COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Abstract

<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), 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 occurs in subjects with weak multiple risk factors and co-morbidities. 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 activity of these biomarkers are their receptors and signaling 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 still low levels of D-dimer. 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 devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.</jats:p>

Prevalence of amyloid blood clots in COVID-19 plasma

“…Strongly bound up with the coagulopathies accompanying severe COVID-19 disease is the presence of hyperferritinaemia (in cases such as the present it is a cell damage marker (28)) and a cytokine storm, (29)(30)(31)(32)(33) which usually occurs in the later phase of the disease (16). Excess iron has long been known to cause blood to clot into an anomalous form (34), later shown to be amyloid in nature (18)(19)(20)(21)(22)(23)(24).…”

Practical Recommendations for Treatment of Dental Patients with Congenital Bleeding Disorders during the Covid-19 Pandemic: A Narrative Review

“…In the literature, the possibility of thromboembolic disorders in this group of patients, a thrombotic episode in a patient with mild VWF disease [ 19 ] and the possibility of bleeding associated with SARS-CoV-2 infection [ 20 ] have all been reported. All the while there is a discussion about a possible association between complications and the level of factor VWF [ 21 , 22 ]. It has also been shown that the incidence of concomitant diseases has an impact on the severity and mortality of COVID-19 [ 11 , 12 , 13 , 14 , 15 , 16 ].…”

“…The literature suggests the possibility of thromboembolic disorders, also in patients with CBD [ 19 ]. There are known cases of bleeding related to COVID-19 infection [ 20 ] and also the influence of VWF factor level on the risk of complications is discussed [ 21 , 22 ]. The aim of this article is to give recommendations to doctors and dentists for the optimal management of patients with CBD during the SARS-CoV-2 pandemic.…”

Assessment of Fibrinogen Macromolecules Interaction with Red Blood Cells Membrane by Means of Laser Aggregometry, Flow Cytometry, and Optical Tweezers Combined with Microfluidics

“…Abnormalities in RBC aggregation also accompany cardiovascular diseases such as arterial hypertension [ 17 , 18 ], atherosclerosis [ 19 ], cardiac infarction, and ischemia [ 20 ], as well as during metabolic disorders such as diabetes mellitus [ 21 , 22 ]. During COVID-19 infection, pathological levels of fibrin and fibrinogen result in elevated membrane fragility and the pathological elasticity of erythrocytes [ 23 ]. Therefore, a complex study of the interaction between fibrinogen molecules and RBC will allow developing new approaches of the targeted treatment of hemorheological disfunctions caused by an evaluated fibrinogen-induced aggregation of RBC.…”