PMID- 32651425 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210710 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Jul 10 TI - Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk. PG - 11433 LID - 10.1038/s41598-020-68375-7 [doi] LID - 11433 AB - 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. FAU - Zabczyk, Michal AU - Zabczyk M AD - Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St.,, 31-202, Krakow, Poland. AD - John Paul II Hospital, Krakow, Poland. FAU - Natorska, Joanna AU - Natorska J AD - Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St.,, 31-202, Krakow, Poland. AD - John Paul II Hospital, Krakow, Poland. FAU - Janion-Sadowska, Agnieszka AU - Janion-Sadowska A AD - The Faculty of Medicine and Health Sciences, The Jan Kochanowski University, Kielce, Poland. FAU - Metzgier-Gumiela, Agnieszka AU - Metzgier-Gumiela A AD - Provincial Polyclinical Hospital, Torun, Poland. FAU - Polak, Mateusz AU - Polak M AD - First Department of Cardiology, Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University, Katowice, Poland. FAU - Plens, Krzysztof AU - Plens K AD - KCRI, Krakow, Poland. FAU - Janion, Marianna AU - Janion M AD - The Faculty of Medicine and Health Sciences, The Jan Kochanowski University, Kielce, Poland. FAU - Skonieczny, Grzegorz AU - Skonieczny G AD - Provincial Polyclinical Hospital, Torun, Poland. FAU - Mizia-Stec, Katarzyna AU - Mizia-Stec K AD - First Department of Cardiology, Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University, Katowice, Poland. FAU - Undas, Anetta AU - Undas A AD - Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St.,, 31-202, Krakow, Poland. mmundas@cyf-kr.edu.pl. AD - John Paul II Hospital, Krakow, Poland. mmundas@cyf-kr.edu.pl. AD - The Faculty of Medicine and Health Sciences, The Jan Kochanowski University, Kielce, Poland. mmundas@cyf-kr.edu.pl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200710 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Histones) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (SERPINE1 protein, human) RN - 9001-31-4 (Fibrin) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Adult MH - Aged MH - Biomarkers MH - Blood Coagulation Tests MH - Case-Control Studies MH - *Extracellular Traps MH - Female MH - Fibrin/chemistry MH - Fibrin Clot Lysis Time MH - Fibrinolysis MH - Follow-Up Studies MH - Histones/blood MH - Humans MH - Male MH - Middle Aged MH - Plasminogen Activator Inhibitor 1/blood MH - Prognosis MH - Pulmonary Embolism/*blood/mortality MH - Risk MH - Sensitivity and Specificity MH - Thrombin/metabolism MH - Thrombosis/*blood MH - Venous Thromboembolism/blood/mortality PMC - PMC7351737 COIS- The authors declare no competing interests. EDAT- 2020/07/12 06:00 MHDA- 2021/01/12 06:00 PMCR- 2020/07/10 CRDT- 2020/07/12 06:00 PHST- 2019/10/29 00:00 [received] PHST- 2020/02/12 00:00 [accepted] PHST- 2020/07/12 06:00 [entrez] PHST- 2020/07/12 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] PHST- 2020/07/10 00:00 [pmc-release] AID - 10.1038/s41598-020-68375-7 [pii] AID - 68375 [pii] AID - 10.1038/s41598-020-68375-7 [doi] PST - epublish SO - Sci Rep. 2020 Jul 10;10(1):11433. doi: 10.1038/s41598-020-68375-7.