The Interplay Between Coagulation and Inflammation Pathways in COVID-19-Associated Respiratory Failure: A Narrative Revi
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REVIEW
The Interplay Between Coagulation and Inflammation Pathways in COVID-19-Associated Respiratory Failure: A Narrative Review Rajat Bhattacharyya
. Prasad Iyer . Ghee Chee Phua .
Jan Hau Lee
Received: June 30, 2020 Ó The Author(s) 2020
ABSTRACT The novel coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide socio-economic and health impact. There is increasing evidence that a combination of inflammation and hypercoagulable state are the main mechanisms of respiratory failure in these patients. This narrative review aims to summarize currently available evidence on the complex interplay of immune dysregulation, hypercoagulability, and thrombosis in the pathogenesis of respiratory failure in COVID-19 disease. In addition, we will describe the experience of anticoagulation and anti-inflammatory strategies that have been tested. Profound Digital Features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12739562. R. Bhattacharyya (&) P. Iyer Haematology-Oncology Service, Department of Paediatric Subspecialties, KK Women’s and Children’s Hospital, Singapore, Singapore e-mail: [email protected] P. Iyer G. C. Phua J. H. Lee Duke-NUS Medical School, Singapore, Singapore G. C. Phua Singapore General Hospital, Singapore, Singapore J. H. Lee Intensive Care Unit, Department of Paediatric Subspecialties, KK Women’s and Children’s Hospital, Singapore, Singapore
suppression of the adaptive and hyperactivity of innate immune systems with macrophage activation appears to be a prominent feature in this infection. Immune dysregulation together with endotheliitis and severe hypercoagulability results in thromboinflammation and microvascular thrombosis in the pulmonary vasculature leading to severe respiratory distress. Currently, some guidelines recommend the use of prophylactic low molecular weight heparin in all hospitalized patients, with intermediate dose prophylaxis in those needing intensive care, and the use of therapeutic anticoagulation in patients with proven or suspected thrombosis. Strong recommendations cannot be made until this approach is validated by trial results. To target the inflammatory cascade, low-dose dexamethasone appears to be helpful in moderate to severe cases and trials with anti-interleukin agents (e.g., tocilizumab, anakinra, siltuximab) and non-steroidal anti-inflammatory drugs are showing early promising results. Potential newer agents (e.g., Janus kinase inhibitor such as ruxolitinib, baricitinib, fedratinib) are likely to be investigated in clinical trials. Unfortunately, current trials are mostly examining these agents in isolation and there may be a significant delay before evidence-based practice can be implemented. It is plausible that a combination of anti-viral drugs together with anti-inflammatory and anti-coagulation medicines will be the most successful strategy in
Pulm Ther
managing severely COVID-19.
affected
Keywords: Anti-coagulation; inflammatory; COVID-19; dysregulation; Thrombosis
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