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

COVID-19: «Американские горки» фибрина(фибриногена), D-димера, фактора фон Виллебранда, P-селектина и их взаимодействие с эндотелиальными клетками, тромбоцитами и эритроцитами
Corlia Grobler, Siphosethu Cassandra Maphumulo, Lize M. Grobbelaar, Jhade C. Bredenkamp, Gert Jacobus Laubscher, Petrus Johannes Lourens, Janami Steenkamp, Douglas B. Kell, Etheresia Pretorius
2020-07-21

COVID-19 coagulopathyD-dimerP-selectinfibrinogenvon Willebrand factor
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.
1
COVID-19 is associated with heterogeneous coagulopathies, including bleeding with thrombocytopenia and hypercoagulation with thrombosis, particularly in vulnerable patients with comorbidities.
2
Disease progression is characterized by rapidly increasing D-dimer, very high P-selectin, and eventual depletion of von Willebrand factor and fibrinogen; this pattern, especially with cytokine storm, indicates poor prognosis.
3
Early disease may feature elevated von Willebrand factor, P-selectin, and fibrinogen with normal or slightly increased D-dimer levels, representing a potential treatment window.
4
Fibrinogen, D-dimer, von Willebrand factor, and P-selectin interact with endothelial cells, platelets, and erythrocytes and reflect vascular and cellular dysfunction during disease progression.
5
Point-of-care coagulation monitoring and personalized treatment may improve COVID-19 management by adapting therapy to evolving biomarker profiles.

COVID-19-associated coagulopathy involving fibrinogen, D-dimer, von Willebrand factor and P-selectin, and their interactions with endothelial cells, platelets and erythrocytes

Disease-stage-dependent changes, depletion patterns and vascular-cell interactions of coagulation biomarkers associated with thrombotic and bleeding outcomes in COVID-19

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2020-07-21
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Corlia Grobler
Siphosethu Cassandra Maphumulo
Lize M. Grobbelaar
Jhade C. Bredenkamp
Gert Jacobus Laubscher
Petrus Johannes Lourens
Janami Steenkamp
Douglas B. Kell
Etheresia Pretorius
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