Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system’s cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.

Chronic hemophilic synovitis (CHS), driven by hemosiderin-laden macrophages from recurrent hemarthrosis, is a major cause of joint damage in hemophilia. Platelet-rich plasma (PRP) is a promising regenerative therapy for joint diseases. This study investigated PRP’s ability to modulate macrophage polarization from a pro-inflammatory (M1) to a pro-resolving, tissue-repairing (M2) phenotype in CHS. We analyzed synovial fluid (SF) from CHS patients (N = 22), both pre- and post-PRP treatment. Ex vivo analysis revealed a predominant M1 profile with an increased proportion of CD11⁺CD14⁺CD64^hi compared with CD206⁺ or CD163⁺ M2 macrophages in CHS SF. In vitro experiments showed that CHS SF skewed monocyte-derived macrophages toward an M1 inflammatory program, evaluated by flow cytometry, qPCR, and ELISA. However, adding PRP significantly modulated the pro-inflammatory macrophage program, promoting an M2 tissue repair profile. Furthermore, a random forest machine learning algorithm, applied to public scRNAseq data, confirmed PRP’s macrophage reprogramming effect. Functional assays also showed increased TGF-β secretion and macrophage fusion when challenged with neutrophil extracellular traps (NETs). A small patient follow-up cohort treated with intra-articular PRP showed similar results, including normalization of cellular content and reduced CD64/CD206 expression. These findings indicate that PRP treatment effectively shifts SF-associated M1 macrophages to an M2-like phenotype, highlighting its potential as a therapeutic strategy for CHS.