Defibrotide is a heterogenous mixture of polyanionic oligonucleotides currently approved for treatment of transplant-associated veno-occlusive disease. While defibrotide has a known role in limiting endothelial cell activation, some studies have also demonstrated anti-leukocyte properties. We recently revealed a role for neutrophil extracellular traps (NETs) in the thrombotic complications of antiphospholipid syndrome (APS). Here, we hypothesized that defibrotide might act to mitigate APS-relevant NET formation in vitro and in mouse models.
We used in vitro assays and a mouse model to determine mechanisms by which defibrotide inhibits NET formation and venous thrombosis in APS.
At doses ranging from 1 to 10 μg ml
This study is the first to demonstrate mechanisms by which defibrotide counteracts neutrophil-mediated thrombo-inflammation inherent to APS.