Non-anticoagulant heparin attenuates histone-mediated platelet–leukocyte aggregation and neutrophil extracellular trap formation in a canine whole blood model

Introduction: canine model of septic and aseptic inflammation. We hypothesized that NACH would be non-inferior to UFH in attenuating histone-mediated NET formation and platelet-leukocyte, platelet-neutrophil aggregate formations. Methods: ) to simulate SIRS and sepsis, respectively. Samples were then treated with increasing concentrations of UFH (0, 0.4, 4 and 40 U/mL) or NACH (0, 1, 5, 10 μg/mL). Platelet-leukocyte and neutrophil-platelet aggregates were identified via flow cytometry using fluorophore-conjugated antibodies against platelets (CD61), leukocytes (CD18), and canine neutrophils. NET formation was assessed by quantifying cell-free DNA and intracellular citrullinated histones H3 (citH3) by flow cytometry. Results: model, but only high-dose NACH was able to module neutrophil extracellular trap formation in the histone mediated model. Conclusion: -mediated responses. Both forms of heparin modulate NETs formation, highlighting their distinct stimulus-specific anti-inflammatory effects.