NETs contribute to acute episodes but not ADAMTS13 relapses in immune-mediated thrombotic thrombocytopenic purpura.
Publisher DOI
PubMed ID
42339313
Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) results from acquired severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13). Neutrophil extracellular traps (NETs) contribute to acute iTTP episodes, but their role across different clinical stages and treatment modalities remains unclear. We conducted a retrospective, observational study in 8 patients with iTTP followed up for 7.4 years (range, 0.4-15.2). Patients experienced 8 first acute episodes (3 caplacizumab treated), 14 ADAMTS13 relapses, and 6 clinical relapses (2 caplacizumab treated), interjected by remissions. Besides clinical and ADAMTS13 parameters, we measured NET markers, including circulating DNA, myeloperoxidase (MPO), neutrophil elastase, and citrullinated histone H3. All NET markers were elevated at presentation with acute iTTP episodes and rapidly declined during treatment. The magnitude of NET marker reduction 3 days after treatment initiation was similar with and without caplacizumab (DNA, -61% ± 21% vs -49% ± 23%; MPO, -15% ± 49% vs -46% ± 33%). In the second week, patients treated without caplacizumab presented with another NET marker surge, paralleled by a drop in platelet counts; both were absent in caplacizumab-treated patients. NET levels remained unchanged during ADAMTS13 relapses compared to remission (DNA, 1.1-fold; MPO, 1.1-fold), whereas increases were documented in overt clinical relapses (DNA, 4.3-fold; MPO, 3.2-fold). Our findings indicate NET involvement in acute iTTP pathophysiology but suggest that NET formation requires a secondary trigger beyond ADAMTS13 deficiency. The second wave of NET formation and renewed platelet decline may be driven by von Willebrand factor-platelet interactions, as the phenomenon is absent in caplacizumab-treated patients. Our data support the benefit of preemptive immunosuppressive treatment for ADAMTS13 relapses.
Date Issued
2026-08
Publication Type
Article
Language(s)
en
Author(s)
Journal
Blood: Vessels, Thrombosis & Hemostasis
Publisher
American Society of Hematology (ASH Publications)
ISSN
2950-3272
Access(Rights)
open.access