Everything We Know (So Far) About Blood Clots and the Johnson & Johnson Covid-19 Vaccine
It’s too soon to know what specifically caused the blood clots — that’s the biggest reason the vaccine administration was paused [I.e., we want to find out how much bigger this could turn out to be than what we report below?]
Image by Mecder
The CDC and FDA jointly recommended pausing administration of the Johnson & Johnson Covid-19 vaccine Tuesday April 13, sending a lot of people into a tailspin of questions about what the suspension means and whether the vaccine is safe. Here’s an explainer that answers as many of those questions as carefully as is currently possible — no doubt more answers will come every day.
What happened?
On April 13, the FDA and CDC jointly announced a recommendation that administration of the Johnson & Johnson Covid-19 vaccine pause to allow investigation of a possible safety concern. Out of 6.8 million doses of the vaccine given so far in the U.S., six people experienced
1. a rare [is this word somehow to modify the 6 or the 6.8 million, or what?] blood clot in the brain along with
2. a condition where the blood stops clotting effectively.
(That sounds contradictory, but we’ll get to that in a bit.) One person with this blood clot died.
It’s worth noting that the nationwide administration of a highly effective vaccine has been halted in the midst of a deadly pandemic after a single death so that authorities can investigate that death and the five non-fatal cases of blood clots. That is not to minimize the seriousness of a death occurring after a vaccination. Rather, this incident illustrates the effectiveness of the U.S. (and global) vaccine safety surveillance systems.
“The pause is a sign that the surveillance and monitoring of these events is working the way it should,” said Shikha Jain, MD, an assistant professor of medicine in the Division of Hematology and Oncology at the University of Illinois Cancer Center in Chicago.
More than 6,800 people have died from Covid-19 in the past seven days. A single death possibly related to a vaccine has interrupted use of that vaccine until we can learn more. Given the rarity of these reports — one in 1.1 million — health authorities found a needle in a haystack and immediately shut down the farm until they could learn where it came from. That’s what a highly functioning vaccine safety surveillance system looks like, and it’s how we know that the FDA and CDC take vaccine safety very, very seriously. [These3 paragraphs with 205 words are laughable. –FNC]
What condition did these people have?
1. All six individuals had a very serious condition called cerebral venous sinus thrombosis (CVST). A CVST occurs when blood clots develop in veins in the brain and create a blockage.
2. The individuals, all women between ages 18 and 48, also had a condition called thrombocytopenia. This is a condition where the body’s platelets levels drop. Platelets are the cells that help your blood clot.
What do I need to know if I recently received the Johnson & Johnson Covid-19 vaccine?
First, don’t panic. This condition is extremely rare and has not been definitively linked to the vaccine yet, said Zachary E. Rubin, MD, a pediatric immunologist at Oak Brook Allergists in northern Illinois.
But do pay attention to how you’re feeling.
“If they’ve recently gotten J&J vaccine, it’s time to listen to their body and take seriously any symptoms that they’re having, and figure out how to communicate with their primary care provider,” said Dr. Christian Ramers, MD, of Family Health Centers of San Diego. The headache, fever, chills, and aches that can occur from the vaccine show up within 12–48 hours after receiving it. But the symptoms of a possible blood clot don’t show up until one to two weeks later. “These are more concerning and unusual symptoms,” he said.
They include:
· Severe headache
· Shortness of breath
· Bleeding symptoms
· Double or blurry vision
· Numbness or weakness of one side of the body
· Inability to speak or understand words
· Severe abdominal pain or leg pain
If you experience these symptoms, contact your primary care physician or, if you don’t have one, a local clinic or emergency department. Keep in mind, we aren’t talking about a garden-variety headache here.
“People commonly complain of headaches after any vaccine. This may make people anxious that they are experiencing a blood clot,” Rubin said. “However, the headache should be severe and unrelenting.”
Can you treat this condition?
Yes, CVST [#1, above] is treatable, and early treatment can prevent death, but it’s not treated the same way most blood clots are treated. To treat most blood clots, people receive heparin, a liquid blood thinner given through an IV. (It’s the most common clear liquid in IV bags given to patients at the hospital.) With CVST, the authorities are explicitly advising AGAINST heparin, which could make the condition worse. We’ll get to the reason why in a bit, but the most important thing to know is that doctors should NOT treat CVST after a Johnson & Johnson vaccine the way they would treat another type of blood clot.
Can you treat this condition?
[#2, above. See Thrombocytopenia below.]
If it’s only a one-in-a-million risk, why did they pause the vaccine roll-out?
There are several reasons to call a time-out:
· Investigate these cases to see if they are connected to the vaccine or not
· Find out if there are other cases not yet identified
· Make sure people are aware of the symptoms so they can seek medical care if they experience symptoms after getting the Johnson & Johnson vaccine
· Make sure doctors know how to treat the condition, including not using heparin (one of the usual treatments for blood clots)
· Determine the risk of this condition if it’s connected to the vaccine
· Decide whether to change any of the recommendations for who should receive the vaccine
Doesn’t Covid-19 also cause blood clots?
Yes, blood clots have been a major defining feature of Covid-19. About one out of 100–150 non-hospitalized people with Covid gets a blood clot, according to Menaka Pai, MD, an associate professor of medicine at McMaster University in Ontario and a hematologist and thrombosis medicine physician at Hamilton Health Sciences. Once hospitalized, a person’s risk of a blood clot from Covid jumps to 1 in 20. In the ICU, 1 in 5 Covid patients develop blood clots. By comparison, so far, one out of 1.1 million people who received the Johnson & Johnson vaccine developed a blood clot, and we do not yet know if the clots are related to the vaccine.
How common is CVST, the blood clot that these people experienced, in the general population?
It’s extremely rare, occurring in about one per 100,000 people. That’s about 10 times more frequent than incidents that have occurred among recipients of the Johnson & Johnson vaccine. It occurs more often in younger people and becomes less common as people grow older. In one study, only 8% of patients were older than 65. CVST tends to occur three times more often in women than in men. Women tend to be more prone to developing blood clots in general because estrogen ramps up blood clotting activity, Pai explained.
That said, knowing the rates of CVST is in the general population may not tell us much right now. “Background rates of CVST is a really hard concept to rely upon, since this is an entity that is so rare, and most commonly associated with some other condition,” Ramers said. He pointed to this graphic from Jesse O’Shea, MD, an infectious disease and internal medicine physician in Atlanta.
What could have caused the blood clots? Could the vaccine have caused them? How?
It is possible the vaccine caused these blood clots, but researchers don’t yet know if that’s what happened. It’s too soon to know what specifically caused the blood clots — that’s the biggest reason the vaccine administration was paused. But we can look to two other vaccines, the measles vaccine and the AstraZeneca Covid-19 vaccine, to learn one way this condition might occur.
What does the measles vaccine have to do with this?
Thrombocytopenia (low platelets) is a known side effect that can occur in one out of 40,000 people who receive the measles-mumps-rubella (MMR) vaccine. The condition, called immune thrombocytopenic purpura (ITP), can also occur after a measles infection. In both cases, it’s caused by an immune reaction in the body, Pai explained. The antibodies the body makes against the measles virus also target a part of a platelet. These antibodies therefore destroy some platelets, temporarily dropping platelets levels in body. Sometimes the condition ends on its own, and sometimes the person needs medication and/or a blood transfusion. Thrombocytopenia after a measles vaccine does not involve blood clots and is not usually life-threatening.
So how does the AstraZeneca vaccine come into play here?
The AstraZeneca Covid-19 vaccine has been linked to a similar but more serious condition called Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT). Notice the “prothrombotic” addition there: thrombosis means blood clot, so prothrombotic means “promoting/causing blood clots.” Since it’s brand new, a different proposed name is vaccine induced immune thrombotic thrombocytopenia (VITT), which will likely become the final name. This explainer, developed by Pai and her colleagues, explains VITT nicely, but we’ll cover the basics here.
It’s important to keep in mind that the next several paragraphs describe what’s happening with the AstraZeneca vaccine. We don’t know yet if it’s the same thing occurring with the Johnson & Johnson vaccine, but there is a good reason it could be: both vaccines use a similar “platform,” or framework, for making the vaccine. More on that in a moment.
It’s [only] been three weeks since thrombocytopenia with blood clots have been linked to the AstraZeneca vaccine. Here’s what scientists have learned in that time:
— It occurs 4–20 days after the vaccine because that’s how long it takes your immune system to develop antibodies.
— Data from the U.K. suggests this condition occurs in one out of 250,000 people who receive a dose of the vaccine. Data from the European Union suggests it occurs in one out of 125,000 people. The difference may be age: This condition appears to be more common in younger people — though that’s still not confirmed — and the U.K. dataset includes more older adults.
— The mechanism is similar to what happens after the measles vaccine with an extra crucial step: in addition to destroying platelets, the antibodies made by the body also activate platelets. It activates an antigen (something that gets the immune system’s attention) called Platelet Factor 4, or PF4. “Your body is filled with these auto-antibodies, and now your body is thrombotic,” Pai said. In other words: your body made a bunch of antibodies against the Covid virus, but it also made a bunch of antibodies that attack PF4 on platelets, destroying some and stimulating others to go a bit haywire. That’s how it’s possible for your body to have a drop in platelets levels (clotting ability) while also developing clots at the same time.
How did scientists figure that out so fast?
This happened in two ways, starting with international cooperation. “It’s a global community,” Pai said. “Researchers and doctors and hematologists are a small community and sharing information and supporting each other.” Seriously — scientists across the world are constantly sharing data in real time to learn everything they can about Covid and the vaccines and then making sure everyone else knows it too.
Second, this condition is very similar to another known condition called heparin-induced thrombocytopenia (HIT). Remember above where I said that heparin should NOT be used to treat CVST after a Johnson & Johnson vaccine? Here’s why. Heparin is usually used to thin the blood to reduce the risk of clotting during and after surgery or other situations that could increase the risk of blood clots. (It’s commonly used in hospitals because sitting still for long periods of time — such as on a hospital bed — increases the risk of blood clots.)
Sometimes, however, in people receiving heparin, “their body makes an antibody to the heparin and Platelets Factor 4 on platelets,” Pai said. “That auto-antibody destroys the platelets and switches them on, and you get these really bizarre clots. It is an immune response; your body is targeting itself.”
HIT leads to the same problems seen with VITT, which is why giving heparin to someone with blood clots after an AstraZeneca vaccine could actually worsen the condition. While it’s not certain that these six clots seen after the Johnson & Johnson vaccine are the same condition, the possibility that they could be is the reason the FDA and CDC are cautioning doctors not to use heparin.
What are the symptoms of the AstraZeneca vaccine blood clotting?
· A severe, persistent headache — it just won’t go away or lessen
· Shortness of breath
· Blurred vision
· Chest or abdominal pain
· Swelling or redness in arms or legs
· Pale color or coldness in arms or legs
· Seizures
Does the blood clot only happen in the brain?
With the condition occurring after the AstraZeneca vaccine, not necessarily. It could occur in arteries or in veins anywhere in the body.
So far, all the cases following the Johnson & Johnson vaccine have occurred in the brain. There are too few cases to know if that’s the only place it will or could occur.
How long does the risk last?
The risk of VITT after the AstraZeneca vaccine is about 21 days, the longest it’s likely to take your body to produce antibodies. If the condition being investigated by the CDC and FDA after Johnson & Johnson vaccines is the same, the risk period will be the same.
So how do you treat this low-platelets-with-blood-clotting thing?
If you have the symptoms of VITT after the AstraZeneca vaccine, the first thing a doctor will do when someone comes in with symptoms is a complete blood panel (CBC) to see if their platelets are low.
“If your platelets aren’t low, you don’t have this,” Pai said. If you do have low platelets, the doctor then draws blood to test other markers to see if your lab values match what would be expected from VITT. If it appears you have it, the doctor will give you non-heparin anticoagulants (blood thinners) and intravenous immunoglobulin (IVIG), the same treatment given for Multisystem Inflammatory Condition in Children (MIS-C) from Covid. IVIG tells your immune system to chill out and reduces inflammation. In fact, the very first use of IVIG was precisely for immune thrombocytopenic purpura (ITP), starting in 1981. You may receive steroids or some other treatments.
“Yes, it’s scary but we know how to diagnose it and we know how to treat it,” Pai said.
Will that be the treatment in people who develop blood clotting symptoms after the Johnson & Johnson vaccine? We don’t know yet because it hasn’t been determined whether it’s the same condition. Right now it’s all speculation and questions.
Why does the AstraZeneca vaccine lead to this VITT condition?
That’s an open question. “We don’t know exactly what it is about the AstraZeneca vaccine that triggers it, and we REALLY don’t know what’s going on with Johnson & Johnson,” Pai said. If what’s happening with the J&J vaccine is the same thing being seen with AstraZeneca, “then that leads to some speculation about what’s causing it,” she said.
One possibility is the common platform: Both vaccines use an adenovirus — a common cold virus modified so it can’t replicate — to carry DNA instructions for making the spike protein to cells. These vaccines work similarly to mRNA vaccines except mRNA vaccines contain mRNA instructions in a liquid fat droplet, and AstraZeneca and Johnson & Johnson vaccines contain DNA instructions in the hollowed out adenovirus.
“It is well known that adenovirus binds to platelets and causes platelet activation,” researchers wrote in the recent NEJM study on VITT. Though they don’t think a tiny amount of adenovirus exposure on its own is likely to have caused the blood clotting condition, “interactions between the vaccine and platelets or between the vaccine and PF4 could play a role,” they wrote. It’s possible, for example, that the free-floating DNA inside the adenovirus is attaching itself to PF4 and contributing to the activation. But that’s just speculation. Right now, there’s a lot we don’t know and a lot that scientists are furiously trying to find out.
Are these clots a risk with the mRNA vaccines?
Not so far, said Jain. “With the data and evidence that is out there right now, if there is a causal relationship between the vaccines and these rare clotting cases, the two vaccines that need to be looked at more closely are the AstraZeneca and Johnson & Johnson,” she said.
The lack of reports for the Moderna and Pfizer/BioNTech is great news, suggesting the culprit activating PF4 is probably not the spike protein, Pai said. That means this blood clotting condition is not something that would occur with all Covid-19 vaccines.
In fact, Ramers pointed out, data has shown no increased risk of typical blood clots from any of the vaccines.
Why didn’t we find out about these clots during clinical trials?
Clinical trials enroll tens of thousands of people so that they have a better chance of identifying rare adverse events, or side effects. But these clots have occurred at a rate of one in 1.1 million. Trials of 40,000–50,000 people simply cannot detect something this rare, if it’s linked to the vaccine.
That said, there was one case of CVST that occurred in the Johnson & Johnson phase 3 trial. The trial was paused October 11, 2020, to investigate a 25-year-old man who had a cerebral hemorrhage and transverse sinus venous thrombosis. According to an FDA briefing document on the vaccine (see page 47), the researchers determined that the event was not related to the vaccine. It’s still unclear whether that case and these other six cases are similar.
Who’s at the greatest risk for this condition? Are there any groups that should not get the Johnson & Johnson vaccine?
Slow down… that’s exactly what scientists are trying to find out. Right now, there is not enough data to tell which groups could have an increased risk of clots — if these clots are even caused by the Johnson & Johnson vaccine, something that hasn’t been shown yet.
There are certain risk factors that can increase the risk of blood clots in general:
· Having a recent surgery
· Pregnancy
· Being immobile for long periods of time
· Smoking
· Carrying a lot of extra body weight
· Family history of blood clots or clotting disorders
· Taking certain types of hormonal birth control (not all types)
However, it’s not clear if these risk factors apply to blood clots following vaccination. “Even though all of the cases in the United States were in females, there is not enough information or number of cases to determine particular risk factors for clotting at this time,” Rubin said.
Is this the same kind of blood clot that people can get if they’re taking birth control pills?
Not exactly, and we don’t know if receiving the vaccine while taking hormonal birth control increases the risk of clots — again, if the clots are related to the vaccine. The risk of blood clots with hormonal birth control containing estrogen tends to be about one out of 1,000 people. That’s not as rare as what’s being seen with the Johnson & Johnson vaccine, but it’s still extremely rare. It’s also a lot less than the risk of blood clots during pregnancy, which is about one in 300.
What’s next?
The CDC issued an official health alert to notify health care workers, public health officials, and the general public on what to look out for. On Wednesday, April 14, the CDC’s Advisory Committee on Immunization Practices is holding an emergency meeting from 1:30–4:30 pm ET to review the existing data and determine what changes, if any, should occur in recommendations for the Johnson & Johnson vaccine. Like all ACIP meetings, it is open to the public. You can find the webcast link here.
So let’s say these blood clots are caused by the Johnson & Johnson vaccine. What does that mean?
It means you have to evaluate the risks and benefits of the vaccine against the risks of catching Covid and all that comes with it, including risk of hospitalization, long-term symptoms, and death. Unfortunately, humans aren’t great at those kinds of assessments, “sort of like the kid who needs to fall out of the tree to realize that he/she needs to be careful when playing in the tree,” Ramers said. But we have to keep trying.
“We face much greater risks of death every time we get in our cars, not to mention the approximately 1% mortality risk of getting Covid or the approximately 20% risk of blood clots if admitted with Covid,” Ramers said. “This is a very hard message to convey for public health officials, but it is happening in real time in the EU. They have 222 cases of CSVT out of 34 million AstraZeneca vaccinations and have to try to convey that, yes, it seems like a real association, but also that Europe is on fire right now and the risk of dying of Covid is so much greater.”
[Ramers's " approximately 1% mortality risk of getting Covid " is wildly high, in reporting the infection fatality rate of COVID-19 without a vaccine regimen (including boosters). ]
There is a straightforward question that most people would like answered. If someone is infected with COVID-19, how likely is that person to die?
This question is simple, but surprisingly hard to answer.
Here we explain why that is. We’ll discuss the
“case fatality rate”, the
“crude mortality rate”, and the
“infection fatality rate” [what we really want to know],
and why they’re all different.
The key point is that the “case fatality rate”, the most commonly discussed measure of the risk of dying, is not the answer to the question, for two reasons. One, it relies on the number of confirmed cases, and many cases are not confirmed; and two, it relies on the total number of deaths, and with COVID-19, some people who are sick and will die soon have not yet died. These two facts mean that it is extremely difficult to make accurate estimates of the true risk of death.
[Go here for more about this https://ourworldindata.org/mortality-risk-covid .]
What we want to know isn’t the case fatality rate: it’s the infection fatality rate
Before we look at what the CFR does tell us about the mortality risk, it is helpful to see what it doesn’t.
Remember the question we asked at the beginning: if someone is infected with COVID-19, how likely is it that they will die? The answer to that question is captured by the infection fatality rate, or IFR.
The IFR is the number of deaths from a disease divided by the total number of cases. If 10 people die of the disease, and 500 actually have it, then the IFR is [10 / 500], or 2%.3,4,5,6,7
To work out the IFR, we need two numbers: the total number of cases and the total number of deaths.
However, as we explain here, the total number of cases of COVID-19 is not known. That’s partly because not everyone with COVID-19 is tested.8,9
We may be able to estimate the total number of cases and use it to calculate the IFR – and researchers do this. But the total number of cases is not known, so the IFR cannot be accurately calculated. And, despite what some media reports imply, the CFR is not the same as – or, probably, even similar to – the IFR.
[Now, we continue with Ramers's notions of risk.]
He emphasized how small a risk of one in 1 million is.
“I would still recommend — even for my 12-year-old-daughter — to receive the J&J vaccine so as to benefit from immune protection, freedom to be with her girlfriends and have sleepovers, go to soccer practice without a mask, and so on,” Ramers said. “She does far riskier things every day, and we are still seeing approximately 200–300 cases per day in San Diego County, including in children.”
Rubin tries to help patients consider risks and benefits by putting them into context with other risks:
· “The risk of blood clots postpartum is about 40–65 per 10,000 during the first 12 weeks.
· The risk of getting hit by lightning is about twice as high as the risk of getting a clot from this vaccine.
· You are much more likely to get hit by a car than get a clot from this vaccine.”
This graphic nicely shows a comparison of benefits to risks of getting the AstraZeneca vaccine. It’s not directly comparable to the Johnson & Johnson vaccine, but it gives you an idea of how the benefits build up over time, especially since the risk period for the blood clots lasts only three weeks and the clots are identifiable and treatable.
“The silver lining of all this is that the scientific community is actively surveilling and sharing information,” Pai said. “This is proof that vaccine surveillance systems work. We’re pausing to get more information, and my hope is that in the coming weeks and months we’ll be able to offer better risk estimates.”