Cytokine storm associated coagulation complications in COVID-19 patients: Pathogenesis and Management

ABSTRACT

Introduction

SARS-CoV-2, the causative agent of COVID-19, attacks the immune system causing an exaggerated and uncontrolled release of pro-inflammatory mediators (cytokine storm). Recent studies propose an active role of coagulation disorders in disease progression. This hypercoagulability has been displayed by marked increase in D-dimer in hospitalized patients.

Areas Covered

This review summarizes the pathogenesis of SARS-CoV-2 infection, generation of cytokine storm, the interdependence between inflammation and coagulation, its consequences and the possible management options for coagulation complications like venous thromboembolism (VTE), microthrombosis, disseminated intravascular coagulation (DIC), and systemic and local coagulopathy. We searched PubMed, Scopus, and Google Scholar for relevant reports using COVID-19, cytokine storm, and coagulation as keywords.

Expert Opinion

A prophylactic dose of 5000–7500 units of low molecular weight heparin (LMWH) has been recommended for hospitalized COVID-19 patients in order to prevent VTE. Treatment dose of LMWH, based on disease severity, is being contemplated for patients showing a marked rise in levels of D-dimer due to possible pulmonary thrombi. Additionally, targeting PAR-1, thrombin, coagulation factor Xa and the complement system may be potentially useful in reducing SARS-CoV-2 infection induced lung injury, microvascular thrombosis, VTE and related outcomes like DIC and multi-organ failure.

KEYWORDS:

• Coagulation
• coagulation complications management
• covid-19
• cytokine storm

Article highlights

• Coronavirus disease 2019 (COVID-19) was first detected in China in December 2019 and declared as a pandemic by WHO on 11 March 2020.

• This review summarises the pathogenesis of SARS-CoV-2 infection – mediated generation of cytokine storm, the interdependence between inflammation and coagulation, its consequences and the possible management options for coagulation complications.

• The most vital question in the progression of COVD-19 lies in determining the link between immune response and coagulation, the extremes of both of which have resulted in cytokine storm, and the clinical presentation of venous and arterial thromboembolism, respectively.

• In view of the thrombotic risk in progression of COVID-19, anti-coagulation treatment has gained importance for both, prophylactic as well as therapeutic purposes. However, the choice of anticoagulant and intensity of anticoagulation must be varied depending on the patient condition.

• Targeting PAR-1, thrombin, coagulation factor Xa and the complement system may be a potentially useful approach in reducing coagulation complications associated with COVID-19.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.