Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

Chiara Robba,Denise Battaglini,Antonio Vena,Italo Porto,Lorenzo Ball,Iole Brunetti,Giovanni La Malfa,Paolo Pelosi,Maurizio Loconte,Roberta Della Bona,Claudia Lucia M Silva,Nicolò Patroniti,Daniele R Giacobbe,Matteo Bassetti,Alberto Valbusa,Patricia R M Rocco

doi:10.3390/jcm10010140

Abstract

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.

Highlights

The novel coronavirus, which emerged in late 2019 in Wuhan, China, is currently causing significant concern in the medical community because of its rapid global spread [1]
High levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimers have been observed in patients with COVID-19 acute respiratory distress syndrome (ARDS), and the magnitude of the activation of the inflammatory cascade seems to be strongly correlated with the severity of coagulation disorders
A position paper from the Italian Society on Thrombosis and Hemostasis (SISET) strongly reiterated that COVID-19 patients should be covered by low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux at doses indicated for the prophylaxis of venous thromboembolism (VTE) for the entire duration of the hospital stay, and for 7–14 days more after hospital discharge [58]

Summary

Introduction

The novel coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV2), which emerged in late 2019 in Wuhan, China, is currently causing significant concern in the medical community because of its rapid global spread [1]. Helms et al reported a significantly higher risk of thromboembolic complications in COVID-19 ARDS patients when compared with non-COVID-19 ARDS (18% vs 6%, odds ratio (OR) = 3.4 (95% confidence interval (CI) = 1.7–7.3), p < 0.001) [5]. High levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimers have been observed in patients with COVID-19 ARDS, and the magnitude of the activation of the inflammatory cascade seems to be strongly correlated with the severity of coagulation disorders. The risk factors, pathophysiology, and management of these complications are still poorly understood. The aim of this manuscript is to explore the pathophysiology, clinical manifestations, and treatment of coagulation disorders in patients with ARDS-related COVID-19

Pathophysiology of Coagulative Derangements in COVID-19 Patients

Coagulation Markers and Treatment Proposals

Algorithm

Findings

Conclusions