Search

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 (K s ), 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 K s 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., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background:  Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics., Methods:  We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48-70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability ( K s ), clot lysis time (CLT), thrombin generation, platelet-derived markers, and fibrinolytic parameters were measured on admission. Plasma fibrin clot morphology was assessed by scanning electron microscopy (SEM)., Results:  Patients with central PE ( n  = 76; 60.3%) compared with peripheral PE ( n  = 50; 39.7%) had 17.8% higher K s and 14.3% shortened CLT (both p  < 0.01 after adjustment for potential confounders including fibrinogen), with no differences between segmental and subsegmental PE. SEM analysis demonstrated larger fibrin fiber diameter and pore size in central PE compared with peripheral PE (both p  < 0.01). For isolated PE, there was 23.3% higher K s in central PE than in peripheral PE ( n  = 24; 19%) with no differences in other variables. Central PE combined with DVT ( n  = 45; 35.7%), as compared with central isolated PE ( n  = 31; 24.6%), was associated with shortened CLT (all p  < 0.05)., Conclusion:  Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability., Competing Interests: None declared., (Thieme. All rights reserved.)

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.

Background: Underuse of thromboprophylaxis in hospitalized medical patients is still common worldwide. Little is known about the use of thromboprophylaxis in patients with pulmonary diseases in everyday hospital practice., Objectives: The aim of this study was to assess the use of pharmacological prophylaxis of venous thromboembolism (VTE) in real-life patients with pulmonary diseases., Material and Methods: In this retrospective study, 2 validated scoring systems, i.e., the Padua prediction score and Caprini VTE risk assessment, were used to assess the VTE risk in 2011 patients (1133 men and 878 women), aged 18 years or more, hospitalized for pulmonary diseases (median 6 days) in a single tertiary pulmonary medical center from January to December 2014., Results: Using the Padua prediction score, we identified 428 (21.28%) patients at a high risk for VTE, including 167 (39.01%) who received thromboprophylaxis with low-molecular-weight heparin, and 261 (60.98%) individuals at a high risk without thromboprophylaxis (p < 0.001). A total of 888 (44.16%) patients who scored 5 points or more using the Caprini VTE risk assessment were identified as subjects at a high risk for VTE, including 34.79% of patients receiving thromboprophylaxis. From among patients at a high risk for VTE, 579 (65.20%) did not receive appropriate thromboprophylaxis (p < 0.001). Underuse of thromboprophylaxis was observed more commonly among patients hospitalized for lung cancer or pneumonia (50.60% and 24.87% of patients at a high risk for VTE without prophylaxis, respectively)., Conclusions: Thromboprophylaxis is underutilized in hospitalized patients with pulmonary diseases regardless of the scoring system used. Implementation of thromboprophylaxis should be markedly improved in this patient group.

Objective: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism with a high recurrence rate after anticoagulation cessation. Recently, we have reported that prothrombotic clot phenotype in venous thromboembolism patients is associated with an increased risk of recurrent deep-vein thrombosis., Approach and Results: We tested whether abnormal clot properties are predictive of recurrent PE. We investigated 156 consecutive white patients aged 18 to 65 years after the first-ever provoked or unprovoked PE (n=89), with or without deep-vein thrombosis. Plasma fibrin clot permeability (K s ), turbidity measurements, calibrated automated thrombography, and efficiency of fibrinolysis using clot lysis time, maximum D-dimer levels, and rate of increase in D-dimer levels were evaluated at ≥3 months of anticoagulant therapy, at least 4 weeks since the anticoagulation withdrawal. The primary end point was recurrent PE during a median follow-up of 50 months. Recurrent PE was diagnosed in 23 (14.7%; 5%/yr) patients. Recurrent PE was associated with formation of denser fibrin networks reflected by lower K s (P=0.007) and impaired fibrinolysis, as evidenced by prolonged clot lysis time (P=0.012) and reduced maximum rate of increase in D-dimer levels in the lysis assay (P=0.004). Patients with recurrent PE had higher plasma D-dimer (P<0.001) and thrombin peak (P=0.007) compared with the remainder, whereas turbidity measurements and maximum D-dimer levels did not differ in the recurrence. Multivariate model showed that independent predictors of recurrent PE were female sex, unprovoked venous thromboembolism, higher plasma D-dimer, reduced K s , and reduced maximum rate of increase in D-dimer levels in the lysis assay (all P<0.05)., Conclusions: Altered fibrin clot properties including formation of more compact clots displaying impaired susceptibility to lysis may predispose to recurrent PE., (© 2016 American Heart Association, Inc.)