Studies explore link between AstraZeneca’s COVID-19 vaccine and blood clots

Studies explore link between AstraZeneca’s COVID-19 vaccine and blood clots
While recent reports from the European regulatory agency show that Oxford-AstraZeneca COVID-19 shot may be linked to rare blood clotting events, researchers are exploring causes that might be leading to the clotting side effects in these people.

According to two latest studies published in the New England Journal of Medicine (NEJM), researchers found that people getting the vaccine had a higher level of antibodies directed against a cluster of immune-related cells that the body might form in response to the vaccine.
These clusters included platelets, which help blood to clot in presence of a cut or an injury, and the antibodies stick to the platelet-complex and form dangerous clots that can block blood flow in veins and arteries. The researchers are referring to the condition as vaccine-induced immune thrombotic thrombocytopenia.

“The important thing is that the link to this peculiar problem of post-vaccination thrombosis which was mysterious—we now have an explanation for it,” says Dr. Theodore Warkentin, professor of pathology and molecular medicine at McMaster University and a co-author of one of the papers.

The Astrazeneca vaccine relies on a modified adenovirus vector that causes cold-like symptoms in chimpanzees. The vector serves as a vehicle in delivering genes coding for the COVID-19 virus’ spike protein. However, it is not clear whether the clotting side effect, and the platelet-involved mechanism described in the studies is related to this vector platform.

“These results cast a shadow on this vaccine and now other vaccines—the Russian vaccine, and Johnson & Johnson—relying on this technology. Now all of these will be looked at with higher scrutiny, and they should be,” revealed Times.

On April 9, the EMA announced it is currently reviewing Johnson & Johnson-Janssen vaccine after four reports of clots in people vaccinated with the shot were reported, one of which was fatal.

One of the NEJM studies, conducted in Germany and Austria, included 28 people who had been vaccinated with the AstraZeneca shot and developed clots. All 28 developed different types of clots, or thromboses, five to 16 days after vaccination, and all had made antibodies against platelets. Six of the 28 died from their clotting complications. In the other study, five health care workers in Norway who were vaccinated with the AstraZeneca vaccine and developed clots seven to 10 days later, also had high levels of platelet-specific antibodies; three died.

The strange combination of blood clots can be dangerous, and potentially fatal, if they block blood flow to the brain or lungs and a counter-intuitive deficiency of platelets that promote clotting. The clots also appeared in unusual parts of the body, such as the brain and abdomen, rather than in the legs, where most deep-vein blood clots form.

A similar phenomenon is observed in some people who are treated with the blood-thinning drug heparin. Heparin is normally used to prevent clotting, but in very rare cases can trigger a syndrome called heparin-induced thrombocytopenia (HIT), which causes blood clots together with low platelet levels.

By 22 March, the EMA had assembled 86 reports of people who had experienced blood clots in the brain or abdomen within two weeks of receiving a dose of the Oxford–AstraZeneca vaccine, developed in Britain by AstraZeneca in Cambridge and the University of Oxford. Some of these cases have been confirmed to bear the hallmarks of HIT, even though these people had not received heparin.

HIT is thought to be the result of an immune reaction to complexes formed when negatively charged heparin molecules bind to a positively charged protein called platelet factor 4, which is important for clotting. The result is activation of platelets, kicking off a chain reaction.

A co-author of the Norwegian study, says that the cases of clotting among vaccinated people is rare, but worrisome. “This devastating adverse event occurs very, very seldomly,” he says. “But for me, it’s tough to see healthy people in their 30s and 40s dying [after receiving] the vaccine when they probably would have been fine with a COVID-19 infection.”

If the vaccine continues to be used, doctors should start alerting patients about the risk as well, and monitoring people for signs of clotting. The symptoms may include blurry vision, headache, weakness in their extremities, shortness of breath, chest pain, or unusual swelling in the arms and legs about five days after getting vaccinated, says Dr Warkentin.

Doctors can test pretty quickly for the presence of the abnormal antibodies, and then prescribe blood thinning treatments that don’t include heparin. The authors also revealed that two patients in their study were successfully treated with immune globulin to help reduce the tendency of the immune cells to clump together with the platelets.

About 25 million people around the world have received the vaccine, and in March, after dozens of reports of blood clots occurring mainly in younger people who received the shot, and about 18 deaths, many countries temporarily halted vaccination.

After reviewing the side effect, the European Medicines Agency (EMA) has recently acknowledged the clot risk but concluded that the benefits of vaccination in protecting against COVID-19 outweighed the risk posed by clotting. The agency also recommended that people under age 30 years be provided other vaccines if they were available.

The EMA is asking AstraZeneca to conduct a number of investigations, including laboratory studies to determine the effect of the vaccine on blood clotting, and evaluations of data from clinical trials, to try to glean any further information about risk factors.