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At the Trump presser, maybe someone should ask about clotting/thrombosis? Read up on the topic here…
Thrombosis and COVID-19 pneumonia: the clot thickens!
https://erj.ersjournals.com/content/early/2020/06/04/13993003.01608-2020
Pulmonary thrombosis appears to be common in Covid-19 pneumonia and takes two forms, proximal pulmonary emboli and/or distal thrombosis. We hypothesise mechanisms and discuss clinical implications.
At the end of last year, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an acute respiratory illness epidemic in Wuhan, China [1, 2]. The World Health Organisation (WHO) termed this illness Coronavirus Disease 2019 (COVID-19). The coronavirus family have been shown to enter cells through binding angiotensin-converting enzyme 2 (ACE2), found mainly on alveolar epithelium and endothelium. Activation of endothelial cells is thought to be the primary driver for the increasingly recognised complication of thrombosis. Viral inclusion bodies have been identified in endothelial cells in a variety of organs, from lung to gastro-intestinal tract [3]. The immune dysregulation characteristic of severe COVID-19 infection may be initiated by “pyroptosis”, a particularly pro-inflammatory form of apoptosis initially described in macrophages [4], with rapid viral replication leading to massive release of inflammatory mediators. One of the most consistent findings is that of a raised D-dimer. Although many inflammatory processes can influence D-dimer levels, it almost certainly reflects, to some extent, intra-vascular thrombosis in patients with COVID-19 [5, 6]. In the early studies emerging from China, an elevated D-dimer (>1000 ng·mL−1) at admission was associated with increased risk of in-hospital death [7]. An elevated D-dimer continues to be one of the most consistent markers of poor outcome [8].
Hypothesis of the origin of Covid-19-associated pulmonary emboli and lung microcirculatory thrombotic disease: Interaction of inflammation and coagulation. When coronavirus 19 infects cells expressing the surface receptors angiotensin-converting enzyme 2 (ACE2), active replication and release of the virus may cause the host cell to undergo pyroptosis (pro-inflammatory apoptosis) and release damage-associated molecular patterns (DAMPs), activating oxidant stress, and generating pro-inflammatory cytokine and chemokine release from nearby epithelial cells, endothelial cells and alveolar macrophages. These proteins in turn attract inflammatory cells to the site of infection, promoting a pro-inflammatory feedback loop. Tissue factor, usually hidden on the subendothelium, is upregulated on platelets, leucocytes and EC during inflammation, leading to activation of both the extrinsic and intrinsic coagulation pathways to make thrombin. Complement activation is also relevant. Thrombin binds to protease-activated receptors (e.g. PAR-1) to promote the formation of fibrin from fibrinogen, the activation of platelets and subsequent clot stabilisation, also propagating further inflammation. Natural anticoagulants and fibrinolytics may also be reduced in Covid 19 infection. Occluded small pulmonary blood vessels are likely to contain fibrin, platelets and coagulation factors, as well as neutrophils that become trapped in “NETS” as they pass through the lung. Ongoing inflammation provides a positive feedback loop. Additional procoagulant stimuli include lung hypoxia, for example via upregulation of PAI-1 through suppression of fibrinolysis. In this prothrombotic pneumonitis or ARDS, whether similar mechanisms promote both microthrombosis as well as larger vessel pulmonary embolic disease is not known. Abbreviations: ACE2 angiotensin receptor type 2, EC endothelial cell, ARDS acute respiratory distress syndrome, NETs neutrophil extracellular traps, PAR proteinase-activated receptor, PAI plasminogen activator inhibitor.
Full paper attached as PDF