Venous thromboembolism is associated with formation of denser fibrin clots resistant to lysis. We investigated whether prothrombotic plasma clot properties are associated with the severity of acute pulmonary embolism (PE). We enrolled 126 normotensive acute PE patients (aged 58 ± 14 years) and 25 age- and sex-matched healthy controls. Plasma fibrin clot permeability (K_s), clot lysis time (CLT), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), and citrullinated histone H3 (citH3) were evaluated on admission. PE patients compared to controls had 370% higher citH3 levels, 41% higher ETP, 16.5% reduced K_s, and 25.6% prolonged CLT. Patients with intermediate-high (n = 29) and intermediate-low (n = 77) PE mortality risk had reduced K_s and prolonged CLT, increased PAI-1 and ETP as compared to low-risk PE (n = 20) patients. Prolonged CLT was predicted by PAI-1 and citH3, while low K_s by C-reactive protein. During a 12-month follow-up 9 (7.1%) patients who had 24% higher ETP, 45% higher citH3 levels, and 18% prolonged CLT at baseline died. High ETP combined with elevated citH3 levels and prolonged CLT was associated with eightfold increased risk of PE-related death. Prothrombotic fibrin clot properties and enhanced neutrophil extracellular traps formation are associated with higher early mortality risk in acute PE patients, which suggests a prognostic role of these biomarkers.

静脉血栓栓塞症与抗裂解的致密纤维蛋白凝块形成有关。我们调查了血栓前血浆凝块特性是否与急性肺栓塞（PE）的严重程度有关。我们招募了126名血压正常的急性PE患者（年龄58±14岁）和25名年龄和性别相匹配的健康对照。入院时评估血浆纤维蛋白凝块通透性（K _s），凝块溶解时间（CLT），内源性凝血酶电势（ETP），纤溶酶原激活物抑制剂1（PAI-1）和瓜氨酸化组蛋白H3（citH3）。与对照组相比，PE患者的citH3水平高370％，ETP高41％，K _s降低16.5％，CLT延长25.6％。中高（n = 29）和中低（n = 77）PE死亡风险的患者的K _s降低与低危PE（n = 20）患者相比，CLT延长，PAI-1和ETP升高。PAI-1和citH3预测CLT延长，而C反应蛋白降低K _s。在12个月的随访期间，有9名（7.1％）的患者在基线时ETP高24％，citH3水平高45％和CLT延长18％的患者死亡。高ETP加上citH3水平升高和CLT延长与PE相关死亡风险增加了八倍。血栓前纤维蛋白凝块特性和嗜中性粒细胞胞外陷阱形成的增强与急性PE患者早期死亡风险较高有关，这提示这些生物标志物的预后作用。