Fibrinogen β chain and FXIII polymorphisms affect fibrin clot properties in acute pulmonary embolism

Author(s):  
Adrianna Klajmon ◽  
Jakub Chmiel ◽  
Michał Ząbczyk ◽  
Elżbieta Pociask ◽  
Ewa Wypasek ◽  
...  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Agnieszka Janion-Sadowska ◽  
Agnieszka Metzgier-Gumiela ◽  
Mateusz Polak ◽  
...  

Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Agnieszka Janion-Sadowska ◽  
Agnieszka Metzgier-Gumiela ◽  
Mateusz Polak ◽  
...  

Abstract 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.


2020 ◽  
Vol 229 ◽  
pp. 103946
Author(s):  
Agata Hanna Bryk ◽  
Joanna Natorska ◽  
Michał Ząbczyk ◽  
Katharina Zettl ◽  
Jacek R. Wiśniewski ◽  
...  

2020 ◽  
Vol 133-134 ◽  
pp. 106783
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Krzysztof P. Malinowski ◽  
Anetta Undas

2020 ◽  
Vol 9 (4) ◽  
pp. 953 ◽  
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Agnieszka Janion-Sadowska ◽  
Krzysztof P. Malinowski ◽  
Marianna Janion ◽  
...  

Background: Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE. Methods: As many as 126 normotensive acute PE patients (aged 58 ± 14 years) were enrolled. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), citrullinated histone H3 (citH3), and plasminogen activator inhibitor-1 antigen (PAI-1), together with plasma L-lactate levels were evaluated on admission. Results: Lactate levels ≥2 mM were found in 70 (55.6%) patients in whom we observed 29% higher neutrophil count and 45% elevated plasma citH3 levels. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced Ks, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 min was shown in the linear regression. Conclusions: Our findings suggest a new mechanism contributing to a negative impact of elevated lactate levels on prognosis in acute PE patients, in particular hypofibrinolysis, associated with enhanced NET formation.


VASA ◽  
2014 ◽  
Vol 43 (6) ◽  
pp. 450-458 ◽  
Author(s):  
Julio Flores ◽  
Ángel García-Avello ◽  
Esther Alonso ◽  
Antonio Ruíz ◽  
Olga Navarrete ◽  
...  

Background: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). Patients and methods: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. Results: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88–100 %)/95 % (95 % CI, 88–100 %) and 95 % (95 % CI, 88–100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21–37 %) for D-dimer and 24.4 % (95 % CI, 17–33 %) for tPA. Conclusions: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.


VASA ◽  
2011 ◽  
Vol 40 (4) ◽  
pp. 327-332 ◽  
Author(s):  
Gabrielli ◽  
Rosati ◽  
Vitale ◽  
Millarelli ◽  
Siani ◽  
...  

Venous aneurysms are uncommon but they can have devastating consequences, including pulmonary embolism, other thromboembolic events and death. We report six cases of venous aneurysm of the extremities, in which the first sign of presence was acute pulmonary embolism. Surgical resection is recommended whenever possible. Our experience suggests that prophylactic surgery is cautiously recommended for low-risk patients with venous aneurysms of the abdomen and strongly recommended for extremity deep and superficial venous aneurysms for their potential risk of developing thromboembolic complications despite adequate anticoagulation. Other venous aneurysms should be excised only if they are symptomatic or enlarging.


VASA ◽  
2016 ◽  
Vol 45 (2) ◽  
pp. 149-154 ◽  
Author(s):  
Jie Li ◽  
Lei Feng ◽  
Jiangbo Li ◽  
Jian Tang

Abstract. Background: The aim of this meta-analysis was to evaluate the diagnostic accuracy of magnetic resonance angiography (MRA) for acute pulmonary embolism (PE). Methods: A systematic literature search was conducted that included studies from January 2000 to August 2015 using the electronic databases PubMed, Embase and Springer link. The summary receiver operating characteristic (SROC) curve, sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) as well as the 95 % confidence intervals (CIs) were calculated to evaluate the diagnostic accuracy of MRA for acute PE. Meta-disc software version 1.4 was used to analyze the data. Results: Five studies were included in this meta-analysis. The pooled sensitivity (86 %, 95 % CI: 81 % to 90 %) and specificity (99 %, 95 % CI: 98 % to 100 %) demonstrated that MRA diagnosis had limited sensitivity and high specificity in the detection of acute PE. The pooled estimate of PLR (41.64, 95 % CI: 17.97 to 96.48) and NLR (0.17, 95 % CI: 0.11 to 0.27) provided evidence for the low missed diagnosis and misdiagnosis rates of MRA for acute PE. The high diagnostic accuracy of MRA for acute PE was demonstrated by the overall DOR (456.51, 95 % CI: 178.38 - 1168.31) and SROC curves (AUC = 0.9902 ± 0.0061). Conclusions: MRA can be used for the diagnosis of acute PE. However, due to limited sensitivity, MRA cannot be used as a stand-alone test to exclude acute PE.


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