WASHINGTON (BLOOMBERG) - Rare cases of clotting that have been seen with two Covid-19 vaccines have put the spotlight on an uncommon reaction that occurs when the body unleashes its immune firepower against blood platelets.
Health officials are exploring whether and how the immune reaction may occur in people who have received vaccines made by AstraZeneca Plc and Johnson & Johnson.
Concerns have risen so high that the US Centres for Disease Control and Prevention and Food and Drug Administration jointly recommended a pause in the use of the J&J vaccine on Tuesday (April 13).
The syndrome is highly unusual in that it involves increased clotting along with low levels of platelets, the blood component mainly responsible for coagulation, and has only been seen at low rates in vaccine recipients.
The pressure is on for governments that want to hasten immunising millions of people over the next few months to understand the risk and avoid panic.
"The more challenging issue is how do we make a responsible, right communication to the public," said Behnood Bikdeli, a cardiologist at Harvard Medical School and Brigham and Women's Hospital who studies clotting and Covid-19.
"We want to be transparent, but we want to make sure that we're not scaring people out of proportion. In order of magnitude, the problem is Covid."
The appearance of severe, hard-to-predict blood clotting events in two leading vaccines is a setback in the race to vaccinate as many people as possible before next winter. It raises the possibility that some of the vaccines that were being counted on to deliver worldwide supply could have significant restrictions placed upon them that could limit their use, as is already happening with AstraZeneca's vaccine in Europe.
The AstraZeneca and J&J vaccines both use an adenovirus to help the immune system identify and battle the coronavirus. Other similar vaccines, Russia's Sputnik V shot and one from China's CanoSino Biologics Inc, may also come under scrutiny.
Six women from ages 18 to 48 suffered a type of blood clot in the brain called cerebral venous sinus thrombosis after getting the J&J vaccine, health officials said on Tuesday, with one woman dead and another in critical condition. The patients all had low levels of blood platelets, a suspicious similarity to a complication that has been observed with the vaccine from AstraZeneca and the University of Oxford.
It's also similar to another rare clotting disorder that occurs in people treated with heparin. While the anticoagulant is normally used to prevent blood clots, in rare cases it will turn the immune system against a platelet protein, which leads to dangerous reduction of levels and substantial clotting.
"The CDC is doing the right thing despite the fact that this rare blood-clotting event is at a very low rate of 1 per million, vs AstraZeneca's 1 per 100,000. The US has more than enough Pfizer-BioNTech and Moderna doses to cover its adult population by July. But the rest of the world will have weigh reopening economies vs using vaccines with rare side effects," said Sam Fazeli, BI senior pharmaceuticals analyst.
Both the AstraZeneca and the J&J vaccines are "likely inducing anti-platelet antibodies," leading to activation of the platelets and cerebral blood clots in rare cases, says Peter Jay Hotez, an immunisation expert at the Baylor College of Medicine in Houston.
"Each county will need to make decisions about continuing" with using the vaccines, or deciding on restrictions on their use, he said. "This is a problem for Africa and Latin America" as those countries were heavily depending on adenovirus vaccines for their rollout.
People who have the vaccine reaction probably shouldn't receive heparin, said Jeff Weitz, a professor at McMaster University and president of the International Society on Thrombosis and Hemostasis.
Other options like Bristol-Myers Squibb Co's Eliquis or J&J's Xarelto are probably safer oral medications, he said.
The pause on the J&J vaccine will give CDC and FDA time to review the situation and make sure doctors who see the clotting syndrome know how to respond, said Peter Marks, director of the FDA's Centre for Biologics Evaluation and Research.
The events were seen between 6 and 13 days after vaccination, and were identified by FDA through a government-run vaccine adverse event reporting system, Marks said in a webinar sponsored by the American Medical Association.
"Everyone knew it could cause a hit to vaccine confidence," he said. Though the cases "could just be a statistical aberration," the health authorities sought to exercise an abundance of caution.
Safety issues have emerged with other Covid-19 vaccines that clinicians have learned to cope with, he said.
For example, after a number of cases of anaphylaxis, a severe allergic reaction, were linked to mRNA vaccines, health authorities educated doctors on treatment.
Researchers think that the blood clots may be caused by a rare autoimmune reaction against the vaccine that leads to an unusual low platelets and severe clots. Just as heparin can in rare cases sensitise the immune system against platelets, the vaccines may create a similar reaction.
The vaccine-associated blood clots are "super rare" and show up with a very unusual patterns of clotting in the head or abdomen, said Mark Crowther, a hematologist and chair of the department of medicine at McMaster.
Unlike a stroke, where arteries bringing blood into the brain are blocked, with the vaccine-associated clots, the veins draining blood from the head get blocked, said Crowther, who's also an officer of the American Society of Hematology. That's one reason why patients often report severe headaches, he said.
In two studies published on April 9 in the New England Journal of Medicine, a research team in Norway and another group in Germany and Austria found that patients who had severe clotting reactions to the AstraZeneca vaccine had antibodies to an important clotting protein called platelet factor 4.
Six of the 11 blood-clotting cases reported by the German and Austrian researchers were fatal, while three of the five people with blood clots studied by the Norwegian scientists died, according to the New England Journal of Medicine studies.
The blood-clotting disorder "is a new phenomenon with devastating effects for otherwise healthy young adults," the Norwegian researchers from Oslo University Hospital concluded.
Hints of a connection to clotting may have arisen during J&J's final tests. In a report to the FDA, J&J said that a 25-year-old male trial volunteer in its phase 3 trial had suffered blood clotting in the brain, resulting in cerebral haemorrhage. After concluding that the event was unrelated to the vaccine, J&J resumed its US trial.
Overall, there were 14 cases of clotting and bleeding events patients who received J&J's vaccine in the trial, according to a report to the FDA. There were 10 in the group that received the placebo. Events so rare that they occur once in only thousands to millions of patients are very difficult to tie to a specific cause, said Weitz, the McMaster professor.