AstraZeneca, J&J blood clot scare: What do we know about treatment, causal link with Covid-19 shots

One common link between the vaccines developed by AstraZeneca and Johnson & Johnson is that both are built with adenoviruses, a viral vector based on a weakened version of a common cold virus.

The United States has paused the use of Johnson & Johnson’s vaccine against the coronavirus disease (Covid-19) after six recipients experienced a rare and severe type of blood clot. The US Food and Drug Administration (FDA) on Tuesday said that the vaccinated individuals experienced cerebral venous sinus thrombosis (CVST) along with low levels of blood platelets.

Covid-19 vaccines of AstraZeneca and Johnson & Johnson. (Bloomberg)

This comes a week after the United Kingdom suspended the use of AstraZeneca’s Covid-19 vaccine for adults under 30s over similar concerns. A scientific review by the Medicines and Healthcare Products Regulatory Agency (MHRA) concluded that the evidence of a link between the events of blood clots and AstraZeneca’s vaccine was stronger but more work is still needed.

“No effective medicine or vaccine is without risk. We continually monitor safety during widespread use of any vaccine. This is to ensure vaccines are performing as expected, to identify any new side effects that may arise, and to ensure the benefits continue to outweigh the risks,” Dr June Raine, MHRA chief executive, said at a briefing.

One common link between the vaccines developed by AstraZeneca and Johnson & Johnson is that both are built with adenoviruses, a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus. Two teams of researchers have speculated about a possible mechanism behind the casual link in their papers published in the New England Journal of Medicine.

Both teams suggest that the development of serious blood clots along with falling levels of blood platelets is an immune response that resembles a rare reaction, called heparin induced thrombocytopenia (HIT), to the drug heparin, an anticoagulant. The first research paper described 11 blood clot cases in Austria and Germany, of which nine of them women, with a median age of 36 years.

All 11 patients tested positive for antibodies against platelet factor 4 (PF4), which are also triggered by heparin induced thrombocytopenia. However, none of the patients had received heparin before their symptoms. “Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or antibodies induced by the vaccine that cross-react with PF4 and platelets requires further study,” the researchers wrote.

In the second study, researchers in Norway described a similar pattern in five healthcare workers after receiving the first dose of AstraZeneca’s Covid-19 vaccine. Four of the patients had a major cerebral haemorrhage and three died. All of them had high levels of PF4 antibodies with no previous exposure to heparin.

Both sets of researchers have suggested treatment with intravenous immune globulin and non-heparin blood thinners. The National Health Service (NHS) of the UK has also authorised the use of intravenous immunoglobulin, which is in short supply according to UK media reports, to treat such cases.

However, Peter English, former editor of Vaccines in Practice, said that these papers do not tackle causality since the small sample size do not have the statistical power to prove causality.

“They may turn out to be useful...for clinicians treating patients with clotting disorders, and for regulators and others in deciding the safest way to proceed once causality has been confirmed—if it ever is,” The BMJ, a weekly peer-reviewed medical trade journal, quoted English as saying.