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

Haemophilia. 2022 Mar;28(2):351-361. doi: 10.1111/hae.14508. Epub 2022 Feb 13.

Abstract

Introduction: Hemarthrosis causes chronic haemophilic synovitis (CHS). Although neutrophils are major immune 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 that were associated with tissue damage.

Aims: To evaluate the presence of ETs as pathogenic biomarker and the protective effect of intraarticular injection of platelet-rich plasma (PRP) in patients with CHS.

Methods: Haemophilia Joint Health Score (HJHS) and bleeding episodes (BE) were measured and correlated with ETs indicators (DNA/DNA-Elastase) in synovial fluids (SF), PRP and plasma of 21 patients.

Results: Soluble DNA and DNA-Elastase were detected in SF and plasma of patients. The synovial and plasma levels of DNA-Elastase positively correlated with worse HJHS/BE. Interestingly, remaining ETs-inducer factors were present in SF that induced the in vitro release of ETs from blood-isolated neutrophils. This phenomenon was impaired by adding plasma or PRP. Finally, preliminary data obtained from five patients indicate that levels of DNA-Elastase and HJHS/BE decreased after receiving intraarticular injection of PRP.

Conclusions: The synovial and plasma levels of DNA-Elastase correlated with worse HJHS/BE 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. However, our hypotheses must be confirmed in the future with better designed and more statistical power studies. Meanwhile, the use of intraarticular injections of PRP for the treatment of CHS remains controversial.

Keywords: DNA extracellular traps; chronic haemophilic synovitis; haemophilia; platelet-rich plasma.

MeSH terms

  • Biomarkers
  • DNA / metabolism
  • Extracellular Traps*
  • Hemophilia A* / drug therapy
  • Humans
  • Injections, Intra-Articular
  • Pilot Projects
  • Platelet-Rich Plasma* / metabolism
  • Synovitis* / drug therapy
  • Synovitis* / therapy

Substances

  • Biomarkers
  • DNA