Protein expression profiling suggests relevance of non-canonical pathways in isolated pulmonary embolism

Blood ◽  
2021 ◽  
Author(s):  
Vincent Ten Cate ◽  
Jürgen H. Prochaska ◽  
Andreas Schulz ◽  
Thomas Koeck ◽  
Alejandro Pallares Robles ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Interferon Γ ◽  
Population Based ◽  
Specific Protein ◽  
Arginine Deiminase ◽  
Alternative Pathways ◽  
Vein Thrombosis ◽  
Independent Population ◽  
Canonical Pathways ◽  
History Of

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multi-center prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n=96) against those of patients with DVT-associated PE (n=276) or isolated DVT (n=160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of five proteins: interferon-γ (IFNG), glial cell line-derived neurotrophic growth factor (GDNF), polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), peptidyl arginine deiminase type-2 (PADI2) and interleukin-15 receptor subunit α (IL-15Rα). These proteins were orthogonally validated using cis protein quantitative trait loci (cis pQTLs). External replication in an independent population-based cohort (n=5,778) further validated the proteomic results, and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years, interquartile range: 1.6 - 4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate non-canonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.

scholarly journals Atrial Fibrillation in Patients with Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Katarzyna Ptaszynska-Kopczynska ◽  
Izabela Kiluk ◽  
Bozena Sobkowicz
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Embolism ◽  
Large Scale ◽  
Negative Impact ◽  
Previous History ◽  
Cardiovascular Death ◽  
Population Based ◽  
Embolic Material ◽  
Vein Thrombosis ◽  
History Of

Pulmonary embolism (PE) is one of the most common causes of cardiovascular death. The most often PE etiology is a deep vein thrombosis (DVT) of the lower extremities, but embolic material can arise in pelvic or upper extremity veins as well as in right heart chambers. There is growing number of evidences of atrial fibrillation (AF) involvement in PE. The presence of AF in patients with PE may be both the cause and the consequence of PE. The PE association with AF should be considered in patients without confirmed DVT and with history of AF, which itself is associated with prothrombotic state. The valuable diagnostic method is echocardiography that may bring the insight into source of embolic material. Another possible AF and PE association is the AF as a consequence of an abrupt increase in pulmonary vascular resistance due to the occlusion of the pulmonary vessels. Large-scale population-based studies have provided a considerable body of evidence on the involvement of PE in the onset of subsequent AF. Another important issue is the influence of AF on prognosis in patients with PE. Most investigators demonstrated a negative impact of AF on mortality. The main problem to resolve is whether AF is an independent mortality risk factor or whether it occurs as a result of comorbidities or the severity of a PE episode. Although the pathophysiological basis of this bidirectional relationship exists, many questions are still unresolved and require further studies, including the significance of paroxysmal AF accompanying an acute PE episode, the usefulness of PE risk scales in patients with concomitant AF, and the effect of anticoagulant treatment on PE and AF occurrence. Regardless of the type of AF, clinicians should be alert to the possibility of PE in patients with previous history of AF or presenting with new-onset AF.

Diabetes increases the risk of deep-vein thrombosis and pulmonary embolism

2015 ◽  
Vol 114 (10) ◽  
pp. 812-818 ◽  
Author(s):  
Wei-Sheng Chung ◽  
Cheng-Li Lin ◽  
Chia-Hung Kao
Keyword(s):  
Pulmonary Embolism ◽  
Cohort Study ◽  
Deep Vein Thrombosis ◽  
General Population ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Vein Thrombosis ◽  
Deep Vein

SummaryWe evaluated the effects of diabetes on the risks of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) in a nationwide, population-based cohort study in Taiwan. The patients with newly diagnosed type 2 diabetes mellitus (T2DM) were identified, and DM-free controls were randomly selected from the general population and frequency-matched according to age, sex, and index year by using the records of the Longitudinal Health Insurance Database between 2000 and 2011. Both cohorts were followed up until the end of 2011 to measure the incidence of DVT and PE. We analysed the risks of DVT and PE using Cox proportional-hazards regression models. The overall incidence of VTE was higher in the T2DM patients than in the controls (12.0 vs 7.51 per 10,000 person-years). The T2DM patients exhibited a 1.44-fold adjusted hazard ratio (aHR) of VTE development compared with the controls (95 % confidence interval [CI] = 1.27–1.63). The risks of DVT (aHR = 1.43, 95 % CI = 1.23–1.65) and PE (aHR = 1.52, 95 % CI = 1.22–1.90) were greater in the T2DM than those in the controls. The T2DM patients had a substantially higher risk of DVT (aHR = 5.10, 95 % CI = 3.12–8.32) and PE (aHR = 7.50, 95 % CI = 3.29–17.1) development than the controls did in adults aged 49 years and younger. In conclusion, the longitudinal nationwide cohort study indicated that T2DM patients carried greater risks of developing VTE than did the general population.

scholarly journals Association between cardiovascular risk-factors and venous thromboembolism in a large longitudinal study of French women

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
C. J. MacDonald ◽  
A. L. Madika ◽  
M. Lajous ◽  
M. Canonico ◽  
A. Fournier ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Pulmonary Embolism ◽  
Cardiovascular Risk ◽  
Venous Thromboembolism ◽  
Cardiovascular Risk Factors ◽  
Arterial Disease ◽  
Population Based ◽  
Cox Models ◽  
Vein Thrombosis

Abstract Background Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. Methods We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. Results During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. Conclusions Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.

scholarly journals Case Report: Unprovoked venous thromboembolism in a young adult

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 182
Author(s):  
Jeyhan Dhabhar ◽  
Varshil Mehta ◽  
Nimit Desai ◽  
Sameer Dawoodi ◽  
Sojib Bin Zaman
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Trauma Surgery ◽  
Sudden Onset ◽  
Vein Thrombosis ◽  
Doppler Study ◽  
Pulmonary Angiogram ◽  
Co Morbidity ◽  
History Of ◽  
Prolonged Immobilization

A 24-year-old male was presented to us with sudden onset of chest pain and dyspnea for the past one hour. There was no history of calf pain, trauma, surgery, prolonged immobilization, long-haul air travel, bleeding diathesis or any other co-morbidity. The patient denied any addiction history. The Electrocardiogram showed tachycardia with S1Q3T3 pattern. The left arterio-venous Doppler study was suggestive of a thrombus in popliteal vein and sapheno-popliteal junction. The CT-Pulmonary Angiogram scan was suggestive of a massive pulmonary thromboembolism. The patient was thrombolysed with Intravenous Alteplase immediately and was put on tab Rivaroxaban for maintenance. He was later discharged after being stable. Unprovoked venous thromboembolism (VTE) is very rare and has the potential to lead to pulmonary embolism which could be disastrous, especially in young adults. We present such a case where unprovoked VTE was diagnosed and treated. This case suggests that high clinical suspicion is the key for the diagnosis of acute pulmonary embolism, especially in the absence of history suggestive of deep vein thrombosis.

Hypofibrinolysis in Patients with a History of Idiopathic Deep Vein Thrombosis and/or Pulmonary Embolism

1992 ◽  
Vol 67 (04) ◽  
pp. 397-401 ◽  
Author(s):  
Vito Grimaudo ◽  
Fedor Bachmann ◽  
Jacques Hauert ◽  
Maria-Adele Christe ◽  
Egbert K O Kruithof
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Vein Thrombosis ◽  
Molar Excess ◽  
History Of ◽  
Deep Vein ◽  
Pai 1

SummaryAn impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers.The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA: Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%).To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1: Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.

Abstract TMP74: Stroke And Pulmonary Embolism, Clinical Features, Risk Factors And Outcome

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
jitphapa pongmoragot ◽  
Alejandro Rabinstein ◽  
Yongchai Nilanont ◽  
Daniel Selchen ◽  
Rick Swartz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Length Of Stay ◽  
Predisposing Factors ◽  
P Value ◽  
Stroke Patients ◽  
Vein Thrombosis ◽  
History Of ◽  
Deep Vein

Introduction: Pulmonary embolism (PE) is an uncommon medical complication after stroke. Predisposing factors include deep vein thrombosis (DVT) in patients with hemiplegia or an underlying hypercoagulable state. However, little information is known regarding PE in stroke patients. Objective: We evaluated clinical characteristics, predisposing factors, and outcomes in stroke patients who developed PE. Methods: We included patients with an acute ischemic stroke (AIS) admitted to the participating institutions in the Registry of the Canadian Stroke Network between 2003 to 2008. Pulmonary embolism was diagnosed by nuclear imaging within 30 days of the stroke case index. Demographic data and clinical variables were collected. Logistic regression and survival analyses were completed to determine the association of risk factors with the outcomes of interest. Outcome Measures: primary outcome was death or disability at discharge defined as the modified Rankin scale >3. Secondary outcomes include admission to the Intensive Care Unit, disposition, and length of hospital stay, death at 3 months and at 1 year. Results: Among 11,287 patients with AIS, PE was found in 89 (0.78%) of patients. The development of PE was associated with higher risk of death in 30 days (25.8%vs 13.6%;p <0.001) and 1 year, (47.2% vs 24.6%;p <0.001). Disability was also more common in stroke patients with PE (85.4% vs 63.6% without PE; p <0.001). Mean length of stay was longer in stroke patients with PE (36 vs 16 days; p<0.001). Past medical history of cancer or deep vein thrombosis, history of cardiac arrest or deep vein thrombosis during admission were associated with PE. After adjustment, PE was associated with lower survival at 30 days (p value = 0.0012) and 1 year (p value < 0.0001) (Figures 1 & 2 represent survival function). Conclusions: In this large study, PE occurs in approximately 1% of AIS patients. PE was associated with higher disability, longer length of stay and lower short and long-term survival.

A population-based cohort study on deep vein thrombosis and pulmonary embolism among schizophrenia patients

2015 ◽  
Vol 162 (1-3) ◽  
pp. 248-252 ◽  
Author(s):  
Wen-Yu Hsu ◽  
Hsien-Yuan Lane ◽  
Cheng-Li Lin ◽  
Chia-Hung Kao
Keyword(s):  
Pulmonary Embolism ◽  
Cohort Study ◽  
Deep Vein Thrombosis ◽  
Population Based ◽  
Vein Thrombosis ◽  
Deep Vein
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