Understanding thrombosis with thrombocytopenic syndrome after COVID-19 vaccination

An overview of the clinical and diagnostic features of VITT in the UK has been presented. VITT was described as a cause of TTS, but was not synonymous with it. When cases are collected from daily clinical meetings during vaccination campaigns, a pattern of five equally weighted clinical features emerges that are used to define the likelihood that a case is VITT. , could be classified as likely, likely, and unlikely.¹⁸The initial female overrepresentation of TTS cases appeared to reflect demographics during the early rollout of adenoviral vector vaccines in the UK. 26), a second dose of the COVID-19 vaccine in 40 UK patients with probable (2) or probable (12) VITT did not lead to recurrence of VITT. That’s it.¹⁹including some subjects (n= 5) who received a second dose of Vaxzevria.

This was supported by work done by an independent research group in Germany.The latter demonstrated that anti-PF4 antibodies in TTS vaccinees were transient²⁰Detection of anti-PF4 antibodies is an important marker for VITT, but the sensitivities of available assays vary.^{twenty one}, and ELISA-based approaches can be combined with specific functional assays. Anti-PF4 antibodies associated with VITT were previously shown not to cross-react with spike proteins, indicating that VITT is specifically induced after adenoviral vector vaccination^{twenty two}Human in vivo evidence that the anti-PF4 response in VITT is neither related to the spike protein nor to SARS-CoV2 comes from data collected in a cohort of 11 patients with a history of VITT and subsequent COVID-19. obtained fromNo significant increase in anti-PF4 antibody levels was observed after recovery from COVID-19 in these patients^{twenty three}.

Since VITT occurs from day 5 post-vaccination, the anti-PF4 B-cell response appears to be a secondary immune response, inconsistent with the notion of a conventional immune response following primary antigen challenge. Recently, the molecular signature of clonotypic anti-PF4 antibodies was identified in five of her patients.It is defined as a single IgG heavy (H) chain species paired with a single lambda light (L) chain species, all L chains belonging to the same IGLV3-21*02 gene subfamily.^{twenty four}These results may reveal a shared pathway of antibody production in patients with VITT and may indicate a genetic predisposition that may underlie the syndrome.

According to one working hypothesis, the complex formed by PF4 and adenoviral vector vaccines induces platelet activation and the downstream prothrombin cascade due to potent immune activation induced with vaccination, leading to anti-PF4 pathogenic self. May lead to the formation of antibodies.^{twenty five}Adenoviral vaccine components that bind to PF4 may induce conformational changes in PF4, creating potential neoantigens involved in marginal zone B-cell activation. This latter immunobiological process needs further investigation. However, data generated by super-resolution microscopy show that vaccine components form complexes with her PF4, to which anti-PF4 antibodies obtained from VITT patients bind in vitro. . Participants reflected on the fact that anti-PF4 antibodies are found in approximately 5% of the population.^26,27but these common antibodies do not activate platelets and may have no or only marginal clinical relevance. Pathogenic platelet-activating anti-PF4 antibodies can occur independently of thrombocytopenia-induced (HIT) syndrome.²⁸HIT is a side effect of the drug heparin.

An overview of clinical cases of vaccine-associated TTS after Vaxzevria in Australia was provided.These cases in Australia have been classified according to the approach of the International Network of Special Immunization Services to characterize the risk factors and mechanisms underlying post-vaccination adverse events of special benefit.²⁹Relatedly, a case of death after a second dose of Vaxzevria in Australia appeared to be related to a shorter dosing interval than current national recommendations. Ongoing research plans and multi-omics characterization of autoantibody-producing B-cell clones in VITT were discussed among the participants.

Interestingly, the data generated by mass spectrometry showed that anti-PF4 antibodies obtained from VITT patients were either monoclonal or oligoclonal, in contrast to anti-PF4 antibodies in conventional HIT, which were always polyclonal. rice field.³⁰In addition to the dichotomous distinction of monoclonal and polyclonal humoral responses between VITT and HIT, it is important to understand the precise binding epitopes to PF4 that are shared or not shared between the two antibody responses. It was commented that there is Recent data suggest that antibody binding to uncomplexed PF4 appears to be a key feature that distinguishes VITT from HIT and spontaneous HIT cases.³¹However, the degree of specificity of this assay needs to be evaluated in larger studies. The VITT antibody can activate platelets in the presence of heparin, as in the serotonin release assay, but consistently activates PF4-treated platelets, consistent with previous findings. Therefore, it is important that he uses only PF4-treated platelets in the VITT functional test.

Participants discussed the relative merits of centralized versus decentralized laboratories for functional testing to reliably detect cases of TTS and VITT worldwide. VITT is also associated with high optical density (OD) of anti-PF4 antibodies in the PF4 polyanion ELISA (HIT ELISA), although there are exceptions and many HIT antibodies also exhibit high OD in this assay. Moreover, a small proportion of healthy individuals are positive in this ELISA (usually his OD is low). Because of the short time window for detection of anti-PF4 antibodies in serum (sometimes as early as 5 days after immunization), the most likely immunological explanation is that TTS vaccinees show an active We had a pre-existing anti-PF4 B cell clone that could be transformed into vaccination. Further research is needed on the concept of monoclonal versus polyclonal antibodies, as well as the types and characteristics of the B cell populations involved in the immune response.