PreprintReviewVersion 1Preserved in Portico This version is not peer-reviewed
COVID-19 Clot: What Is It? Why in the Lungs? Extracellular Histone, “Auto-Activation” of Prothrombin, Emperipolesis, Megakaryocytes, “Self-Association” of Von Willebrand Factor and Beyond
Version 1
: Received: 20 July 2020 / Approved: 22 July 2020 / Online: 22 July 2020 (11:03:08 CEST)
How to cite:
Varatharajah, N. COVID-19 Clot: What Is It? Why in the Lungs? Extracellular Histone, “Auto-Activation” of Prothrombin, Emperipolesis, Megakaryocytes, “Self-Association” of Von Willebrand Factor and Beyond. Preprints2020, 2020070516 (doi: 10.20944/preprints202007.0516.v1).
Varatharajah, N. COVID-19 Clot: What Is It? Why in the Lungs? Extracellular Histone, “Auto-Activation” of Prothrombin, Emperipolesis, Megakaryocytes, “Self-Association” of Von Willebrand Factor and Beyond. Preprints 2020, 2020070516 (doi: 10.20944/preprints202007.0516.v1).
Cite as:
Varatharajah, N. COVID-19 Clot: What Is It? Why in the Lungs? Extracellular Histone, “Auto-Activation” of Prothrombin, Emperipolesis, Megakaryocytes, “Self-Association” of Von Willebrand Factor and Beyond. Preprints2020, 2020070516 (doi: 10.20944/preprints202007.0516.v1).
Varatharajah, N. COVID-19 Clot: What Is It? Why in the Lungs? Extracellular Histone, “Auto-Activation” of Prothrombin, Emperipolesis, Megakaryocytes, “Self-Association” of Von Willebrand Factor and Beyond. Preprints 2020, 2020070516 (doi: 10.20944/preprints202007.0516.v1).
Abstract
COVID-19 thromboembolic disease has brought all of us back to the drawing board. In COVID-19, pre-existing activated endothelium with increased Von Willebrand factor (VWF), low density lipoprotein (LDL) promoting “self-association” and “sticking” of long VWF strings to the vascular endothelial wall, suppressed ADAMTS13 cleavage of VWF, hypoxia induced upregulation and activation of VWF, fibrous network from neutrophil extracellular traps (NETs) with free DNA and histone, all appear to be initiating the thrombogenesis. Worsening complement activation, cytokine storm and resulting endothelial destruction, unregulated thrombogenesis leads to vascular occlusions and hypoxia. At this stage, the presence of abundant extracellular DNA, histone and -defensins appears worse than the SARS-CoV-2 itself. Previously observed in vitro mechanisms like histone “auto-activating” prothrombin, histone activated platelets generating thrombin without FXII, thrombin and plasmin cleaving complement C5 appears highly likely in COVID-19. Megakaryocytes are actively producing platelets in the lungs and appear to play a major role in thrombogenesis of COVID-19 raising suspicion of emperipolesis. This focused review is a compilation of my observations in relation to the pathophysiology of the intravascular environment, mainly in COVID-19 lungs. Pathophysiology based clinical trials are paramount in reducing morbidity and mortality in COVID-19.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
