CDC, FDA recommend pausing rollout of J&J vaccine over six blood clot cases
Federal health officials recommended Tuesday that the U.S. “pause” the rollout of Johnson & Johnson’s COVID-19 vaccine so experts can review six reported cases of a rare but severe type of blood clot in people who have received the vaccine.
The six cases of cerebral venous sinus thrombosis (CVST) were seen in combination with thrombocytopenia, or low levels of blood platelets, the CDC and FDA said. The six cases occurred out of 6.8 million doses of the vaccine that were administered as of April 12.
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One person died and another is in critical condition, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. All six cases occurred in women aged between 18 and 48 years who experienced symptoms 6 to 13 days after they were vaccinated, the CDC and FDA said.
The agencies said they recommended the pause “out of an abundance of caution … in part, to ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot.”
“Usually, an anticoagulant drug called heparin is used to treat blood clots. In this setting, administration of heparin may be dangerous, and alternative treatments need to be given,” the CDC and FDA said.
Marks said treatment should be given only by providers who are experienced in treating blood clots.
“Health care providers who see people presenting with either a low blood platelet count or blood clot should establish whether the patient has been recently vaccinated,” Marks said during a press briefing.
CDC Principal Deputy Director Anne Schuchat, MD, said there is no evidence of similar cases occurring among people who have received either of the other two vaccines authorized for use in the U.S. — the vaccines manufactured by Pfizer-BioNTech and Moderna — and that people with appointments to receive those vaccines should keep them.
She said people with appointments for the Johnson & Johnson shot would be contacted to reschedule their appointment to receive one of the other available vaccines, but it “may be a little bumpy."
People also may continue with their plans to receive the Johnson & Johnson vaccine despite the recommended pause, Marks said.
“This is a recommendation, not a mandate,” he said. “If an individual health care provider has a conversation with an individual patient and they determine that the benefit-risk for that individual patient is appropriate, we’re not going to stop that provider from administering the vaccine because it could be … beneficial to that individual in the large majority of cases.”
The CDC scheduled a meeting of its Advisory Committee on Immunization Practices on Wednesday “to further review these cases and assess their potential significance.” The FDA also will investigate the cases.
In a statement, Johnson & Johnson said it was reviewing the cases with European health authorities and has delayed the rollout of the vaccine in Europe.
“We have been working closely with medical experts and health authorities, and we strongly support the open communication of this information to health care professionals and the public,” the company said.
The Johnson & Johnson vaccine was authorized for emergency use by the FDA in February after clinical trials demonstrated it was safe and effective. It is the only authorized COVID-19 shot that is given in one dose instead of two.
Acting FDA commissioner Janet Woodcock, MD, said there are “too few cases” to single out any particular subgroup as being at higher risk for CVST after getting the Johnson & Johnson vaccine. Marks said the cases can be explained as a rare immune response to the vaccine that “leads to activation of the platelets and these extremely rare blood clots.”
Although no definitive cause has been established, Marks said the cases are similar to a series of reported blood clots in Europe that have been linked to AstraZeneca’s COVID-19 vaccine, which led European regulators to recommend that “unusual blood clots with low blood platelets” be listed as a “very rare side effect” of that vaccine.
Both vaccines use an adenovirus — the Johnson & Johnson vaccine uses a human adenovirus, and AstraZeneca’s vaccine uses a chimpanzee adenovirus vector. Marks said scientists would look for evidence that other adenovirus vaccines have caused similar issues.
The background rate of CVST is between 2 and 14 per 1 million people, Marks said, “but that’s in the setting of a normal platelet count.”
“The real thing that is so notable here is not just CVST or the thrombocytopenia … it’s [that they are] occurring together that makes a pattern very, very similar to what was seen in Europe” with the AstraZeneca vaccine, he said. “We have to take the time to make sure we understand this complication and we address it properly.”
The CDC and FDA said people who have received the Johnson & Johnson vaccine “who develop severe headache, abdominal pain, leg pain or shortness of breath within 3 weeks after vaccination should contact their health care provider.” They said providers should report adverse events to the Vaccine Adverse Event Reporting System.
“It’s possible we will learn of more cases. Hopefully, it’s just going to be a few,” Marks said.
The pause raised questions about the Biden administration’s goal of administering 200 million doses of COVID-19 vaccine in his first 100 days in office. Among the approximately 189 million doses of vaccine that have been administered in the U.S. so far, around 6.9 million have been the Johnson & Johnson shot.
“This temporary pause is hopefully not going to have a large adverse effect on making those goals in a timely manner, if at all,” Marks said.
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What we’re debating is an extremely rare side effect, if it is proven to be linked to the vaccine. This is less than one in 1 million, and certainly less than the risk for blood clots from getting COVID-19 itself. It appears that this may be related to a similar condition seen with the AstraZeneca vaccine and may point to something relating to adenovirus vectors, which are used in both vaccines (and also Russia’s Sputnik V and China’s CanSinoBio COVID-19 vaccines, and Johnson & Johnson’s Ebola vaccine). This vector may, in certain individuals, generate antibodies that interfere with platelet function and produce a condition similar to heparin-induced thrombocytopenia, which is diagnosable and treatable. However, it remains the case that the risk-benefit ratio strongly favors this (and the AstraZeneca) vaccine and I worry that these decisions are going to cause a litany of cancellations for the Johnson & Johnson vaccine and a relegating of it to the second tier (when regulators ultimately say that the risk-benefit ratio strongly favors the vaccine and lift the federal pause). This action will likely add to vaccine hesitancy and will do irreparable harm to the vaccine rollout and will bleed into the other vaccines as well. I fear this risk-averse stance will likely cost lives and delay control of the pandemic.
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This was a decision made out of an abundance of caution — even though this is a very rare complication, those affected (from what we know) were all reproductive-age women who experienced the event quite soon after vaccination. This, coupled with the potential mechanism that could involve anti-platelet antibodies, deserves further exploration. We don’t know enough yet to say whether this hold will be permanent. For example, were these women also on hormonal contraception, or smokers, or hypertensive — all things that independently increase the risk of thrombotic events? We urgently need a single-dose vaccine to combat the resurgence of SARS-CoV-2, so losing this vaccine would be a tough blow.
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I think we’re still learning about this. There have been only six cases of blood clots that have been reported out of 6.85 million people who have received the Johnson & Johnson vaccine. It’s an extraordinarily rare finding. They’re doing this to show their commitment to transparency, and they want to further investigate these findings — it shows that the system is working. Part of the reason for this is that for this particular type of blood clot, these patients had low platelet counts, and so they can’t be treated with heparin like they normally would. They want to better understand what’s going on, and they want to have a chance for the ACIP to publicly review the data.
The FDA wants to transparently evaluate the information, and I hope that people will see this as a good thing. They need to look at this as the regulatory agency working as it should, because they’re doing what they said they were going to do. I think that’s a really important takeaway message here — they’re being transparent, which is reassuring.