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

• Published in: European journal of clinical investigation Vol. 52; no. 1; pp. e13660 - n/a
• Main Authors: Ząbczyk, Michał, Natorska, Joanna, Janion‐Sadowska, Agnieszka, Metzgier‐Gumiela, Agnieszka, Polak, Mateusz, Plens, Krzysztof, Janion, Marianna, Skonieczny, Grzegorz, Mizia‐Stec, Katarzyna, Undas, Anetta
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2022
• Subjects: 8‐isoprostane; Adult; Aged; Anticoagulants; Biomarkers; Biomarkers - blood; Brain natriuretic peptide; Confidence intervals; Differentiation; Dinoprost - analogs & derivatives; Dinoprost - blood; Embolism; Female; Fibrin; fibrin clot; Fibrinolysis; growth differentiation factor 15; Growth Differentiation Factor 15 - blood; Humans; Inhibitors; Lysis; Male; Middle Aged; Oxidative Stress; Pathogenesis; Permeability; Plasminogen activator inhibitors; post‐PE syndrome; pulmonary embolism; Pulmonary Embolism - blood; Pulmonary Embolism - complications; Pulmonary Embolism - metabolism; Pulmonary embolisms; Syndrome; Thrombin; Thrombosis - complications; Thrombosis - metabolism; fibrin clot; 8-isoprostane; post-PE syndrome; pulmonary embolism; growth differentiation factor 15; oxidative stress
• ISSN: 0014-2972; 1365-2362; 1365-2362
• DOI: 10.1111/eci.13660

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.