Complement activation and coagulopathy - an ominous duo in COVID19

Expert Rev Hematol. 2021 Feb;14(2):155-173. doi: 10.1080/17474086.2021.1875813. Epub 2021 Jan 22.

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; D-dimer; SARS-CoV-2; complement system; disseminated intravascular coagulation.

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use
  • Biomarkers
  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / etiology*
  • Blood Coagulation Disorders / immunology
  • Blood Coagulation Disorders / physiopathology
  • Blood Coagulation Tests
  • COVID-19 / blood
  • COVID-19 / complications*
  • COVID-19 / immunology
  • COVID-19 / therapy
  • COVID-19 Serotherapy
  • China / epidemiology
  • Comorbidity
  • Complement Activation*
  • Coronavirus Infections / blood
  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / epidemiology
  • Disseminated Intravascular Coagulation / etiology
  • Disseminated Intravascular Coagulation / physiopathology
  • Ferritins / blood
  • Fibrin Fibrinogen Degradation Products / analysis
  • Forecasting
  • Humans
  • Immunization, Passive
  • Inflammation / etiology
  • Inflammation / physiopathology
  • Iron Chelating Agents / therapeutic use
  • Ischemia / blood
  • Ischemia / etiology
  • Ischemia / physiopathology
  • Mice
  • Prevalence
  • SARS-CoV-2*
  • Severe Acute Respiratory Syndrome / blood
  • Severity of Illness Index
  • Thrombophilia / drug therapy
  • Thrombophilia / etiology
  • Thrombophilia / physiopathology
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / physiopathology

Substances

  • Anticoagulants
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Iron Chelating Agents
  • fibrin fragment D
  • Ferritins