Complement activation and coagulopathy - an ominous duo in COVID19

ABSTRACT

Introduction

COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management.

Areas Covered

Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords ‘COVID-19’, ‘SARS-CoV-2’, ‘Coronavirus’, ‘Coagulopathy’, and ‘D-dimer’. Twenty-two studies were taken for weighted pooled analysis of D-dimer.

Expert opinion

A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• D-dimer
• disseminated intravascular coagulation
• complement system

Article highlights box

• Complement system acts as a doubled-edged sword, both activating the immunity against the viral pathogens and disease progressing pathways.

• The cross-talk between the complement system and the coagulation cascade in the COVID-19 patients may lead to an enhanced rate of coagulopathy.

• Coagulation abnormalities in COVID-19 show characteristics of both consumption coagulopathy and prothrombotic coagulopathy.

• Comorbidities in COVID-19 enhances with risk of coagulopathy owing to low chronic low-grade inflammation leading to complement activation and coagulopathy.

• The presentation of anomalies of coagulation pathway in COVID-19 patients appeared to differ with respect to race and geography.

• D-dimer has diagnostic and prognostic utilities in assessing the coagulation anomalies in COVID-19 patients, with population-specific variations possibly due to genetic variations.

• The pooled analysis of D-dimer demonstrated the progressive increase in D-dimer with the severity of the disease.

Additional information

Funding

This paper was not funded.