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

Abstract

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.

Ofeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic

“…Furthermore, colchicine inhibits neutrophil-platelet aggregation and increases the levels of protein C [86], highlighting its anti-thrombotic properties [79]. Such favorable anti-thrombotic attributes of colchicine are of exceptional interest, particularly when an increasing body of evidence reports postvaccination cases of serious thromboembolic complications, such as vaccine-associated thrombocytopenia and thrombosis [87,88].…”

Novel Classification of Thrombotic Disorders Based on Molecular Hemostasis and Thrombogenesis Producing Primary and Secondary Phenotypes of Thrombosis

“…Now it is obvious that “thrombosis” is a non-specific generic term representing “blood clot(s)” without defining its origin, pathogenesis, character, pathology and/or clinical expression of dysfunction of the organ or tissue. This term provides an insufficient description in applying to clinical practice and educational system for the diagnosis and treatment [ 10 , 11 ]. Further, thrombosis has been improperly thought to be blood clot(s) caused by risk factors such as old age, affluent economic status, immobilization, prolonged high altitude flying, drug, pregnancy, and associated diseases such as diabetes, infection, autoimmune disease, cancer and sepsis, thrombophilia, and even earthquake.…”

“…Sometimes other “thrombosis” phenotypes occurring COVID-19 infection or its vaccination have included not only microthrombosis and macrothrombosis, but also other descriptive terms such as CVST [ 15 , 16 ], SVT [ 17 ], SPG [ 18 ], acrocyanosis [ 19 ], COVID toes [ 20 ] and many others. These are neither microthrombosis such as ARDS nor common macrothrombosis seen in distal DVT in their thrombotic character, but are the manifestations of combined micro-macrothrombosis resulting from the unifying mechanism of two different origins of blood clots which are the microthrombi strings from sepsis and the fibrin meshes from in-hospital vascular injury [ 10 , 11 ]. Their pathogenesis will be examined later.…”

Uveitis after COVID-19 Vaccination

“…The vaccines reduced the morbidity and mortality rates of the disease [ 3 ]. However, systemic side effects, such as thrombosis, have been reported [ 4 ]. Herein, we report a case of acute uveitis following COVID-19 vaccination.…”