Update on AstraZeneca and blood clots

The Australian Technical Advisory Group on Immunisation (ATAGI) – the group of experts that advises the government on vaccines and vaccine policy – has released a statement on the suitability of COVID-19 vaccination in people with a history of clotting conditions. 

The announcement came after researchers from the University of Greifswald and international collaborators claimed to have found the possible link between the AstraZeneca vaccine and the unusual cases of blood clotting recently reported in Europe.

ATAGI recommended deferring the COVID-19 vaccine for people who have a history of specific rare blood-clotting disorders. However, they wrote, there is no increase in the rates of general thromboembolic conditions after vaccination over expected rates in the population.

Concerns about the AstraZeneca vaccine were raised when cases of cerebral venous sinus thrombosis (blood clots that form in the brain’s venous sinuses) associated with thrombocytopenia (low platelet count) were recorded in Europe last week.

The German-led research group discovered that the AstraZeneca jab might lead to the formation of antibodies against platelet antigens as part of the inflammatory reaction and immune stimulation. Those antibodies destroy the platelets. But at the same time, they induce a massive platelet activation that causes severe thrombosis. 

“Even though you’ve got a low platelet count, which is normally associated with bleeding, the patient gets severe and aggressive thrombosis,” explains Professor Paul Monagle, a haematologist at the University of Melbourne.

This phenomenon is sometimes observed in people who take heparin – a blood thinner – to control blood clotting. “Normally, heparin-induced thrombocytopenia occurs when patients are exposed to heparin,” says Monagle. He says that about 5% of adults on heparin develop antibodies against the platelet factor 4 (PF4): a protein on the platelet’s surface.

The researchers investigated 13 cases of cerebral vein thrombosis that occurred 4–16 days after vaccination with the AstraZeneca vaccine in 12 women and one man, aged between 20 and 63. None of them was taking heparin or other anticoagulants.

Given the immunological genesis of this “vaccine-induced prothrombotic immune thrombocytopenia” (VIPIT), the researchers suggested that patients with a history of thrombosis might not be at increased risk of suffering this rare vaccine complication.

Although the latest data indicate that the condition may be less rare than previously thought, the incidence remains at about one case every 100,000–200,000 doses. Rare enough not to be caught in clinical trials, which included a total of about 40,000 participants.

To put things into perspective, for a woman on the contraceptive pill, the rate for getting clots is about 70–100 per 100,000 for one year, and pregnant women are five times more likely to experience a blood clot compared with women who are not pregnant. Both are widely accepted risks.

Monagle says that right now, there is no way to know who’s at higher risk of developing such a rare vaccine side-effect. The fact that most cases have been recorded in young women might reflect vaccination rollout strategies, he says. Most countries have started vaccinating healthcare workers who are predominantly women under 60. 

“There’s no information from the German or other European cases to say that any one group is at higher risk than the other,” says Monagle, but he backs the ATAGI decision in being prudent until more information is available.

In the meantime, screen tests are available if the typical post-vaccine symptoms – joint pain, muscle pain and headache – persist for more than three days after the jab.

Because these vaccine-associated complications closely resemble heparin-induced thrombocytopenia, the researchers suggested that a similar therapy could be highly effective. Treatment would include intravenous immunoglobulin and an anticoagulant alternative to heparin.

“This looks like a rare complication of a vaccine,” says Monagle. “It’s nonetheless essential to make people aware of it and to manage it appropriately. But we have to remember that we’ve never as a planet embarked on such a widespread vaccination campaign across the whole adult population in such a short period of time.

“Given the impact of COVID-19 infection, being vaccinated is still the appropriate choice.”