FXII – between hypercoagulation and fibrinolysis shutdown in COVID-19 (A02)

FXII â COVID-19 中高凝与纤溶关闭之间的关系 (A02)

• 批准号: 178198475
• 金额: --
• 依托单位: Biochemisches Institut
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/178198475?language=en
• 关键词: FXII; between; hypercoagulation; fibrinolysis; shutdown

The high incidence of thrombotic events, in conjunction with prolonged activated partial thromboplastin time, suggests a possible role of coagulation factor XII (FXII) in COVID-19 pathology. FXII is a serine protease that circulates in plasma as a zymogen. Following contact with damage-associated molecular patterns such as neutrophil extracellular traps, extracellular RNAs, and polyphosphates, FXII undergoes autoactivation to FXIIa. FXIIa controls thrombus formation while being dispensable for hemostasis. Given uncontrolled neutrophil activation and widespread endothelial damage in severe COVID-19, we postulate that augmented FXIIa formation causes COVID-19-associated hypercoagulability by altering clot structure and impairing fibrinolysis. To address this objective, FXII tracing in severe COVID-19 plasma and clot formation and lysis assays, in conjunction with ex vivo and in situ clot imaging, will be performed. The results of our work are expected to recognize FXII as a propagator of thrombotic events in severe COVID-19 patients and open new treatment perspectives.

血栓事件的高发生率，加上活化的部分凝血活酶时间的延长，提示凝血因子XII在新冠肺炎的病理过程中可能起到了作用。FXII是一种丝氨酸蛋白酶，以酶原的形式在血浆中循环。在与中性粒细胞胞外陷阱、胞外RNA和多聚磷酸盐等损伤相关分子模式接触后，FXII经历了对FXIIa的自动激活。FXIIa在控制血栓形成的同时，对于止血也是必不可少的。考虑到严重新冠肺炎患者中性粒细胞激活失控和广泛的内皮损伤，我们推测FXIIa的形成增加通过改变凝块结构和损害纤溶作用而导致新冠肺炎相关的高凝状态。为了实现这一目标，将结合体外和原位血栓成像，对严重的新冠肺炎血浆和凝块形成和溶解分析进行FXII示踪。我们的工作结果有望确认FXII是重症新冠肺炎患者血栓事件的传播者，并开辟新的治疗视角。