COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on "Two-Path Unifying Theory" of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy.

Vascular Health and Risk Management
Jae C Chang

Abstract

COVID-19 sepsis is characterized by acute respiratory distress syndrome (ARDS) as a consequence of pulmonary tropism of the virus and endothelial heterogeneity of the host. ARDS is a phenotype among patients with multiorgan dysfunction syndrome (MODS) due to disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. Both affect ECs and provoke endotheliopathy. Disseminated endotheliopathy activates two molecular pathways: inflammatory and microthrombotic. The former releases inflammatory cytokines from ECs, which lead to inflammation. The latter initiates endothelial exocytosis of unusually large von Willebrand factor (ULVWF) multimers and FVIII from Weibel-Palade bodies. If ADAMTS13 is insufficient, ULVWF multimers activate intravascular hemostasis of ULVWF path. In activated ULVWF path, ULVWF multimers anchored to damaged endothelial cells recruit circulating platelets and trigger microthrombogenesis. This p...Continue Reading

References

Nov 15, 1975·Clinica Chimica Acta; International Journal of Clinical Chemistry·P J Gaffney
Dec 12, 2003·Chest·William Geerts, Rita Selby
Jan 25, 2005·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Jae C Chang, Nadeem Ikhlaque
Mar 4, 2005·Journal of the Chinese Medical Association : JCMA·Thomas Kuen-Shan Jih
Aug 28, 2007·Journal of the American Academy of Dermatology·Mark D P DavisSteven Nelson
Jan 9, 2010·International Journal of Hematology·Han-Mou Tsai
Oct 16, 2010·Journal of Thrombosis and Haemostasis : JTH·H-C YehJ-F Dong
Jan 27, 2011·The Journal of Clinical Investigation·Junmei ChenJosé A López
Dec 17, 2011·Indian Journal of Anaesthesia·Jigeeshu V DivatiaSheila N Myatra
Oct 25, 2012·Blood·Karen De CeunynckKaren Vanhoorelbeke
Nov 7, 2012·Pulmonary Circulation·Michael H Kroll, Vahid Afshar-Kharghan
Apr 27, 2013·Biochimica Et Biophysica Acta·Yuval SamuniMichael Berk
Sep 10, 2013·Journal of Thrombosis and Haemostasis : JTH·M J MourikJ Eikenboom
Aug 8, 2015·Journal of Thrombosis and Thrombolysis·Amihai RottenstreichYosef Kalish
Aug 19, 2015·Critical Care : the Official Journal of the Critical Care Forum·Clémence MinetJean-François Timsit
Oct 30, 2015·Blood·Michelle A H SonneveldFrank W G Leebeek
Jan 1, 2016·American Journal of Therapeutics·Gerardo Cabanillas, Andrea Popescu-Martinez
May 14, 2016·Cardiovascular Research·Elise S EerenbergNiels van Royen
Jan 1, 2015·Case Reports in Plastic Surgery & Hand Surgery·Keisuke ShimboMitsuo Ochi
Apr 28, 2017·Clinical and Investigative Medicine. Médecine Clinique Et Experimentale·M Feroz AzfarHameed Ullah
Jun 8, 2017·PloS One·Frederik DenormeSimon F De Meyer
Sep 21, 2017·Experimental and Therapeutic Medicine·Ying ZhangZhiqiang Wang
Jan 18, 2018·Journal of Thrombosis and Haemostasis : JTH·M LeviM Singer
May 11, 2018·Free Radical Research·Giancarlo AldiniFrancesco Sergio
Aug 1, 2018·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Jae C Chang
Sep 21, 2018·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Jae C Chang
Jan 10, 2019·Hämostaseologie·Theodore E Warkentin
Aug 6, 2019·Frontiers in Neurology·Xin ChenDanhong Wu
Nov 24, 2019·Journal of Thrombosis and Haemostasis : JTH·Marijke PeetermansPeter Verhamme
Nov 30, 2019·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Jae C Chang

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Citations

Nov 12, 2021·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Kleyton S de MedeirosAna K Gonçalves

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