Abstract
Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have a two- to threefold greater risk of developing venous as well as arterial thrombotic events. Although such thrombotic events are more commonly seen during phases of active AAV, they are also recognized to occur during AAV in remission. Endothelial injury is a key pathogenic event in AAV. Endothelial injury can be caused by neutrophil activation and release of thrombogenic tissue factor into the circulation. Neutrophil activation further results in the formation of neutrophil extracellular traps (NETs). NETs contribute to thrombosis by expressing tissue factor. NETs have also been detected in cutaneous thrombi from patients with AAV induced by hydralazine. Activated neutrophils in AAV patients release thrombogenic microparticles loaded with tissue factor which further enhances clotting of blood. Antiphospholipid antibodies (APLs) have been detected in up to a third of AAV and might also be induced by drugs such as cocaine adulterated with levamisole and propylthiouracil, which are known to trigger AAV. Such APLs further drive the thrombosis in AAV. Once thrombogenesis occurs, the homeostatic mechanisms resulting in clot dissolution are further impaired in AAV due to anti-plasminogen antibodies. The ongoing pandemic of coronavirus disease 2019 (COVID-19) is associated with endothelial injury and NETosis, mechanisms which are in common with AAV. Reports of new-onset AAV following COVID-19 have been described in the literature, and there could be shared mechanisms driving these processes that require further evaluation.
Keywords: Anti-neutrophil cytoplasmic antibody-associated vasculitis; Antiphospholipid antibodies; Deep vein thrombosis; Embolism and thrombosis; Neutrophil extracellular traps; Vascular endothelium.
【저자키워드】 Neutrophil extracellular traps, antiphospholipid antibodies, Anti-neutrophil cytoplasmic antibody-associated vasculitis, Deep vein thrombosis, Embolism and thrombosis, Vascular endothelium., 【초록키워드】 COVID-19, coronavirus disease, Neutrophils, antibodies, Coronavirus disease 2019, pandemic, thrombosis, antibody, Neutrophil extracellular traps, neutrophil, risk, drug, cocaine, Endothelium, Patient, clotting, Neutrophil extracellular trap, NETosis, Vasculitis, endothelial injury, circulation, Thrombotic events, NETs, mechanism, antiphospholipid antibodies, Blood, Deep vein thrombosis, Embolism and thrombosis, Levamisole, Embolism, Activated neutrophils, Tissue Factor, Injury, Trigger, neutrophil activation, Deep vein, antiphospholipid antibody, anti-neutrophil cytoplasmic antibody, Remission, Vascular endothelium, Activation, Propylthiouracil, hydralazine, tissue, thrombotic, pathogenic, report, driving, thrombi, thrombogenesis, Microparticle, NET, venous, thrombotic event, Extracellular, ENhance, greater, resulting, described, caused, contribute, occur, cytoplasmic, expressing, APL, homeostatic,