Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism

2020 ◽  
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Agnieszka Janion-Sadowska ◽  
Agnieszka Metzgier-Gumiela ◽  
Mateusz Polak ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Thrombus Formation ◽  
Pulmonary Arteries ◽  
Fibrin Clot ◽  
Sem Analysis ◽  
Clot Lysis ◽  
Vein Thrombosis ◽  
The Impact ◽  
Increased Susceptibility

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.

scholarly journals Prothrombotic Fibrin Clot Phenotype in Patients with Deep Vein Thrombosis and Pulmonary Embolism: A New Risk Factor for Recurrence

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Anetta Undas
Keyword(s):  
Pulmonary Embolism ◽  
Risk Factor ◽  
Deep Vein Thrombosis ◽  
Venous Thrombosis ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Postthrombotic Syndrome ◽  
Vein Thrombosis ◽  
And Function ◽  
Deep Vein

Prothrombotic fibrin clot phenotype, involving faster formation of dense meshwork composed of thinner and highly branched fibers that are relatively resistant to plasmin-induced lysis, has been reported in patients with not only myocardial infarction or stroke, but also venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT), and/or pulmonary embolism (PE). Prothrombotic fibrin clot phenotype, in particular prolonged clot lysis time, is considered a novel risk factor for VTE as well as venous thrombosis at unusual location, for example, cerebral sinus venous thrombosis, retinal vein obstruction, and Budd-Chiari syndrome. Growing evidence from observational studies indicates that abnormal fibrin clot properties can predict recurrent DVT and PE and they are involved in serious complications of VTE, for example, thromboembolic pulmonary hypertension and postthrombotic syndrome. The purpose of this article is to review our current understanding of the role of fibrin clot structure and function in venous thrombosis with emphasis on clinical issues ranging from prognosis to therapy.

Fibrinolysis in Venous Thromboembolism

2021 ◽  
Author(s):  
Anetta Undas
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Evidence ◽  
Pulmonary Arteries ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Recurrent Deep Vein Thrombosis ◽  
Deep Vein

AbstractFibrinolysis is of paramount importance in maintaining or regaining the patency of veins and pulmonary arteries obstructed by thrombi. Growing experimental and clinical evidence indicates that impaired fibrinolysis mediated by multiple complex mechanisms is involved in venous thromboembolism (VTE). Global plasma fibrin clot lysis markers, especially clot lysis time, have been reported to predict recurrent deep-vein thrombosis and pulmonary embolism. The current overview summarizes available data linking fibrinolysis to VTE and its long-term sequelae.

scholarly journals Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated with Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation

2020 ◽  
Vol 9 (4) ◽  
pp. 953 ◽  
Author(s):  
Michał Ząbczyk ◽  
Joanna Natorska ◽  
Agnieszka Janion-Sadowska ◽  
Krzysztof P. Malinowski ◽  
Marianna Janion ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Fibrin Clot ◽  
Neutrophil Extracellular Trap ◽  
Clot Lysis ◽  
Elevated Plasma ◽  
Lactate Levels ◽  
Acute Pe ◽  
Elevated Lactate ◽  
Pai 1

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.

On postpartum pulmonary embolism

1934 ◽  
Vol 30 (10) ◽  
pp. 1027-1029
Author(s):  
A. I. Petchenko
Keyword(s):  
Pulmonary Embolism ◽  
Blood Flow ◽  
Blood Loss ◽  
Postpartum Period ◽  
Vascular Tone ◽  
Thrombus Formation ◽  
Obstetrics And Gynecology ◽  
Vascular Thrombosis ◽  
Vein Thrombosis

Vascular thrombosis in obstetrics and gynecology is quite common, although not always easy to recognize. In the postpartum period, after many vaginal operations we have massive thrombus formation. Placental vein thrombosis is almost physiological; slowed blood flow, decreased vascular tone after the fetus emerges, blood loss are predisposing moments to thrombosis formation in the postpartum period.

scholarly journals Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Hua Chen ◽  
Dongxia Liu ◽  
Lan Ge ◽  
Tao Wang ◽  
Zhenzhen Ma ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Thrombus Formation ◽  
Vascular Dysfunction ◽  
In Vivo Model ◽  
Protective Effects ◽  
Inhibitory Peptide ◽  
Endothelial Inflammation

AbstractCatestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

Abstract 14499: Impact of Pre-existing and New Incident Atrial Fibrillation on Outcomes of Patients With Acute Pulmonary Embolism: Findings From an International Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Behnood Bikdeli ◽  
David Jimenez ◽  
Jorg Del Toro ◽  
Gregory Piazza ◽  
Augussina Rivas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Embolism ◽  
Ischemic Stroke ◽  
Acute Pulmonary Embolism ◽  
Adverse Outcomes ◽  
Risk Of Mortality ◽  
Patient Groups ◽  
The Impact ◽  
Related Mortality

Background: Atrial fibrillation (AF) may occur prior to or early in the course of acute pulmonary embolism (PE). The impact of AF on outcomes of patients with PE remains uncertain. Methods: Using the data from a large prospective multicenter registry of patients with objectively-confirmed PE (04/2014 to 01/2020), we identified three patient groups: 1) those with pre-existing AF 2) patients with newly identified AF within 2 days from the index PE (incident AF) and 3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, in unadjusted and multivariable adjusted models considering those without AF as referent. Results: Among 16,497 patients with PE, 792 had pre-existing AF. Compared with those without AF, patients with pre-existing AF, had increased odds of 90-day all-cause (Odds ratio [OR]: 2.81 (95% confidence interval [CI]: 2.33-3.38) and PE-related mortality (OR: 2.38, 95% CI: 1.37-4.14). After multivariable adjustment, pre-existing AF significantly increased the odds of all-cause mortality (OR: 1.91, 95% CI: 1.57-2.32) but not PE-related mortality (OR: 1.50; 95% CI: 0.85-2.66). Pre-existing AF was associated with increased hazard for ischemic stroke at 1-year follow-up (hazard ratio [HR]: 5.48; 95% CI: 3.10-9.69). Among 16,497 patients with PE, 445 developed incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR: 2.28; 95% CI: 1.75-2.97) and PE-related (OR: 3.64; 95% CI: 2.01-6.59) mortality. Findings were similar in multivariable analyses and at 1-year follow-up (Figure). No patients with incident AF developed ischemic stroke. Conclusion: In patients with acute symptomatic PE, both pre-existing AF and incident AF predict an adverse clinical course, although the type of adverse outcomes may be different depending on the timing of AF onset.

Altered fibrin clot structure contributes to thrombosis risk in severe COVID-19

2021 ◽  
Author(s):  
Malgorzata Wygrecka ◽  
Anna Birnhuber ◽  
Benjamin Seeliger ◽  
Laura Michalick ◽  
Oleg Pak ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Factor Xii ◽  
Tissue Sections ◽  
Thrombosis Risk ◽  
Activation Rate ◽  
Activation Products ◽  
Kaolin Clotting Time ◽  
Clot Structure

The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in two independent cohorts of critically ill COVID-19 patients in comparison to patients suffering from severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the kaolin clotting time was not prolonged in COVID-19 as compared to ARDS-influenza. Using confocal and electron microscopy, we show that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, we observed clot lysis in 30% of COVID-19 patients and 84% of ARDS influenza subjects. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19. Together, our results indicate that elevated fibrinogen levels and increased FXII activation rate promote thrombosis and thrombolysis resistance via enhanced thrombus formation and stability in COVID-19.

scholarly journals Impact of persistent anaemia on mortality in patients hospitalised with acute pulmonary embolism: an Australian retrospective observational study

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e027112
Author(s):  
Wallace Chow ◽  
Christopher Wong ◽  
Jerrett K Lau ◽  
Vincent Chow ◽  
Leonard Kritharides ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Observational Study ◽  
Acute Pulmonary Embolism ◽  
Retrospective Observational Study ◽  
Study Cohort ◽  
Prognostic Impact ◽  
Tertiary Referral Centre ◽  
Baseline Haemoglobin ◽  
The Impact ◽  
Acute Pe

ObjectivesAnaemia is associated with increased mortality in acute pulmonary embolism (PE) patients. However, prior studies have not examined the prognostic impact of trends in plasma haemoglobin during admission. This study investigates the impact of changes in haemoglobin level on mortality during hospital stay in acute PE.Study designA retrospective observational study.SettingTertiary-referral centre in Australia.ParticipantsConsecutive patients from 2000 to 2012 admitted with confirmed acute PE were identified from a dedicated PE database. Haemoglobin levels on days 1, 3–4, 5–6 and 7 of admission were retrieved. Patients without both baseline haemoglobin and subsequent haemoglobin levels were excluded (n=327), leaving 1099 patients as the study cohort. Anaemia was defined as haemoglobin <130 g/L for men and <120 g/L for women. There were 576 patients without anaemia throughout admission, 65 with transient anaemia (anaemic on day 1, but subsequently normalised during admission), 122 with acquired anaemia (normal on day 1 but developed anaemia during admission) and 336 with persistent anaemia. A total of 71 patients received blood transfusion during admission.Main outcome measure6-month mortality was tracked from a state-wide death database and analysed using multivariable modelling.ResultsAfter adjusting for transfusion, patietns with persistent anaemia had a significantly increased 6-month mortality risk (adjusted HR 1.97, 95% CI 1.26 to 3.09, p=0.003) compared with patients without anaemia. There was no difference in mortality between patients with transient or acquired anaemia and patients without anaemia.ConclusionAmong patients who had anaemia during their admission for acute PE, only the subgroup with persistent anaemia demonstrated worse outcomes.

scholarly journals P1267 Negative baseline diagnostic imaging does not exclude pulmonary embolism in patients with reccurrent syncope

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
U Kocabas ◽  
H Altay ◽  
F Ozkalayci ◽  
I Isiklar ◽  
S Pehlivanoglu
Keyword(s):  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Doppler Ultrasound ◽  
Ultrasound Imaging ◽  
Normal Sinus Rhythm ◽  
Pulmonary Arteries ◽  
Vein Thrombosis ◽  
Normal Sinus ◽  
Doppler Ultrasound Imaging ◽  
Deep Vein

Abstract INTRODUCTION In patients who are admitted to a hospital due to episode of syncope, acute pulmonary embolism (PE) is rarely considered as a possible cause. This report presents two cases illustrating PE as a cause of syncope with elevated cardiac troponin (cTn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels despite normal echocardiographic examination and negative Doppler ultrasound imaging. Case 1: An 83-year-old woman admitted to the ER due to episodes of recurrent syncopes. According to her anamnesis, she had four episodes of syncopes during last three weeks without chest pain, dyspnea, palpitation or hemoptysis. ECG revealed a normal sinus rhythm with a heart rate of 70 bpm without ischemic changes. Laboratory tests revealed raised levels of cTn and NT-proBNP. Transthoracic echocardiography (TTE) demonstrated preserved left and right ventricular systolic functions without any cardiac chamber enlargement and mild tricuspid regurgitation with a PAP of 35 mmHg. Patient’s pre-test probability for pulmonary embolism was low (Wells’ score &lt; 2) but D-dimer level was elevated. Doppler imaging for detection of deep vein thrombosis was negative. Computed tomography pulmonary angiography (CTPA) showed filling defects in the pulmonary arteries consistent with pulmonary embolism (Panel A). The patient was discharged with rivaroxaban therapy without any complication. Case 2: A 69- year-old woman presented to ER with symptoms of chest pain and recurrent episodes of syncope for the last 2 days. Her medical history revealed hypertension and hyperlipidemia. On admission ECG showed a normal sinus rhythm with a heart rate of 105 bpm and T-wave inversions in inferior leads. Laboratory tests showed elevated levels of cTn and NT-proBNP. TTE demonstrated normal left ventricular systolic function with an ejection fraction of 55% and normal right ventricular function and chamber size with a tricuspid annular plane systolic excursion of 22 mm. Diagnostic coronary angiography was performed to exclude acute ischemia revealed non-significant coronary artery stenosis. Doppler ultrasound imaging for detection of deep vein thrombosis was negative. CTPA showed filling defects in the bilateral main pulmonary arteries consistent with acute bilateral pulmonary embolism (Panel B-C). The patient was discharged with rivaroxaban therapy after four days of hospitalization period without any complication. CONCLUSION Elevated cTn and NT-proBNP leves on admission strongly suggest transient hemodynamic impairment causing cardiac injury and syncope. Normal admission ECG and TTE can exclude most possible acute cardiac causes of syncope. Although acute right ventricular dsyfunction is the most frequent finding of acute massive PE causing hemodymanic impairment resulting with syncope, diagnosis of acute PE should only be excluded with CTPA in patients with similar clinical characteristics despite normal TTE and negative venous Doppler ultrasound imaging. Abstract P1267 Figure

P2769Racial differences in outcomes among acute pulmonary embolism patients: a nationwide analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Shi
Keyword(s):  
Pulmonary Embolism ◽  
Regression Analysis ◽  
Length Of Stay ◽  
Hospital Mortality ◽  
Acute Pulmonary Embolism ◽  
Primary Diagnosis ◽  
Total Cost ◽  
Rehabilitation Facilities ◽  
The Impact ◽  
White Patients

Abstract Background Limited data is available regarding racial disparities in patients admitted for acute pulmonary embolism. Purpose We aimed to examine the impact of racial differences on outcomes in patients admitted for acute pulmonary embolism. Methods We used the Nationwide Inpatient Sample, which represents 20% of community hospital discharges in the US, to identify adult patients who were discharged with the primary diagnosis of acute pulmonary embolism in 2016 with ICD-10 codes. Logistic regression analysis and linear regression analysis were used to compare patients with different races. Outcomes were focused on in-hospital mortality, total cost, length of stay and disposition, adjusting gender, age, Charlson comorbid index and socioeconomic variables. Results In 2016, 35,526 patients were admitted with a primary diagnosis of acute pulmonary embolism. White patients were more likely to be older and with higher income. After adjusting for the above variables, white patients had lower total cost of hospitalization (p<0.0001), shorter length of stay (p<0.0001), lower in-hospital mortality (adjusted odds ratio = 0.79, p=0.001), and more likely to be discharged to rehabilitation facilities compared to being discharged home. Outcomes in white vs non-white patients Conclusion Among acute pulmonary embolism hospitalizations, white patients generally had better outcomes despite being older in age, and were more likely to be transferred to rehabilitation facilities after discharge.

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