Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Int J Mol Sci. 2020 Jul 21;21(14):5168. doi: 10.3390/ijms21145168.


Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

Keywords: COVID-19; bleeding; fibrin(ogen); thrombosis.

Publication types

  • Review

MeSH terms

  • Betacoronavirus
  • Blood Platelets / metabolism*
  • COVID-19
  • Coronavirus Infections / pathology*
  • Cytokine Release Syndrome / pathology
  • Endothelial Cells / metabolism*
  • Erythrocytes / metabolism*
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Humans
  • P-Selectin / metabolism*
  • Pandemics
  • Pneumonia, Viral / pathology*
  • Point-of-Care Systems
  • Precision Medicine / methods
  • SARS-CoV-2
  • Thrombocytopenia / pathology
  • Thrombosis / pathology
  • von Willebrand Factor / metabolism*


  • Fibrin Fibrinogen Degradation Products
  • P-Selectin
  • SELP protein, human
  • fibrin fragment D
  • von Willebrand Factor