Vaccine-induced immune thrombotic thrombocytopaenia

Autoimmunity elicited by the chemokine response to adenovirus vector vaccines may underlie vaccine-induced immune thrombotic thrombocytopaenia: a hypothesis

Andrew McLean-Tooke 1 2, Michaela Lucas 1 2 3, Martyn French 4 5

Autoimmunity elicited by the chemokine response to adenovirus vector vaccines may underlie vaccine-induced immune thrombotic thrombocytopaenia: a hypothesis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517088/

Important work.

COVID‐19 (coronavirus 19) is a global pandemic causing significant morbidity and mortality across the world. As utilised for many other infectious diseases, vaccination has formed the critical component of the public health response for the prevention of severe illness and death with multiple different vaccines now approved internationally. Two vaccinations utilising modified non‐replicating adenoviral vectors (Chimpanzee ChAdOx1 in the AstraZeneca Oxford vaccine and Human Ad26.Cov2.S in the Johnson and Johnson vaccine) have been developed and licensed for clinical use. In March 2021, concerns were raised because of vaccine safety signals, suggesting an increase in unusual thrombotic events temporally associated with the AstraZeneca vaccine. Multiple groups simultaneously identified previously well patients presenting within 21 days of an AstraZeneca vaccination with an atypical combination of thrombotic events (including cerebral sinus venous sinus and splanchnic venous thromboses) and thrombocytopaenia. 1 , 2 , 3 At presentation, patients demonstrated elevated D‐dimer levels, variable degrees of usually severe thrombocytopaenia and low fibrinogen levels. Antibodies against platelet factor 4 (PF4)‐heparin complexes, previously associated with heparin‐induced thrombocytopaenia (HIT), were identified in patient serum, although none of the patients had received heparin in the days prior to development of the syndrome. Given the clinical and serological resemblance to HIT, the condition was named vaccine‐induced immune thrombotic thrombocytopaenia (VITT). 2 Subsequently, cases of thrombosis and thrombocytopaenia related to administration of the Johnson and Johnson vaccine were identified bearing a striking similarity to the VITT cases associated with AstraZeneca vaccination. 4

The exact incidence of VITT remains unknown but is reported to be between 1 case per 26 500 and 1 case per 127 300 first doses of AstraZeneca vaccine. 5 As of 18 August 2021, the Medicine and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom had received reports of 417 thrombotic events with thrombocytopaenia (149 cases of central venous sinus thrombosis and 268 cases of other thromboembolic events) related to the AstraZeneca vaccine. 6 The majority of cases (89%) occurred after the first vaccine dose with an incidence of 15.0 per million after the first dose, dropping to 1.8 per million after the second dose. These data also show different rates with age, with a higher incidence in younger patients with rates of 20.8 per million in vaccines aged 18–49 years versus 10.9 in vaccines aged > 50 years. Overall mortality is high at 17%. As of 19 August 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) had identified 112 cases of confirmed (62 cases) or probable (50 cases) VITT after 8.1 million doses with a rate estimate for VITT after first‐dose Astra Zeneca of 29 per million doses in those < 60 years and 18 per million doses in those ≥ 60 years. 7

Understanding the pathogenesis of VITT is critical if prevention and treatment strategies are to be improved, but there is currently not a clear consensus on the pathogenesis, with several mechanisms proposed (Table 1). Here, we propose a mechanism based on the role that PF4 plays in immune responses against viruses.

Continue to read here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517088/