Thrombosis – the formation of a blood clot within arteries or veins – is the main reason for blood vessel occlusion, leading to myocardial infarction, stroke, and pulmonary embolism. The process of blood clot formation is driven by the aggregation of blood platelets and the formation of fibrin strands. Conventional antithrombotic drugs target these events to disintegrate blood clots. Recent evidence indicates that neutrophils participate in blood clot formation through the release of DNA filaments that form web-like structures known as neutrophil extracellular traps (NETs). To achieve this, neutrophils disassemble their nucleus and unfold DNA into loose strands, serving as a stimulus and scaffold for platelet binding and fibrin activation. As a consequence, NETs accelerate thrombosis and blood clots are more stable in the presence of NETs. NETs are also associated with thrombosis in patients and may thus serve as a new therapeutic target. Scientists on the EU-funded NET-LYSIS (Degradation of neutrophil extracellular traps and its impact on thrombolysis) project set out to investigate whether efficient thrombolysis would require NET degradation. For this purpose, they analysed acute thrombotic microangiopathies (TMAs), a heterogeneous group of life-threatening conditions characterised by disseminated microvascular thrombosis. Since markers of NETs have been identified in TMAs, the consortium hypothesised that their timely and efficient removal would prevent excessive thrombosis. Scientists observed that TMA patient plasma was unable to degrade NETs in vitro, concomitant with a reduced DNase activity. Supplementation of TMA plasma with recombinant human DNase1 restored NET-degradation activity, indicating that DNase1-mediated degradation of NETs is impaired in patients with TMAs. Taken together, the results of the NET-LYSIS study underscored the role of NETs in thrombosis and suggested that plasma DNases could serve as new drug candidates for thrombolytic therapy in the future.
Neutrophil, blood clot, thrombosis, DNA filaments, neutrophil extracellular traps, acute thrombotic microangiopathies, DNase