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Fulltext COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease

Gan R, Rosoman NP, Henshaw DJE, Noble EP, Georgius P, Sommerfeld N

Med Hypotheses, 2020 Nov;144:110024.
PMID: 32758871 DOI: 10.1016/j.mehy.2020.110024

SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the "protective" angiotensin (1-7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than "cytokine storm". Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.

Matched MeSH terms: Venous Thromboembolism/complications
Antithrombotic effects of hydroxychloroquine in a pregnant patient with Antiphospholipid syndrome and recurrent venous thromboembolism

Gan SP, Ong SG

Med J Malaysia, 2017 04;72(2):124-125.
PMID: 28473677 MyJurnal

A pregnant woman with antiphospholipid syndrome presented with repeated venous thromboembolism (VTE) in the first and second trimesters of pregnancy despite receiving combination therapy with low-molecular-weight heparin and aspirin. The addition of hydroxychloroquine prevented further VTE recurrence, thus demonstrating its potential antithrombotic effects.

Matched MeSH terms: Venous Thromboembolism/complications*
Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association

Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al.

Circulation, 2019 03 05;139(10):e56-e528.
PMID: 30700139 DOI: 10.1161/CIR.0000000000000659
Matched MeSH terms: Venous Thromboembolism/complications
Adjustments to warfarin dosing after gastric bypass and sleeve gastrectomy

Strong AT, Sharma G, Nor Hanipah Z, Tu C, Brethauer SA, Schauer PR, et al.

Surg Obes Relat Dis, 2018 05;14(5):700-706.
PMID: 29496441 DOI: 10.1016/j.soard.2017.12.021

BACKGROUND: Warfarin dosing after bariatric surgery may be influenced by alterations in gastrointestinal pH, transit time, absorptive surface area, gut microbiota, food intake, and adipose tissue.
OBJECTIVES: The aim of this study was to describe trends in warfarin dosing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG).
SETTING: Single academic center.
METHODS: All patients chronically on warfarin anticoagulation before RYGB or SG were retrospectively identified. Indications for anticoagulation, history of bleeding or thrombotic events, perioperative complications, and warfarin dosing were collected.
RESULTS: Fifty-three patients (RYGB n = 31, SG n = 22) on chronic warfarin therapy were identified (56.6% female, mean 54.4 ± 11.7 yr of age). Of this cohort, 34.0% had prior venous thromboembolic events, 43.4% had atrial fibrillation, and 5.7% had mechanical cardiac valves. Preoperatively, the average daily dose of warfarin was similar in the RYGB group (8.3 ± 4.1 mg) and SG group (6.9 ± 2.8 mg). One month after surgery, mean daily dose of warfarin was reduced 24.1% in the RYGB group (P

Matched MeSH terms: Venous Thromboembolism/complications