Microclot and NET Structural Interventions
(Certainty: 0.25.) Thierry et al. (Thierry et al. 2025) demonstrated that NETs are structurally incorporated into microclots in long COVID, with NET markers (MPO, NE, cfDNA) colocalising with microclot cores. This suggests NET scaffolding stabilizes microclots—a mechanism that would make microclots resistant to standard anticoagulants (heparin, DOACs) that target fibrin but not extracellular DNA. DNase I, by degrading the NET scaffold, could destabilize microclots without anticoagulant-associated bleeding risk—an attractive safety profile for ME/CFS patients with concurrent dysautonomia and fall risk. However, clinical microclot effects are unproven in ME/CFS, and the functional significance of microclots for symptoms is debated.
Key prediction: In vitro incubation of ME/CFS microclots with DNase I should reduce clot size and structural integrity. Falsified if microclots are DNase-resistant (suggesting fibrin-dominant composition without NET scaffolding).
Limitation: Microclot measurement is non-standardized; clinical significance unknown; no ME/CFS microclot-NET colocalisation data exist.