Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis

Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by “attenuated” sepsis-like syndrome, leading to the activation of inflammatory and microthrombo...

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Autores principales: Jae C. Chang, H. Bradford Hawley
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/4a8b655a6a6441c580c8e5dbad89b4a2
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spelling oai:doaj.org-article:4a8b655a6a6441c580c8e5dbad89b4a22021-11-25T18:18:14ZVaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis10.3390/medicina571111631648-91441010-660Xhttps://doaj.org/article/4a8b655a6a6441c580c8e5dbad89b4a22021-10-01T00:00:00Zhttps://www.mdpi.com/1648-9144/57/11/1163https://doaj.org/toc/1010-660Xhttps://doaj.org/toc/1648-9144Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by “attenuated” sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included “silent” immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, “consumptive” thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined “micro-macrothrombosis” composed of binary components of “microthrombi strings” from vEA-VMTD and “fibrin meshes” from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on “two-path unifying theory” of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.Jae C. ChangH. Bradford HawleyMDPI AGarticlecombined micro-macrothrombosisCOVID 19 vaccinesendotheliopathyimmune thrombocytopenic purpura-like syndromemultiorgan dysfunction syndromethrombotic thrombocytopenic purpura-like syndromeMedicine (General)R5-920ENMedicina, Vol 57, Iss 1163, p 1163 (2021)
institution DOAJ
collection DOAJ
language EN
topic combined micro-macrothrombosis
COVID 19 vaccines
endotheliopathy
immune thrombocytopenic purpura-like syndrome
multiorgan dysfunction syndrome
thrombotic thrombocytopenic purpura-like syndrome
Medicine (General)
R5-920
spellingShingle combined micro-macrothrombosis
COVID 19 vaccines
endotheliopathy
immune thrombocytopenic purpura-like syndrome
multiorgan dysfunction syndrome
thrombotic thrombocytopenic purpura-like syndrome
Medicine (General)
R5-920
Jae C. Chang
H. Bradford Hawley
Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
description Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by “attenuated” sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included “silent” immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, “consumptive” thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined “micro-macrothrombosis” composed of binary components of “microthrombi strings” from vEA-VMTD and “fibrin meshes” from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on “two-path unifying theory” of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.
format article
author Jae C. Chang
H. Bradford Hawley
author_facet Jae C. Chang
H. Bradford Hawley
author_sort Jae C. Chang
title Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
title_short Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
title_full Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
title_fullStr Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
title_full_unstemmed Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis
title_sort vaccine-associated thrombocytopenia and thrombosis: venous endotheliopathy leading to venous combined micro-macrothrombosis
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/4a8b655a6a6441c580c8e5dbad89b4a2
work_keys_str_mv AT jaecchang vaccineassociatedthrombocytopeniaandthrombosisvenousendotheliopathyleadingtovenouscombinedmicromacrothrombosis
AT hbradfordhawley vaccineassociatedthrombocytopeniaandthrombosisvenousendotheliopathyleadingtovenouscombinedmicromacrothrombosis
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