Leukocyte-rich versus leukocyte-poor platelet-rich plasma and hyaluronic acid for knee osteoarthritis: a systematic review and network meta-analysis

Objective: To compare the comparative efficacy and safety of leukocyte-rich platelet-rich plasma (L-PRP), leukocyte-poor platelet-rich plasma (LP-PRP), hyaluronic acid (HA), and placebo for the treatment of knee osteoarthritis (KOA). Design: Systematic review and network meta-analysis of randomized controlled trials (RCTs). Data sources: A comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was conducted from inception to October 2025, without language restrictions. Eligibility criteria for selecting studies: We included RCTs that compared at least two of the following interventions in patients with KOA: L-PRP, LP-PRP, HA, or placebo. The primary outcome was functional improvement measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were pain reduction and the incidence of short-term adverse events. Results: Twenty-one RCTs, comprising 2,254 patients, were included. The network meta-analysis demonstrated that for functional improvement at 6–12 months, both L-PRP (Mean Difference [MD] vs. placebo: −13.20; 95% Confidence Interval [CI]: −20.80 to -5.60) and LP-PRP (MD: −10.54; 95% CI: −18.37 to -2.71) were significantly superior to placebo. Both were also superior to HA. According to P-score rankings, LP-PRP was the most effective treatment for function (0.96), followed by L-PRP (0.82). However, the direct comparison between LP-PRP and L-PRP showed no statistically significant difference in efficacy. For pain reduction, all active treatments were superior to placebo. While L-PRP was associated with a higher incidence of transient local adverse events, the data were inconsistently reported. Sensitivity analyses confined to studies with a low risk of bias confirmed the robustness of these findings. Conclusion: Intra-articular PRP provides clinically significant functional improvement and pain relief for patients with KOA, with an efficacy superior to that of HA. Both L-PRP and LP-PRP are effective treatment options with comparable efficacy based on current evidence. Although qualitative trends suggest a potentially better safety profile for LP-PRP, robust data are lacking. Therefore, there is insufficient evidence to recommend one PRP formulation over the other. Supplementary Information: The online version contains supplementary material available at 10.1186/s13018-026-06689-4.