Ever since health officials announced Canada’s first known case of rare, post-vaccination blood clots back in April, scientists have been racing to learn more about what causes the potentially deadly condition — and how to treat it.
Now, a team from McMaster University in Hamilton has published new research-backed recommendations calling on clinicians to use a combination of two treatments: anti-clotting drugs alongside high doses of an intravenous, antibody-based therapy.
The potential effectiveness was outlined in three case studies featuring some of the first Canadian patients who developed post-vaccine blood clots, which was published Wednesday in The New England Journal of Medicine.
The three patients between the ages of 63 and 72 were all given a dose of the AstraZeneca-Oxford COVID-19 vaccine, the paper states, and were later diagnosed with vaccine-induced immune thrombotic thrombocytopenia (VITT).
Two developed clotting in their legs, including one who later required amputation, and the third suffered from blocked arteries and veins inside their brain.
“What we recognized early on is that all three patients were treated with anticoagulants [or anti-clotting medication] along with intravenous immunoglobulin, or IVIG,” said Ishac Nazy, one of the researchers behind the new report and the scientific director of the McMaster Platelet Immunology Laboratory.
IVIG is a treatment made up of antibodies that can be given intravenously, and it’s long been used to help treat autoimmune conditions.
The three patients who received the treatment all survived, the paper noted.
How does IVIG work?
So how — and why — does IVIG seem to work for patients with post-vaccine blood clots?
While there’s still more research needed into why the condition happens in the first place, the study team suspects that for certain people, getting vaccinated with a viral-vector shot like AstraZeneca leads to the development of antibodies that attack a particular blood protein, which activates platelets in the bloodstream and causes them to clump together.
IVIG treatment seems to work by flooding the system with different antibodies, which “outcompete” the patient’s own supply to prevent the chain of events leading to blood clots, Nazy explained.
The team believes the therapy slows down the blood-clotting process, giving anti-clotting drugs time to work.
“This is a multi-faceted approach to try to target the clotting event from different angles,” Nazy said.
Lab work by the team found blood samples from the three patients all showed a drop in platelet activation after the treatment.
Not a ‘perfect drug’
But outside experts on blood-clotting conditions who viewed an advance copy of the paper stressed it’s just a starting point.
While the three case studies are “encouraging,” they only provide anecdotal evidence in an area that warrants far more research, said Halifax-based hematologist Dr. Sudeep Shivakumar, the interim division head and service chief for hematology at Dalhousie University’s Faculty of Medicine.
“It’s not a slam dunk,” he added, “but it does give us ideas for future studies.”
Dr. Lana Castellucci, a thrombosis physician and researcher with the Ottawa Hospital Research Institute, agrees the findings are just a jumping-off point, but says the recommendations are in line with discussions among clinicians across Canada who are navigating how to treat VITT.
Ontario’s COVID-19 Science Advisory Table, for instance, suggested both anti-clotting drugs and IVIG in its list of VITT treatment options, which formed part of the group’s interim guidance for health-care professionals back in May.
“The potential to see this as ongoing diagnosis remains, and knowing we have treatment strategies that are effective is certainly helpful,” Castellucci said.
Nazy himself acknowledged IVIG is not a “perfect drug,” and doesn’t work for every patient — noting that one of his three wound up requiring a different treatment later on, though he too eventually improved.
There have also been concerns over access and supply levels of the plasma-based treatment in recent years.
National surveillance program set up
The McMaster lab team set up a national surveillance program for VITT earlier this year and physicians around the country began sharing their clinical data, patient samples and treatment plans and progress updates.
That helped the researchers confirm VITT cases before Canadian physicians had encountered the condition, and allowed them to gauge different treatment approaches.
Months later, there are still significant unanswered questions about the mechanism behind VITT, and why it strikes certain individuals in rare circumstances.
So far, there have been at least 28 cases reported in Canada and five deaths, following the countrywide distribution of more than 2.8 million doses of the AstraZeneca vaccine.
“Is there a particular group that’s at greater risk than others?” Castellucci questioned. “Is there an age group that’s at risk? A gender more at risk — females more than males, for example?”
Guidelines allowing Canadians the choice to switch between manufacturers for each shot, and several provinces halting the use of AstraZeneca for first doses, “takes away a lot of the uncertainty” faced by many Canadians, she added.
“We know the mRNA vaccines have not seen complications like this,” Castellucci said.