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1.
BMJ Case Rep ; 15(3)2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1745764

ABSTRACT

Pulmonary embolism (PE) is frequently encountered in the emergency department. Syncope, often as a consequence of impending haemodynamic collapse, is associated with increased mortality. While loss of consciousness owing to cerebral hypoperfusion and reduced left ventricular preload is a common cause of collapse with large volume PE, other syndromes can also cause neurological deficit in thromboembolic disease. Here, we describe a case of a woman in her 60s, presenting to the emergency department with features of high-risk PE. During clinical examination, the patient collapsed and became unresponsive with a Glasgow Coma Scale of 4/15 despite normal haemodynamics. Neurological signs were noted and CT revealed evidence of a large territory cerebral infarction. Further cardiovascular investigations identified a grade 4 patent foramen ovale. We describe a challenging case of established venous thromboembolism complicated by paradoxical embolism, highlighting the importance of thorough clinical examination and investigation and discuss the current evidence base of treatments.


Subject(s)
Embolism, Paradoxical , Foramen Ovale, Patent , Pulmonary Embolism , Venous Thromboembolism , Embolism, Paradoxical/complications , Embolism, Paradoxical/diagnostic imaging , Female , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/diagnostic imaging , Hemodynamics , Humans , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Venous Thromboembolism/complications
2.
BMJ Open ; 12(3): e060000, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1736074

ABSTRACT

INTRODUCTION: More than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%-0.5% fatal PE, and over 1000 deaths. Antithrombotic prophylaxis is standard of care but evidence is limited and conflicting. We will compare effectiveness of three commonly used chemoprophylaxis agents to prevent all-cause mortality (ACM) and clinical venous thromboembolism (VTE) while avoiding bleeding complications. METHODS AND ANALYSIS: Pulmonary Embolism Prevention after HiP and KneE Replacement is a large randomised pragmatic comparative effectiveness trial with non-inferiority design and target enrolment of 20 000 patients comparing aspirin (81 mg two times a day), low-intensity warfarin (INR (International Normalized Ratio) target 1.7-2.2) and rivaroxaban (10 mg/day). The primary effectiveness outcome is aggregate of VTE and ACM, primary safety outcome is clinical bleeding complications, and patient-reported outcomes are determined at 1, 3 and 6 months. Primary data analysis is per protocol, as preferred for non-inferiority trials, with secondary analyses adherent to intention-to-treat principles. All non-fatal outcomes are captured from patient and clinical reports with independent blinded adjudication. Study design and oversight are by a multidisciplinary stakeholder team including a 10-patient advisory board. ETHICS AND DISSEMINATION: The Institutional Review Board of the Medical University of South Carolina provides central regulatory oversight. Patients aged 21 or older undergoing primary or revision hip or knee replacement are block randomised by site and procedure; those on chronic anticoagulation are excluded. Recruitment commenced at 30 North American centres in December 2016. Enrolment currently exceeds 13 500 patients, representing 33% of those eligible at participating sites, and is projected to conclude in July 2024; COVID-19 may force an extension. Results will inform antithrombotic choice by patients and other stakeholders for various risk cohorts, and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants. TRIAL REGISTRATION: NCT02810704.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Pulmonary Embolism , Adult , Anticoagulants/therapeutic use , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , COVID-19 , Humans , Pulmonary Embolism/complications , Pulmonary Embolism/prevention & control , Randomized Controlled Trials as Topic , Young Adult
3.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
4.
Platelets ; 33(1): 48-53, 2022 Jan 02.
Article in English | MEDLINE | ID: covidwho-1541393

ABSTRACT

Coagulopathy is an evident complication of COVID-19 with predominance of a prothrombotic state. Platelet activation plays a key role. The terms "hyper-reactivity" and "hyperactivity" used in recent literature may not be clear or sufficient to explain the pathological events involved in COVID-related thrombosis (CRT). Inflammation may play a bigger role compared to thrombosis in COVID-related mortality because a smaller percentage of patients with COVID-19 die due to direct effects of thrombosis. Not all COVID-19 patients have thrombocytopenia and a few show thrombocytosis. We believe the platelet pathology is more complex than just activation or hyper-activation, particularly due to the platelets' role in inflammation. Understanding the pathology and consequences of platelets' role may help optimize management strategies and diminish CRT-associated morbidity and mortality. In this viewpoint report, we examine the published evidence of platelet hyper-reactivity in COVID-19 with a focused analysis of the key pathologies, diverse alterations, disease outcomes, and therapeutic targets. We believe that COVID-19 is a disease of inflammation and pathologic platelets, and based on the complexity and diverse pathologies, we propose the term "thrombocytopathy" as a more reflective term of the platelets' involvement in COVID-19. In our opinion, thrombocytopathy is the unpredictable pathologic alterations of platelets in function, morphology and number, caused by different factors with a variety of presentations.


Subject(s)
Blood Platelets/pathology , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Pulmonary Embolism/complications , SARS-CoV-2/pathogenicity , Abciximab/therapeutic use , Acute Disease , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Platelets/drug effects , Blood Platelets/virology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Clopidogrel/therapeutic use , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Fibrinolytic Agents/therapeutic use , Humans , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Platelet Activation/drug effects , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , Pulmonary Embolism/virology , Treatment Outcome
6.
Forensic Sci Int ; 330: 111106, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1509790

ABSTRACT

OBJECTIVES: We describe the experience of a busy metropolitan medical examiner's office in the United States and share our navigation of the COVID-19 autopsy decision-making process. We describe key gross and microscopic findings that, with appropriate laboratory testing, should direct a pathologist towards a COVID-19-related cause of death. MATERIAL AND METHODS: We performed a retrospective review of 258 suspected and/or confirmed COVID-19 associated deaths that occurred between March 5, 2020, and March 4, 2021. RESULTS: A total of 62 cases due to fatal COVID-19 were identified; autopsy findings included diffuse alveolar damage, acute bronchopneumonia and lobar pneumonia, and pulmonary thromboemboli. Nine additional decedents had a nasopharyngeal swab positive for SARS-CoV-2 and a cause of death unrelated to COVID-19. Forty-seven cases with COVID-19-like symptoms showed no laboratory or histopathologic evidence of SARS-CoV-2 infection; the most common causes of death in this group were hypertensive or atherosclerotic cardiovascular disease, complications of chronic alcoholism, and pulmonary thromboemboli unrelated to infection. CONCLUSIONS: The clinical findings associated with COVID-19 are not specific; a broad differential diagnosis should be embraced when decedents present with cough or shortness of breath. An autopsy may be indicated to identify a cause of death unrelated to COVID-19.


Subject(s)
Autopsy , COVID-19/mortality , Lung/pathology , Pulmonary Embolism/complications , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , United States/epidemiology
7.
Am J Cardiol ; 160: 106-111, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1450050

ABSTRACT

The occurrence of venous thromboembolisms in patients with COVID-19 has been established. We sought to evaluate the clinical impact of thrombosis in patients with COVID-19 over the span of the pandemic to date. We analyzed patients with COVID-19 with a diagnosis of thrombosis who presented to the MedStar Health system (11 hospitals in Washington, District of Columbia, and Maryland) during the pandemic (March 1, 2020, to March 31, 2021). We compared the clinical course and outcomes based on the presence or absence of thrombosis and then, specifically, the presence of cardiac thrombosis. The cohort included 11,537 patients who were admitted for COVID-19. Of these patients, 1,248 had noncardiac thrombotic events and 1,009 had cardiac thrombosis (myocardial infarction) during their hospital admission. Of the noncardiac thrombotic events, 562 (45.0%) were pulmonary embolisms, 480 (38.5%) were deep venous thromboembolisms, and 347 (27.8%) were strokes. In the thrombosis arm, the mean age of the cohort was 64.5 ± 15.3 years, 53.3% were men, and the majority were African-American (64.9%). Patients with thrombosis tended to be older with more co-morbidities. The in-hospital mortality rate was significantly higher (16.0%) in patients with COVID-19 with concomitant non-cardiac thrombosis than in those without thrombosis (7.9%, p <0.001) but lower than in patients with COVID-19 with cardiac thrombosis (24.7%, p <0.001). In conclusion, patients with COVID-19 with thrombosis, especially cardiac thrombosis, are at higher risk for in-hospital mortality. However, this prognosis is not as grim as for patients with COVID-19 and cardiac thrombosis. Efforts should be focused on early recognition, evaluation, and intensifying antithrombotic management for these patients.


Subject(s)
COVID-19/physiopathology , Coronary Thrombosis/physiopathology , Hospital Mortality , Myocardial Infarction/physiopathology , Pulmonary Embolism/physiopathology , Stroke/physiopathology , Venous Thrombosis/physiopathology , Aged , Aged, 80 and over , COVID-19/complications , Coronary Thrombosis/complications , Female , Humans , Male , Middle Aged , Myocardial Infarction/complications , Pulmonary Embolism/complications , SARS-CoV-2 , Stroke/complications , Venous Thrombosis/complications
8.
Lancet ; 398(10307): 1257-1268, 2021 10 02.
Article in English | MEDLINE | ID: covidwho-1447236

ABSTRACT

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.


Subject(s)
Anaphylaxis/therapy , Asphyxia/therapy , Cardiopulmonary Resuscitation/methods , Heart Arrest/therapy , Hypothermia/therapy , Pregnancy Complications, Cardiovascular/therapy , Pulmonary Embolism/therapy , Wounds and Injuries/therapy , Anaphylaxis/complications , Asphyxia/complications , COVID-19/complications , COVID-19/therapy , Electric Countershock , Female , Heart Arrest/etiology , Humans , Hypothermia/complications , Intraoperative Complications/therapy , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapy , Personal Protective Equipment , Postoperative Complications/therapy , Practice Guidelines as Topic , Pregnancy , Pulmonary Embolism/complications , Return of Spontaneous Circulation , SARS-CoV-2 , Wounds and Injuries/complications
9.
J Emerg Med ; 61(5): e103-e107, 2021 11.
Article in English | MEDLINE | ID: covidwho-1392400

ABSTRACT

BACKGROUND: Acute respiratory compromise caused by complications of COVID-19, such as acute respiratory distress syndrome (ARDS) or thromboembolic disease, is a complex syndrome with unique challenges in treatment. Management often requires time and intensive care through a multiprofessional, multispecialty approach. Initial management is particularly challenging within the limited-resource environment of the emergency department (ED). The emergency physician's toolbox of treatments with reasonably rapid onset remains limited to respiratory support, prone positioning, steroids, and anticoagulation. CASE REPORT: We present a case of a patient with COVID-19 complicated by ARDS and bilateral pulmonary emboli with severe right ventricular dysfunction and systemic hypotension treated with nebulized nitroglycerin and systemic thrombolytic therapy in the ED. Serial evaluation of right ventricular function using point of care ultrasound over the next 2 h showed improvement of function with both agents as well as improvement in the patient's respiratory rate and work of breathing. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case describes a novel use of a widely available medication for patients with COVID-19-induced right ventricular dysfunction. Nebulized nitroglycerin may be an option to improve right ventricular function when other inhaled pulmonary vasodilators are not available in the initial ED setting. © 2021 Elsevier Inc.


Subject(s)
COVID-19 , Pulmonary Embolism , Respiratory Distress Syndrome , Ventricular Dysfunction, Right , Humans , Nitroglycerin/therapeutic use , Pulmonary Embolism/complications , Pulmonary Embolism/drug therapy , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Thrombolytic Therapy , Ventricular Dysfunction, Right/drug therapy , Ventricular Dysfunction, Right/etiology
11.
Nucl Med Rev Cent East Eur ; 24(2): 120-121, 2021.
Article in English | MEDLINE | ID: covidwho-1372126

ABSTRACT

SARS-CoV-2 (COVID-19) infection is a current public health problem that has been shown to cause multiple complications, including pulmonary thromboembolism. The first presented case is a 59-year-old woman with a history of COPD, paroxysmal atrial fibrillation and COVID-19 infection in September 2020, consultation in December 2020 for atypical chest pain with suspected PE, AngioCT of pulmonary vessels was performed negative for emboli, subsequently [99mTc]Tc MAA SPECT/CT was indicated with a report of multiple triangular defects concerning acute pulmonary thromboembolism. A second case is a 70-year-old man with a history of dyslipidaemia, presented COVID-19 infection in September 2020 with a complication of PE with involvement of the left pulmonary artery, followed by [99mTc]Tc MAA SPECT/CT report multiple triangular and not triangles defects concerning pulmonary thromboembolism with signs of reperfusion.


Subject(s)
COVID-19/complications , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Single Photon Emission Computed Tomography Computed Tomography , Technetium Tc 99m Aggregated Albumin , Female , Follow-Up Studies , Humans , Middle Aged
12.
Stroke ; 52(11): e706-e709, 2021 11.
Article in English | MEDLINE | ID: covidwho-1371922
13.
J Investig Med High Impact Case Rep ; 9: 23247096211024027, 2021.
Article in English | MEDLINE | ID: covidwho-1369483

ABSTRACT

Ventricular noncompaction is a rare, heterogeneous cardiomyopathy characterized by marked trabeculations and deep intertrabecular spaces with clinical sequelae of heart failure, arrhythmias, and cardioembolic events. In this article, we describe a patient with isolated right ventricular noncompaction who presented with submassive pulmonary embolism, which was managed with long-term direct oral anticoagulation.


Subject(s)
Cardiomyopathies , Heart Failure , Pulmonary Embolism , Cardiomyopathies/complications , Cardiomyopathies/diagnostic imaging , Heart Failure/etiology , Heart Ventricles/diagnostic imaging , Humans , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging
14.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363677

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
15.
Ann Vasc Surg ; 77: 79-82, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1356137

ABSTRACT

A rare case of aortic thrombosis in a young COVID-19 positive patient is presented in this case report. Arterial thrombosis developed despite the administration of anticoagulants for treating DVT and PE. The patient underwent axillobifemoral bypass surgery. Limited surgical surveillance, administered steroids and critical health status resulted in wound site infection and consequent graft removal. Aortic endarterectomy and autovenous-patch plasty were performed after the patient's condition improved. Etiopathogenesis of arterial events in the setting of COVID-19 is not entirely understood. It has been suggested that SARS-CoV-2 infection strongly affects vascular endothelial glycocalyx (VEGLX), causes systemic inflammation - reactive microvascular endotheliosis (SIRME), and consequently results in arterial thrombosis.


Subject(s)
Aorta, Thoracic , Aortic Diseases/etiology , COVID-19/complications , Pulmonary Embolism/complications , Rare Diseases , Thrombosis/etiology , Venous Thrombosis/complications , Aortic Diseases/diagnosis , Aortic Diseases/surgery , Computed Tomography Angiography , Endarterectomy/methods , Endovascular Procedures/methods , Humans , Male , Middle Aged , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , SARS-CoV-2 , Thrombosis/diagnosis , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy
18.
Kardiologiia ; 61(6): 28-34, 2021 Jul 01.
Article in Russian, English | MEDLINE | ID: covidwho-1328332

ABSTRACT

Aim    To present clinical observations of the novel coronavirus infection (COVID-19) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after a surgical intervention in the form of thromobendarterectomy from pulmonary artery branches.Material and methods    The Acad. E.N. Meshalkin National Medical Research Center performed 127 open surgical interventions for CTEPH in the form of thromobendarterectomy from 2016 through 2020. The present study enrolled 113 patients included into the follow-up care group and into the Center Registry who were followed up for more than 6 months after the surgery. Clinical and functional features of COVID-19 were evaluated in the studied group.Results    In the follow-up care group, 5 (4.4%) postoperative CTEPH patients had COVID-19. One patient had asymptomatic disease, and others had typical clinical symptoms and bilateral polysegmental pneumonia. There were no cases requiring artificial ventilation and no lethal outcomes. All patients with COVID-19 received anticoagulants as a basis therapy for CTEPH, and two patients who had residual pulmonary arterial hypertension (PAH) additionally received a PAH-specific therapy. During the treatment of COVID-19, no adjustment of the anticoagulant or PAH-specific therapy was required.Conclusion    The group of patients with CTEPH is a unique pathophysiological model for studying the effect of COVID-19 under the conditions of compromised pulmonary circulation. In the studied follow-up care group, the COVID-19 morbidity was 4.4 % without fatal outcomes. Evaluation of the role of chronic anticoagulant and PAH-specific therapy in COVID-19 postoperative patients as well as evaluation of the role of COVID-19 in CTEPH progression merit further investigation.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Pulmonary Embolism , Chronic Disease , Humans , Hypertension, Pulmonary/etiology , Pulmonary Embolism/complications , SARS-CoV-2
19.
Sci Rep ; 11(1): 14015, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301182

ABSTRACT

Venous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in ~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main findings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients. The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing sets, respectively. A GWAS on the LIME approximate identified a strong statistical association peak (rs1424597: p = 5.3 × 10-7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%, p = 0.005) and the EOVT (3% vs. 0%, p = 0.013) studies. In a sample of 112 COVID-19 patients known to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4 levels were associated (p = 0.025) with worsened respiratory function. Using an original integrated proteomics and genetics strategy, we identified PLXNA4 as a new susceptibility gene for PE whose exact role now needs to be further elucidated.


Subject(s)
Genetic Predisposition to Disease/genetics , Neural Networks, Computer , Proteomics , Pulmonary Embolism/blood , Pulmonary Embolism/genetics , Receptors, Cell Surface/blood , Receptors, Cell Surface/genetics , Adult , COVID-19/complications , Female , Genome-Wide Association Study , Humans , Male , Phenotype , Polymorphism, Single Nucleotide , Pulmonary Embolism/complications , Pulmonary Embolism/metabolism
20.
BMJ Case Rep ; 14(6)2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1266369

ABSTRACT

A 61-year-old obese man who had recently tested positive for COVID-19 presented to the emergency department following an unwitnessed collapse, with a brief period of unresponsiveness. CT pulmonary angiography confirmed the presence of extensive bilateral pulmonary embolism despite the patient reporting full compliance with long-term dabigatran. The patient was initially anticoagulated with low-molecular-weight heparin and was treated with non-invasive ventilation and dexamethasone for COVID-19 pneumonia. He made a full recovery and was discharged on oral rivaroxaban. His case highlighted some of the common problems encountered when selecting an anticoagulation strategy for obese patients, as well as the lack of definitive evidence to guide treatment decisions. These challenges were further complicated by our incomplete understanding of the underlying mechanisms of COVID-19 coagulopathy, with limited data available regarding the optimal management of thromboembolic complications.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants/adverse effects , Humans , Male , Middle Aged , Obesity/complications , Pulmonary Embolism/complications , Pulmonary Embolism/drug therapy , SARS-CoV-2 , Venous Thromboembolism/complications , Venous Thromboembolism/drug therapy
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