DNA extracellular traps as potential biomarker of chronic haemophilic synovitis and therapeutic perspective in patients treated with PRP

ONETO, P; LANDRO, ME; DAFFUNCHIO, C; DOUGLAS PRICE, AL; CARRERA SILVA, EA; CAVIGLIA, H; ETULAIN, J

Londres

Congreso; XXX Congress of the International Society on Thrombosis and Haemostasis; 2022

International Society on Thrombosis and Haemostasis

Background: Haemophilia-associated hemarthrosis cause chronic haemophilic synovitis (CHS). Although neutrophils are major immune blood cells infiltrating joints after bleeding, their role on the pathogenesis of CHS is unknown. Neutrophils release extracellular DNA traps (ETs), structures of DNA with bound granular enzymes (including elastase) that were associated with tissue damage. Aims: To evaluate the presence of ETs as pathogenic biomarkers, and the protective effect of intraarticular injection of platelet-rich plasma (PRP) in patients with CHS.Methods: Synovial fluids (SF) and plasma/PRP were obtained from 21 patients with CHS (28±11 years old, 19 type A, 2 type B). 22 joints (1 ankle and 21 knees) were evaluated for Hemophilia Joint Health Score (HJHS). Synovial and plasmatic ETs were indirectly quantified by fluorometry (DNA) and directly by ELISA (DNA-Elastase complexes). Pearson or Spearman correlations with clinical parameters were calculated. Results: DNA (0.37±0.06μg/ml) and DNA-Elastase (0.27±0.03OD) were detected in SF of patients with CHS and positively correlated with HJHS (r>0.5-0.7, p0.05) with the synovial levels of both parameters. Remaining ETs-inducer factors were present in SF, as this fluid induced the in vitro release of ETs from blood-isolated neutrophils. This phenomenon was impaired by adding plasma or PRP. Finally, promising preliminary data with 5 patients with CHS indicate that levels of DNA-Elastase and joint damage decreased after 2 weeks of receiving intra-articular injection of PRP.Conclusions: The synovial and plasma levels of DNA-Elastase correlated with joint damage suggesting that ETs formation could be a biomarker and potential therapeutic target for CHS. The intraarticular injection of PRP underlined a new potential alternative therapy, decreasing ETs formation in synovia of patients with CHS.