Thromboembolic events and Covid-19

Abstract

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.

Keywords: Acute respiratory distress syndrome; Anticoagulants; Covid-19; Platelets; Thromboembolic events; Thromboinflammation.

Fig. 1

Immunothrombosis mechanisms in pulmonary circulation during SARS-CoV-2 infection. A. Recruitment phase. SARS-CoV2 infects the alveolar epithelium and endothelial cells through binding to the ACE2 receptor (ACE Rc) exposed at the surface of these cells. Activation of endothelial cells by SARS-CoV-2 upregulates the externalization of Von Willebrand factor (vWF) and leukocytes' adhesion molecules (i.e. ICAM-1 (Intercellular Adhesion Molecule 1), VCAM-1 (Vascular cell adhesion protein-1), E-selectin) allowing adhesion of platelets and neutrophils. Activation of endothelial cells also triggers expression of tissue factor (TF) activating the extrinsic coagulation pathway and in turn α-thrombin generation leading to fibrin generation and platelets activation. B. Activation phase. Activated platelets interact with neutrophils leading to mutual amplification of neutrophil and platelet activation and eventually formation of Neutrophhils Extracelullar Traps (NETs) by DNA decondensation and externalization, allowing activation of the contact pathway. Thrombin generation through Tissue Factor (extrinsic) and contact pathways lead to clot formation and microvascular occlusion. Furthermore, clots are stabilized by the downregulation of endothelial antithrombotic properties. Meanwhile, cytokine release is triggered by platelets and leukocytes. C. Schematic representation of the systemic consequences of microvascular thromboinflammation.This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License;https://smart.servier.com.