FDA and CDC officials recommended pausing administration of the Johnson & Johnson COVID-19 vaccine “out of an abundance of caution,” and mainly for the benefit of healthcare providers to diagnose, treat, and report severe adverse events, the agencies said on Tuesday.
Six cases of cerebral venous sinus thrombosis (CVST) combined with thrombocytopenia were reported in the U.S., all among women ages 18-48, and all within 6-13 days, with a median of 9 days following vaccination with the Johnson & Johnson vaccine, the agencies reported in a statement.
With approximately 6.8 million doses administered in the U.S., it suggests a one-in-a-million risk. Johnson & Johnson said it was halting the product’s distribution in Europe, reportedly taking officials there by surprise.
Asked at a media briefing whether pausing administration of the vaccine was an “overreaction,” Acting FDA Commissioner Janet Woodcock, MD, said the goal was to provide “time for the healthcare community to learn what they needed about how to diagnose, treat, and report” these events.
FDA’s director for the Center for Biologics Evaluation and Research, Peter Marks, MD, PhD, noted that the condition involves a rare type of blood clots that would not be treated with heparin or related anticoagulants.
“The issue with these types of blood clots is if one administered standard treatment, one can actually cause tremendous harm or the outcome can be fatal,” he said. “One needs to make sure providers are aware if they see people with low blood platelets or blood clots, to inquire about recent vaccination and act accordingly.”
The background rate of CVST is 2-14 per million in the setting of a normal platelet count, but it is the presence of thrombocytopenia along with the abnormal clotting that makes a “pattern.” Symptoms of CVST also include severe headache, abdominal pain, leg pain, and shortness of breath.
While headache is also a common post-vaccination symptom, Marks noted key differences between the two symptoms. Headaches associated with the flu-like symptoms of vaccination tend to resolve in a few days, whereas symptoms of this rare event could present more than a week later, and would be closer to a patient presenting to the emergency department with severe headache.
None of these rare events have been observed more than 3 weeks following vaccination.
Marks also said that while this pause is recommended, this does not preclude healthcare providers from providing the Johnson & Johnson COVID-19 vaccine to their patients if they determine the benefits outweigh the risks for vaccination.
“We’re not going to stop a provider from administering a vaccine,” he added. “The benefit/risk will be beneficial overall to that individual in a large majority of cases.”
Marks said that while they don’t have a “definitive cause” for the adverse reactions, data from AstraZeneca, which reported similar issues in Europe, it is likely a “similar mechanism” with the Johnson & Johnson vaccine. Recent research has pinpointed an autoantibody against platelet factor 4 as the trigger for the reaction.
“The immune response occurs rarely after some people receive the vaccine, and that immune response leads to the activation of platelets and extremely rare blood clots,” he said.
However, Marks stopped short of calling it a “class effect,” meaning it was related to the viral vector vaccine itself. He said he wasn’t ready to make a “broad statement yet,” but “obviously it’s from the same general class of viral vectors.”
Both the AstraZeneca and Johnson & Johnson vaccines use adenovirus vectors to deliver genetic code for SARS-CoV-2 antigens. European officials last month put the rate of CVST with the former product at about 5 per million doses. Russia’s Sputnik V vaccine also uses adenovirus vectors, with different ones for the first and second doses. Although CVST has not been confirmed to occur with that product, a recent report suggests a possibility.
The only other adenovirus-vector vaccines authorized for distribution are for Ebola infection, which have not been given in numbers great enough to see clotting episodes if the true rate is in the single digits per million.
There were no similar events reported following administration of the Pfizer or Moderna vaccines, officials added.
Little is known about the details behind the U.S. cases. Woodcock said there was one death in the U.S. and one patient in critical condition. All cases were in women of reproductive age, but Marks said it was not clear there was any association with hormonal contraception, which also carries a small thrombosis risk. None of the cases appeared to have preexisting conditions or risk factors for this type of adverse event.
The American College of Obstetricians and Gynecologists (ACOG) noted there is no “clear phenotype” for women who may experience this complication.
“Until there is a better understanding of the frequency and impact of this finding, it will be important to encourage pregnant and postpartum women who wish to be vaccinated to receive the mRNA vaccines: Pfizer or Moderna,” said Christopher Zahn, MD, vice president for practice activities at ACOG, in a statement.
“If venous thrombosis is noted in the setting of thrombocytopenia, treatment includes intravenous immunoglobulin and other supportive care,” Zahn added.
CDC Deputy Director Anne Schuchat, MD, said the agency’s Advisory Committee on Immunization Practices will meet Wednesday to “review details on cases” and “risk/benefits and possible subsets of populations in a different category.”
Last Updated April 13, 2021