Erythrocyte, Platelet, Serum Ferritin, and P-Selectin Pathophysiology Implicated in Severe Hypercoagulation and Vascular Complications in COVID-19

Abstract

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.

Keywords: COVID-19; P-selectin; erythrocytes; oxygen saturation; platelets; serum ferritin.

Figure 1

(A–F) Representative fluorescent micrographs of whole-blood samples stained with PAC-1 (green fluorescence) and CD62P-PE (purple fluorescence). The last column represents an overlay of the two micrographs. (A) Representative healthy (control) platelets. (B–F) Representative fluorescent micrographs from coronavirus disease 2019 (COVID-19) patients.

Figure 2

Representative scanning electron micrographs of the erythrocytes (A) and platelet ultrastructure (B) seen in healthy individuals. Yellow arrow points to a platelet in a whole-blood smear.

Figure 3

(A–H) Representative scanning electron micrographs of the platelet ultrastructure seen in COVID-19-positive patients. Yellow arrows show some platelet membranes damage that was observed.

Figure 4

(A–D) Representative scanning electron micrographs of the interaction between the erythrocytes and platelets of COVID-19-positive patients.

Figure 5

(A–C) A continuation of the representative scanning electron micrographs of the interaction between the erythrocytes and platelets of COVID-19-positive patients. (A–C) (column on the left) shows the low magnification micrographs of the platelet-erythrocyte interactions, with the corresponding high magnification micrographs (column on the right) to show the ultra-structures of the interactions. Arrows point to the area that was focused on.

Figure 6

(A–D) Representative scanning electron micrographs of COVID-19-positive samples with spontaneous fiber-like clotlet formations in close proximity to erythrocytes in whole-blood smears, as well as occasional granular deposits (E–H) on the erythrocytes.