Assessment of adverse events and safety associated with intra‐articular platelet‐rich plasma injections compared to other injectates for knee osteoarthritis: A systematic review and meta‐analysis

OBJECTIVE: To evaluate adverse events (AEs) associated with intra-articular platelet-rich plasma (IA-PRP) injections for knee osteoarthritis (KOA) and compare their rates with those of intra-articular corticosteroids (IA-CS), hyaluronic acid (IA-HA), and normal saline (IA-NS). LITERATURE SURVEY: A systematic search of PubMed, Embase, and Cochrane Library databases identified randomized controlled trials (RCTs) published after 2015. Studies were included if they reported AEs related to IA-PRP injections for KOA and provided comparator data for IA-CS, IA-HA, or IA-NS. METHODOLOGY: Data on AEs were extracted and categorized into mild knee pain and swelling, severe knee pain requiring withdrawal, knee stiffness, other musculoskeletal (MSK) events, non-MSK events, and severe AEs. A random-effects meta-analysis was performed to calculate odds ratios (OR) with 95% confidence intervals (CI) for AE rates in IA-PRP versus comparator groups. Subgroup analysis was conducted to evaluate the effects of leukocyte concentration on AE rates. SYNTHESIS: Thirty-two RCTs published articles, involving 1268 IA-PRP-treated knees, met inclusion criteria. AEs were reported in 18.7% of IA-PRP cases, with mild knee pain and swelling being the most common (10.6%). Compared to IA-HA, IA-PRP had significantly higher rates of mild knee pain and swelling (p < .001). Subgroup analysis revealed that this difference was significant only for leukocyte-rich IA-PRP (p < .05), whereas leukocyte-poor IA-PRP showed no significant difference compared to IA-HA (p = .51). Knee stiffness was more frequent in IA-PRP versus IA-NS (p = .031). There were no significant differences in other AE categories, and no severe AEs were reported across any groups. CONCLUSIONS: IA-PRP injections are associated with mild, transient AEs such as knee pain and swelling, particularly with leukocyte-rich PRP formulations. These symptoms typically resolve without intervention. Leukocyte-poor IA-PRP showed a similar safety profile to IA-HA. No severe AEs were observed, supporting the overall safety of IA-PRP for KOA. Clinicians should counsel patients on the likelihood of mild postprocedure symptoms, especially with high leukocyte formulations, while considering IA-PRP as a treatment option.