High-Altitude Pulmonary Embolism: Epidemiology, Pathophysiology, Diagnosis, and Management

1. Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust 2. Lane Fox Respiratory Unit, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust 3. Department of Haematology, North Middlesex Hospital 4. Department of Paediatric Haematology, Bristol Royal Hospital for Children 5. Department of Haematological Medicine, King’s College Hospital 6. Department of Haematology, Whittington Hospital

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract).Key Points• The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps.• Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications.• This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction.Graphical abstractCovid-19 and systemic lupus erythematosus—potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery).

Expanding the Clinical Spectrum of OSA — An Association with Pulmonary Embolism?

75-Year-Old Woman With Chest Pain and Shortness of Breath

Acquired and Hereditary Hypercoagulable States in Patients with Continuous Flow Left Ventricular Assist Devices: Prevalence and Thrombotic Complications

Hyperhomocysteinemia as a hypercoagulable state has been debatable, but when associated with other high-risk factors like severe vitamin B12 and folate deficiency, smoking, high altitude, and antiphospholipid syndrome can present with thromboembolism. Vegans are at high risk of severe B12 deficiency as the primary source is animal products. Right now, the total number of vegans, vegetarians, and all related categories, is close to 14 per cent of the world population. We here present a young vegan with severe B12 deficiency presenting with sub-massive thromboembolism.

High altitude pulmonary oedema: who gets it and why?

Introduction and aim. A small number of critically ill patients with coronavirus disease (COVID-19) develop thromboembolism (arterial or venous), both micro- and macrovascular complications such as deep vein thrombosis, pulmonary embolism, and pulmonary arterial thrombosis. The objective of the study is to describe the pathophysiology of venous thromboembolism in patients with COVID-19. Material and methods. In this article a narrative review regarding pathophysiology of thromboembolism in patients with COVID-19. Analysis of the literature. The development of coagulopathy is a consequence of the intense inflammatory response associated with hypercoagulability, platelet activation, and endothelial dysfunction. The pathophysiology that relates pulmonary thromboembolism (PTE) with COVID-19 is associated with a hypercoagulable state. PTE is suspected in hospitalized patients presenting dyspnea, decreased oxygen requirement, hemodynamic instability, and dissociation between hemodynamic and respiratory changes. In COVID-19-associated coagulopathy, initially, patients present with elevated levels of fibrinogen and D-dimer, with minimal changes in prothrombin time and platelet count. The main risk factor for the development of pulmonary embolism is the increase in D-dimer that is associated with the development of PTE. The administration of iodine-based contrast agent to patients with COVID-19 would affect P-creatinine and renal function, where Ultrasound is viewed as cost-effective and highly portable, can be performed at the bedside. Conclusion. Acute respiratory distress syndrome severity in patients with COVID-19 can explain PTE as a consequence of an exaggerated immune response.

Placental hypoxia, a major component of the pathophysiology of preeclampsia, is associated with various maternal vascular and endothelial dysfunctions. The higher incidence of preeclampsia at high altitude remains incompletely explained. The aim of the present study was to investigate the effect of high altitude on some endothelial and vascular dysfunction markers in normal and preeclamptic pregnancies. Eighty pregnant women (Paras 2-4) were enrolled in this study, which included four groups (each n = 20): normal pregnancies at low altitude (NL), normal pregnancies at high altitude (NH), preeclamptic pregnancies at low altitude (PL), and preeclamptic pregnancies at high altitude (PH). In normal pregnancies at high altitude serum ET-1, plasma TXA2, and serum TNF-α levels increased significantly with a significant reduction in plasma PGI2 (66.81 ± 7.36, 122.86 ± 13.37, 102.23 ± 13.31, 191.57 ± 19.68, respectively) compared with the NL group (48.92 ± 4.58, 89.03 ± 10.67, 69.86 ± 7.97, 238.01 ± 24.55, respectively). In preeclampsia at low altitude serum ET-1, plasma TXA2, and serum TNF-α levels increased significantly with a significant reduction in plasma PGI2 (88.39 ± 9.54, 162.73 ± 15.92, 142.39 ± 15.37, 149.155 ± 15.66, respectively) compared with both NL and NH groups. High altitude significantly augmented these changes in preeclamptic patients (117.75 ± 12.96, 211.01 ± 22.69, 196.86 ± 17.64, 111.92 ± 10.74) compared with PL, NH and NL groups. In conclusion hypoxia at high altitude aggravated the disturbances in the levels of ET-1, TXA2, PGI2 and TNF-α associated with preeclampsia. This may contribute to the higher risk of preeclampsia at high altitude.

Primary pulmonary artery sarcoma in the pediatric patient: Review of literature and a case report

Clinical characteristics, risk factors and outcomes of South-East Asian patients with acute pulmonary embolism

Pregnancy associate with thromboembolism is one of leading causes of maternal morbidity and mortality. Worldwide the incidence of pregnancy related venous thromboembolism is approximately 1 in 1500 deliveries. The arterial thromboembolism risk is increased from 3 to 4 fold and the risk of venous thromboembolism is five times higher in a pregnant that in a non-pregnant woman. With an appropriate prophylaxis and therapy, prevention of death from systemic thromboembolism in pregnancy necessitates a high index of clinical suspicion succeeded by a timely and accurate diagnostic approach. In pregnancy the clinical diagnosis of systemic thromboembolism is notoriously difficult due to the overlap of signs and symptoms between the pulmonary embolus with or without deep venous thrombosis. We performed a retrospective study of 86 pregnant women with Pulmonary thromboembolism (PTE) and Deep venous thrombosis (DVT) diagnosed between 2009-2015 in Obstetrics-Gynecology Clinic 1 at Emergency County Hospital of Craiova. Our study evaluated these cases considering frequency, maternal and fetus risk associated with thromboembolism. In 6 years we had 35 women diagnosed as PTE, 8 women diagnosed as DVT and PTE, and 43 patients diagnosed as DVT. The underlying disease in our study was hypertension and the most frequent symptoms reported were dyspnea and limb swelling.(100%).During the third trimester of pregnancy the incidence of PTE was 45% and DVT 57%. 12 cases of DVT were related to thrombophilia. Also we found 25 % of PTE that occurred after cesarean and 8 % of PTE after vaginal delivery. We notice that vaginal delivery is safer than cesarean surgery. Also the importance of third trimester of pregnancy and postpartum it is evident.

Background: A Patent Foramen Ovale (PFO) is frequently associated with cryptogenic stroke in young patients with paradoxical embolism as the presumed mechanism. Moreover, hypercoagulable states that are known in the pathogenesis of venous thrombosis, can sometimes be found in patients with stroke, which can be explained by the PFO, that provides the missing link. The association between PFO and prothrombotic state may hence increase the risk for paradoxical embolism. Yet, the cause-and-effect relationship between these pathologies is not clearly established and the best therapeutic and preventive strategy are unelucidated. Case Report: We report a case associating ischemic stroke, left internal carotid occlusion, and pulmonary embolism with the discovery of a PFO and inherited thrombophilic disorders, in a young woman under combined contraceptives. Conclusion: We believe that this case is important since it shows the importance of searching for a PFO in young patients with arterial events and thrombophilia and also the interest of systematic screening for procoagulant disorders in those with stroke and PFO, and highlights the challenge in the multidisciplinary management of such patients.

Characteristics and outcomes of COVID-19-associated pulmonary embolism

A RARE CASE OF THROMBUS IN TRANSIT MIGRATION TO THE MAIN PULMONARY ARTERY IN A PATIENT WITH SUBMASSIVE PULMONARY EMBOLISM