Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Semin Thromb Hemost. 2017 Sep;43(6):553-561. doi: 10.1055/s-0036-1597284. Epub 2017 Mar 30.
Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism. ceDNA correlates with markers of coagulation and platelet consumption, thus supporting the hypothesis that ceDNA may be a surrogate marker of thrombus formation. In addition, ceDNA levels correlate with markers of cell injury and size of ischemic lesions, suggesting that ceDNA does not derive from NETs but is probably released from damaged organs. Few studies identified NET-specific biomarkers such as DNA-MPO complexes in the blood of patients with thrombosis. In conclusion, it remains to be established whether ceDNA in patients derives from NETs and is a cause or consequence of thrombosis.
血栓形成导致心血管和血栓栓塞疾病中的缺血性器官损伤。中性粒细胞通过释放中性粒细胞胞外诱捕网（NETs）在体外和体内促进血栓形成。NETs 由 DNA 丝组成，表面覆盖组蛋白和中性粒细胞酶，如髓过氧化物酶（MPO）。循环细胞外 DNA（ceDNA）被广泛用作监测血栓形成中 NET 形成的替代标志物。本综述总结了 ceDNA 与人类血栓形成的关系。ceDNA 水平表明包括心肌梗死、中风和静脉血栓栓塞在内的几种心血管和血栓栓塞疾病的严重程度和结局。ceDNA 与凝血和血小板消耗的标志物相关，因此支持 ceDNA 可能是血栓形成的替代标志物的假说。此外，ceDNA 水平与细胞损伤和缺血性损伤的大小的标志物相关，表明 ceDNA 不是来自 NETs，而是可能来自受损器官。少数研究在血栓形成患者的血液中鉴定出 NET 特异性生物标志物，如 DNA-MPO 复合物。总之，尚需确定患者中的 ceDNA 是否来自 NETs，以及是否是血栓形成的原因或后果。
