With more than 80 per cent of the world’s population still unprotected against COVID-19, a team of Canadian researchers has documented a successful treatment for blood clots associated with the Oxford-AstraZeneca vaccine, a crucial weapon in the global effort to combat the pandemic.
The results provide confidence that the clotting can be arrested if caught in time. However, they do not entirely eliminate the possibility of death or serious complications related to the rare condition known as vaccine-induced immune thrombotic thrombocytopenia, or VITT.
In a study published Wednesday in the New England Journal of Medicine, a team led by researchers at McMaster University in Hamilton, Ont., reported on the treatment of three Canadian patients who developed VITT. Each patient received a combined therapy consisting of antibodies delivered intravenously along with anticoagulants.
While the approach has already been used, the Canadian case series is the first to show both the effectiveness of the therapy and why it can halt the formation of blood clots following vaccination, said Ishac Nazy, scientific director of McMaster’s Platelet Immunology Laboratory and a co-author on the study.
Dr. Nazy said he and his colleagues have observed similar results in other patients, but only three were included in the study in order to hasten publication.
“We wanted to get this out as soon as possible so that doctors have the knowledge of how this is working and what to look for,” Dr. Nazy said.
Analysis of the patients showed that the antibodies they received as part of their treatment were able to crowd out a different population of “VITT antibodies” that developed in response to the vaccine. It is the VITT antibodies that form complexes that can link up with clotting factors in the blood stream and activate platelets. This tends to release more clotting factors, touching off a cascade that leads directly to VITT. The antibody therapy was shown to block that process, though it did not directly eliminate the VITT antibodies from patients.
Ted Warkentin, a McMaster researcher and hematologist who also participated in the study, said that the results provide a trove of new information about the life-saving treatment. He added that one of the patients suffered a severe stoke and another had to have part of a foot amputated as a result of VITT, demonstrating the serious consequences that can arise for some who developed the rare condition.
“It’s sobering that two of the three patients had life-altering clots,” Dr. Warkentin said.
The study also found that one of the three patients had a relapse and was switched to a different therapy.
Researchers have not yet worked out precisely what it is about the AstraZeneca vaccine – and to a lesser degree the one-dose vaccine made by Johnson & Johnson – that triggers VITT, or why it is so rare.
Since March, more than 2.2 million Canadians have received the AstraZeneca vaccine or its made-in-India counterpart, according to data from Health Canada. Of those, some 40 individuals developed signs of VITT within 3 to 34 days after vaccination. As of May 28, five of those cases have resulted in death.
This rate mirrors the approximately 1-in-50,000 chance of developing VITT observed in other countries. While the risk remains low, particularly when compared to the risks associated with COVID-19, it proved enough to turn many Canadians off the AstraZeneca vaccine when alternatives began arriving in large numbers last month. By then, the National Advisory Committee on Immunization had already designated the mRNA vaccines made by Pfizer-BioNTech and Moderna as the preferred options when available.
The question is where that leaves the rest of world, particularly countries that lack the resources to buy mRNA vaccines.
“Not every country has that luxury right now,” said Ben Chan, a physician and assistant professor with the University of Toronto’s Institute for Health Policy, Management & Evaluation.
The challenge, he added, is that lab tests that can identify VITT, MRI scans that spot blood clots and specialists that can deliver antibody therapy are also luxuries that are hard to come by in many parts of the world, especially where the AstraZeneca vaccine could be used to best effect.
“We do have to be realistic about whether low- and middle-income countries will have the resources available to quickly diagnose and treat VITT,” Dr. Chan said.
He added that one very positive development is that the rare syndrome was discovered and an effective treatment developed in a matter of weeks. “In my 31 years as a physician, I have never seen science evolve so quickly,” he said.
Paul Petrasek, a vascular surgeon and an associate professor at the University of Calgary, said that Canadian physicians now are far better informed about VITT, relative to what was known in early April when he first encountered a 63-year-old male patient with the condition.
“We were initially misled because of some of the early data coming out of Europe,” Dr. Petrasek said.
Those data suggested VITT was primarily an issue in younger women. That would turn out to be an artifact caused by the fact that front-line health care workers who were among the first to receive the AstraZeneca vaccine are dominated by that demographic group.
Dr. Petrasek added that it took two additional days to recognize what his patient was experiencing. The case is one of the three documented in the McMaster study.
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