Update, Dec. 20: On Dec. 16, a committee advising the Centers for Disease Control and Prevention voted to recommend the Pfizer/BioNTech and Moderna vaccines over the J&J vaccine because of the risk of a rare but serious blood clotting disorder coupled with low platelets. The CDC endorsed the recommendation the same day. For more information, please see our guide to the J&J vaccine.
Update, May 6, 2022: On May 5, the FDA limited authorized use of the J&J vaccine to adults who either couldn’t get one of the other authorized or approved COVID-19 vaccines because of medical or access reasons, or only wanted a J&J vaccine for protection against the disease. The FDA’s decision was based on an evaluation of the rare risk of TTS and the availability of other vaccines that haven’t shown a risk for the condition. As of April 7, 2022, the CDC and FDA had confirmed 60 cases, including nine deaths, among more than 18.6 million J&J vaccines administered.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted on April 23 to resume the use of the Johnson & Johnson COVID-19 vaccine with a warning that it may cause a very rare, but dangerous blood clotting condition.
The 10 to 4 vote came 10 days after the CDC and Food and Drug Administration on April 13 recommended “a pause in the use” of the Johnson & Johnson COVID-19 vaccine “out of an abundance of caution,” due to six reports of a rare blood clot combined with low levels of blood platelets among more than 7 million J&J vaccines administered.
At the April 23 meeting, a CDC scientist presented nine additional reported cases, bringing the total confirmed cases to 15 out of nearly 8 million vaccine doses, as of April 21. Three of the 15 have died and four remain in intensive care.
We’ll take a look at these rare conditions, their frequency and the risks of COVID-19.
What do we know about the six cases, and have there been more since the pause was recommended on April 13?
The initial six cases were among 7.2 million J&J vaccines administered. They involved women, age 18 to 48, who suffered from a combination of a type of blood clot called cerebral venous sinus thrombosis, or CVST, and low levels of blood platelets, a condition known as thrombocytopenia.
The combination of blood clotting and a drop in platelets, which help form clots to stop bleeding, “makes a pattern,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in an April 13 press conference. And that pattern has similarly been reported in Europe in relatively few cases among the millions who have received the AstraZeneca vaccine.
The FDA’s revised fact sheet for health care providers administering the J&J vaccine now says the reports of adverse events in the U.S. “suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites … combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination,” noting that most cases have involved women ages 18 to 49. The warning says: “Based on currently available evidence, a causal relationship between thrombosis with thrombocytopenia and the Janssen COVID-19 Vaccine is plausible.”
Both the AstraZeneca and J&J vaccines use the same type of technology — a modified, harmless adenovirus to prompt the body to produce an immune response to SARS-CoV-2, the virus that causes COVID-19. However, J&J scientists have pointed out that there are differences in the makeup of the vaccines.
The U.S. agencies cautioned health care providers that the anticoagulant drug normally used to treat blood clots — heparin — “may be dangerous” in these cases and “alternative treatments need to be given.”
At the April 23 ACIP meeting, Dr. Tom Shimabukuro, head of the CDC’s Vaccine Safety Team, said in his presentation that there have been, as of April 21, a total of 15 confirmed cases, including three deaths. Seven of the 15 remain hospitalized, including four in intensive care, he said.
Of the 15 total cases, 13 occurred in women between the ages of 18 and 49 and two — both disclosed on April 23 — involved women between the ages of 50 and 64.
Shimabukuro called this rare clotting condition thrombosis with thrombocytopenia syndrome, or TTS.
How rare or common are these two conditions normally — the blood clots and low levels of platelets?
This type of blood clot — cerebral venous sinus thrombosis, or CVST — is rare. It occurs in the veins in the sinuses that drain blood away from the brain.
It occurs in 2 to 14 people out of 1 million each year in the general population, according to Marks.
An April 15 CDC presentation for clinicians included similar estimates of the expected risk (0.5 to 2 per 100,000 people) and said CVST occurred in about 0.5% to 1% of all strokes. The median age for patients was 37 years. The condition was three times more common in women.
The risk factors included prothrombotic conditions, meaning a tendency to develop blood clots; birth control pills; pregnancy and post-partum; cancer; infection and lumbar puncture.
The CDC said the cases following J&J vaccination were at least three times greater than the expected rate of CVST for women in the 20-50 age group. “Observed cases following Janssen COVID-19 vaccines appear to exceed expected based on background rates of CVST among women aged 20–50 years (3-fold or greater),” the presentation said, referring to Janssen Biotech Inc., a Johnson & Johnson pharmaceutical company.
But in all cases, the patients also had low levels of blood platelets.
A low level of platelets, without accompanying CVST, is more common. Dr. Robert Brodsky, director of the division of hematology and professor of medicine at Johns Hopkins Medicine, told us, “We have people in all the time with low platelets.”
But the expected rate in the general population of the combination of CVST and low levels of blood platelets is unknown, the CDC said at its April 15 presentation.
What similarities are there between these cases and heparin-induced thrombocytopenia?
These reported cases after vaccination with the J&J and AstraZeneca vaccines appear to be similar to heparin-induced thrombocytopenia, or HIT, a condition in which the body has an immune response after a patient receives the anticoagulant heparin, causing both low levels of blood platelets and blood clots. “It appears that there is overlap between the two disorders,” Dr. Mortimer Poncz, division chief of pediatric hematology at the Children’s Hospital of Philadelphia, told us.
With HIT, antibodies attach to platelet factor 4, a protein in blood platelets. Patients can be tested for those antibodies. Eleven of the 15 U.S. cases that occurred after the J&J vaccination tested positive for the HIT antibody, and antibody results weren’t available for the other cases, according to Shimabukuro’s April 23 presentation.
Brodsky said that with the reports after the J&J and AstraZeneca vaccines, the “clinical manifestations resemble” HIT. And Poncz said there are “subtle differences” that, for instance, suggest antibodies in HIT and the vaccine cases “may or may not be recognizing distinct targets on the PF4.”
In terms of how common HIT normally is, Poncz provided statistics that would only apply for hospitalized people who receive forms of the drug heparin. In that population, HIT occurs in about 1 case in every 100 for unfractionated heparin and 1 in 1,000 for low molecular weight heparin, he said. It’s more common in the elderly.
“The thrombocytopenia often is mild,” Poncz said of HIT cases, “but the thrombosis in veins more than arteries can be striking leading to limb or life lost.”
However, CVST, the type of blood clot in the six initial U.S. cases, is “rare in HIT,” he said, as well as abdomen clots. The CVST occurrence stands out in these cases after vaccination, Poncz said in an interview a week after the CDC and FDA recommended a pause.
“There are other causes of a combination of the paradox of low platelet counts (which causes bleeding) and thrombosis,” Poncz said in an email, citing an autoimmune disorder called antiphospholipid syndrome, sepsis and severe COVID-19. With severe COVID-19, “it’s more of a diffuse all over the body process going on.”
Now that health care providers know not to use heparin, how treatable is the combination of conditions?
Poncz told us that early recognition and the use of other anticoagulants is important, and there are new, effective therapeutics for some cases. But treatment is “still a significant challenge. It doesn’t eliminate the risk of limb or life loss.”
How common have these cases been among those who have received the J&J vaccine and those who have received the AstraZeneca vaccine in Europe?
In the U.S., the 15 cases of TTS represent nearly 2 in 1 million of the nearly 8 million J&J vaccines administered as of April 21. Since 13 of those cases were among women under 50, the incidence would be 7 in 1 million for women ages 18 to 49. (The CDC said nearly 1.9 million J&J vaccine doses had been administered to women in that age group as of April 21.)
Update, Dec. 20: As of Dec. 8, the CDC and FDA had confirmed 57 cases of thrombosis with thrombocytopenia syndrome, or TTS, including nine deaths, among more than 16.9 million J&J vaccines administered.
Brodsky said there has been a wide range among the countries reviewing cases of blood clots with low platelets, with the high end being 1 in 250,000 in Norway.
Most of the worldwide cases have been in women, he said, and many of them under age 50. These are “rare, very severe life-threatening complications … that tend to occur in younger women” but not exclusively, he said.
Brodsky said there was “clearly an association with the vaccine that appears to be higher than what you would expect in the general population. To put it in perspective, Germany estimates 9-fold higher than what you’d expect in the general population.” As we said above, the CDC estimated a 3-fold higher incidence than what one would expect. But it’s “still very rare,” Brodsky said.
An April 11 news report in Science said there had been at least 222 suspected cases reported in Europe after 34 million individuals had received their first dose of the AstraZeneca vaccine. That would be a rate of 6.5 per 1 million.
The European Medicines Agency’s safety committee said on April 7 that “unusual blood clots with low blood platelets should be listed as very rare side effects” of the AstraZeneca vaccine, also known as Vaxzevria vaccine. On April 20, it said “a warning about unusual blood clots with low blood platelets should be added to the product information” for the J&J vaccine, saying that the conditions were “very rare” and that the benefits of the vaccine “outweigh the risks of side effects.”
How do these rare clotting incidents compare with the risk of dying from COVID-19?
Even among the group believed to be most affected — women between the ages of 18 and 49 — there’s a greater chance of dying of COVID-19 than suffering from this very rare clotting syndrome.
Here’s what we know:
Shimabukuro, head of the CDC’s Vaccine Safety Team, said in his April 23 presentation that there were 15 reported cases of TTS in 7.98 million people who had received the J&J vaccine, as of April 21. That’s a reported rate of 1.88 cases per million doses administered.
As we said, the reported case rate is even higher for women ages of 18 and 49. According to Shimabukuro’s presentation, there were 1,866,294 doses of the J&J vaccine administered to women 18 to 49 years old and a reported case rate of 7 per million.
As for COVID-19 deaths, the CDC reports death totals by age groups and percentage of deaths by gender.
As of April 20, the CDC website had data for 437,186 deaths by age group, including 19,727 deaths for those 18 to 49. Women ages 18 to 49 represented 34.7% of the 19,727 deaths, meaning they accounted for 6,841 deaths. Using Census Bureau population estimates for 2019, we determined there were 100 COVID deaths per 1 million women ages 18 to 49.
Below is a chart of COVID-19 deaths per 1 million population by age group for both sexes.
Clearly, older people are at the highest risk of dying of COVID-19 and even among younger women the risk is higher than the rare clotting issue identified in people who have received the J&J vaccine. Still, Brodsky said the potential risk isn’t something that should be ignored. “Your benefit of a vaccine and risk of dying from COVID really change with age.”
For a 75-year-old woman who is overweight and has conditions such as diabetes and high blood pressure, “absolutely that vaccine is going to be more helpful than harmful.” For a healthy 28-year-old woman, who has a “negligible if not zero chance of dying from COVID. … I don’t know,” he said. “Especially if other vaccines are available.”
Have vaccines been linked to other bleeding disorders?
As for the other COVID-19 vaccines authorized in the U.S., there have been reports of thrombocytopenia, the low blood platelets, but not in combination with blood clots among a few recipients of the Pfizer/BioNTech and Moderna vaccines. Whether that’s “causal or coincidental” isn’t known yet, Dr. Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and a member of the FDA’s Vaccines and Related Biological Products Advisory Committee, told us.
One study that examined 20 reports of thrombocytopenia following vaccination with those shots said the “incidence … appears either less than or roughly comparable to what would be seen if the cases were coincidental following vaccination.” The study, published Feb. 19 in the American Journal of Hematology, concluded that it was “impossible at this time” to distinguish between a vaccine-induced condition and a coincidental one.
The CDC says that “women younger than 50 years old especially should be aware of the rare risk of blood clots with low platelets after vaccination” with the J&J vaccine, “and that other COVID-19 vaccines are available where this risk has not been seen.”
Offit said thrombocytopenia occurred in 1 in 25,000 to 30,000 recipients of the measles, mumps and rubella vaccine. But natural measles infection can lead to the condition, so it’s “not surprising” that a weakened, live virus vaccine would do so but more rarely, he said.
But those occurrences, Offit said, are “completely different” from the reported cases of thrombocytopenia and blood clots after the J&J vaccination.
Update, April 30: This article has been updated with information from the FDA and CDC.
Update, April 23: This article has been updated to reflect new data and information from the April 23 ACIP meeting.
Update, July 8: We added new information on the number of cases identified by the CDC and FDA.
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.