Oxford vaccine and blood clots

https://www.dailymail.co.uk/news/arti...

https://www.gov.uk/government/publica...

From 4 January to 4 August

AZ vaccine administered across the UK

24.8 million first doses

23.9 million second doses

412 suspected cases of CVST (Cerebral Sinus Vein Thrombosis) have been reported across the UK

(Only 43 suspected cases were after the second dose of AZ vaccine)

Overall incidence of CVST

After first dose, 14.9 per million

After second dose, 1.8 per million

CVST is a complication of COVID-19 infection

42.8 per million

MHRA as of 11 August, there were 73 fatal cases from the 411 events

ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome

https://www.science.org/doi/10.1126/s...

Vaccines derived from chimpanzee adenovirus

As part of the largest vaccination campaign in history,

Ultra rare side effects not seen in phase 3 trials,

including thrombosis with thrombocytopenia syndrome (TTS)

Adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4),

a protein implicated in the pathogenesis of HIT.

heparin-induced thrombocytopenia

Computational simulations to demonstrate an electrostatic interaction mechanism with PF4,

which was confirmed experimentally by surface plasmon resonance.

These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses,

an important step in unravelling the mechanisms underlying TTS.

Platelet factor 4 (PF4)

https://en.wikipedia.org/wiki/Platele...

https://www.nature.com/articles/s4142...

https://www.sciencedirect.com/topics/...

This chemokine is released from activated platelets during platelet aggregation, and promotes blood coagulation

Also has a role in inflammation and wound repair

Prof Alan Parker, Cardiff University

The adenovirus has an extremely negative surface, and platelet factor four is extremely positive and the two things fit together quite well

What we have is the trigger, but there's a lot of steps that have to happen next

Recent case reports show that most patients presenting with TTS

( more than 90%) tested positive for PF4 antibodies

A ChAdOx1/PF4 complex could induce anti-PF4 autoantibodies.

In this potential mechanism, small quantities of ChAdOx1 enter the blood through minor capillary injuries

caused by the intramuscular injection, as has previously been observed

This proposal goes some way toward explaining why TTS is observed so rarely,

because it may require a series of low frequency stochastic interactions,

first between small numbers of adenovirus particles entering the blood / lymph and then monocytes and / or B cells,

which may only occur in individuals who are predisposed toward the generation of anti-PF4 antibodies.

https://www.bbc.com/news/health-59418123