Lessons from vaccine-induced immune thrombotic thrombocytopenia

Abstract

Adenoviral vector vaccines are effective against SARS-CoV-2 but have been associated with a rare side effect termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we discuss our understanding of how vaccine-induced antibodies to platelet factor 4 (PF4) form immune complexes that activate platelets and trigger the thrombotic events seen in VITT.

Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs

“…Immune thrombocytopenic purpura (ITP) has been associated with several vaccinations, including measles, mumps, rubella (MMR), hepatitis A, varicella, diphtheria, tetanus, pertussis (DPT), oral polio and influenza ( Perricone et al, 2014 ). While there is broad awareness that the adenovirus DNA-based vaccines can cause vaccine-induced immune thrombotic thrombocytopenia (VITT) ( Kelton et al, 2021 ), the mRNA vaccines are not without risk to VITT, as case studies have been published documenting such occurrences, including life threatening and fatal cerebral venous sinus thrombosis ( Lee et al, 2021 ; Akiyama et al, 2021 ; Atoui et al, 2022 ; Zakaria et al, 2021 ). The mechanism is believed to involve VITT antibodies binding to platelet factor 4 (PF4) and forming immune complexes that induce platelet activation.…”

COVID-19 microthrombosis: unusually large VWF multimers are a platform for activation of the alternative complement pathway under cytokine storm

“…Further, recent studies on SARS-CoV-2 vaccine-induced thrombotic thrombocytopenia have focused on its association with PF4, ADAMTS13 and complement activation. In particular, autoantibodies against PF4 resulting in increased stability of UL-VWFMs have been implicated in vaccine-induced thrombosis (VITT), although a possible role of the alternative complement pathway in VITT has not been characterized [ 77 , 78 ].…”

“…Indeed, these patients sometimes have a variety of autoimmune complications, such as immune thrombocytopenia (ITP) [ 72 ], Guillain–Barré syndrome [ 73 ], antiphospholipid syndrome (APS) [ 74 ], immune TTP [ 75 ], and more recently anti-factor H associated aHUS [ 76 ]. However, anti-PF4 antibody [ 77 , 78 ] rarely appears after SARS-CoV-2 vaccination. Root-Bernstein [ 79 ] recently proposed as an explanation that SARS-CoV-2-associated autoimmunity may be enhanced by coexisting bacterial or viral infections, as these pathogens have primary amino acid sequence homology with many human serum proteins.…”

Innate Immune Suppression by SARS-CoV-2 mRNA Vaccinations: The role of G-quadruplexes, exosomes and microRNAs

“…Immune thrombocytopenic purpura (ITP) has been associated with several vaccinations, including measles, mumps, rubella (MMR), hepatitis A, varicella, diphtheria, tetanus, pertussis (DPT), oral polio and influenza [149]. While there is broad awareness that the adenovirus DNA-based vaccines can cause vaccineinduced immune thrombotic thrombocytopenia (VITT) [150], the mRNA vaccines are not without risk to VITT, as case studies have been published documenting such occurrences, including life threatening and fatal cerebral venous sinus thrombosis [151][152][153]. The mechanism is believed to involve VITT antibodies binding to platelet factor 4 (PF4) and forming immune complexes that induce platelet activation.…”