Targeting neutrophil extracellular trap accumulation under flow in patients with immune-mediated thrombotic thrombocytopenic purpura

• DOI: 10.1182/bloodadvances.2023011617
• Publication Date: 2024-03-21T18:48:14Z
• Authors: Noritaka Yada; Quan Zhang; Antonia Bignotti; Sarah H. Gralnek; Dennis Sosnovske; Keenan Hogan; Zhan Ye; Liang Zheng; X. Long Zheng
• Keywords: Neutrophil Extracellular Traps; Trap (plumbing)

Neutrophil NETosis is a unique form of cell death, characterized by the release decondensed chromatin and antimicrobial contents to extracellular space, which involved in inflammation thrombosis. However, role pathogenesis immune-mediated thrombotic thrombocytopenic purpura (iTTP) how targeted therapy affects accumulation neutrophil traps (NETs) under flow remain unknown. Flow cytometry demonstrated that percentage neutrophils undergoing whole blood from patients with iTTP on admission was significantly increased, concurrent decrease capacity inducible shigatoxin. After therapy, H3Cit+MPO+ reduced, an improvement these patients. Additionally, little no NET thrombus formation detected underflow when platelet counts were very low, but dramatically increased following rose ≥50 × 109/L or restored normal donor platelets. Similarly, there vwf-/- mice, higher Adamts13-/- mice than wild-type mice. Finally, recombinant ADAMTS13 caplacizumab (or anfibatide) prevented These results indicate depend platelets von Willebrand factor (VWF) iTTP, such as may prevent iTTP.