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.
【저자키워드】 endotheliopathy, combined micro-macrothrombosis, COVID 19 vaccines, immune thrombocytopenic purpura-like syndrome, multiorgan dysfunction syndrome, thrombotic thrombocytopenic purpura-like syndrome, venous endotheliopathy-associated vascular microthrombotic disease, 【초록키워드】 Vaccine, vaccination, thrombosis, COVID-19 pandemic, Sepsis, complement, Venous Thromboembolism, Endotheliitis, Hemostasis, Immune thrombocytopenic purpura, von Willebrand factor, pathway, Complication, phenotype, Deep venous thrombosis, in vivo, inhibitor, disease, mechanism, trauma, Inflammatory cytokine, Multiorgan, association, clinical phenotype, acute respiratory distress, Anticoagulant, Inflammatory, DVT, Major, Vascular injury, Activation, Vascular, complex, syndrome, thrombotic, Combined therapy, component, purpura, organ, venous, develop, caused, pathologic, composed, form, characterized, activated, presenting, released, promoted, distal, sepsis-like syndrome, vaccine-associated side effect, 【제목키워드】 thrombocytopenia, Combined, leading,