moderate platelet count increases (2−4×) in PRP appear optimal for knee OA treatment. Higher platelet concentrations may not provide additional benefit and could attenuate therapeutic effects. These findings highlight the importance of standardizing PRP formulations to optimize efficacy while minimizing variability.

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