Isoprostane‐8 and GDF‐15 as novel markers of post‐PE syndrome: Relation with prothrombotic factors.

Background: Post–pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. Objective: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post‐PE syndrome. Methods: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5‐7 days and after a 3‐month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8‐isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks), along with PE biomarkers, were determined. Results: Patients who developed the post‐PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N‐terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor‐1 as compared to subjects without post‐PE syndrome (all P <.05). After 5‐7 days, only hypofibrinolysis was noted in post‐PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post‐PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor‐1 (all P <.05). 8‐isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63‐12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29‐12.16) measured at 3 months were associated with higher risk of developing post‐PE syndrome. Conclusions: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post‐PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome. [ABSTRACT FROM AUTHOR]