Last updated on September 20th, 2021 at 10:56 am
There have been extremely rare reports about blood clots being related to the JNJ and AstraZeneca COVID vaccines. Although science does not why this happens, researchers continue to explore why these COVID-19 vaccines might be linked to blood clots (thrombus).
A new review of the current research clears up some of the mystery, but, unfortunately, opens up some new questions. This article will examine the science, at least as far as we know, behind these blood clots and the two COVID-19 vaccines.
COVID-19 vaccines and blood clots
Let’s start right at the top, before I get into the science of this, this COVID-19 vaccine blood clots issue only relates to the AstraZeneca and JNJ vaccines. The mRNA vaccines from Moderna and Pfizer, which use a different technology than the adenovirus-vector used by the JNJ and AstraZeneca vaccines, are not linked to these blood clots.
A few months ago, AstraZeneca reported 15 cases of deep vein thrombosis and 22 reports of pulmonary embolism, both caused by blood clots, in patients who have received their COVID-19 vaccine. These observations are out of 17 million patients who had received, at that time, the vaccine in the UK and Europe.
After reviewing these cases, researchers now call it vaccine-induced immune thrombotic thrombocytopenia (VITT), a life-threatening and mysterious condition that affects a very small number of people who have received the AstraZeneca or JNJ COVID-19 vaccines. It is estimated that VITT occurs in about 1 in 50,000 people aged under 50 who received the AstraZeneca version of the vaccine.
For a little background, these two COVID-19 vaccines use disabled adenoviruses as a ‘vector’ to shuttle mRNA, encoding for the coronavirus spike protein, into human cells. Once there, the mRNA causes the protein to be made. The immune system detects the spike protein and generates antibodies against it that are crucial for protection against coronavirus infection.
The SARS-CoV-2 virus seems to cause thrombi in many patients, which might lead one to think there is some biological plausibility to the blood clot issue. However, no live virus is used in the JNJ and AstraZeneca vaccines. These two vaccines induce the production of the spike protein for a limited time. A real infection by SARS-CoV-2 will have billions of viruses all replicating and causing havoc to the body.
Although many researchers are examining why these two COVID-19 vaccines cause VITT, no one is sure what might cause it. Furthermore, because it is so rare, it becomes difficult for researchers to determine if the vaccines are actually causing it and what might be the mechanism of action. It’s terribly frustrating.
The vaccines seem to induce an immune response against PF4, a cytokine involved in the clotting process when blood samples from vaccinated patients were reviewed. They also found that about ⅔ of the samples they received was blood clotting disorders not related to the JNJ and AstraZeneca vaccines.
The researchers have proposed several hypotheses as to why the vaccine does something to the PF4:
- Contaminants in the vaccine.
- The adenovirus vector itself (as shown in some mouse models).
- The spike protein cross-reacts with PF4.
- Other reseachers have speculated that the mRNA itself can created spike protein variants that may interact with the PF4.
- Some researchers have proposed that if the vaccine administration enters a vein (it’s supposed to be just the muscle), it could induce an immune response with PF4.
Of course, the evidence support any of these hypotheses is weak at best. Again, these blood clots are so rare that it makes it difficult for researchers to really narrow down the cause. It’s also possible that there’s some rare factor common to all of the people who express VITT that allows the vaccine to somehow interact with the PF4.
Regulatory agency responses
As I discussed with the AstraZeneca vaccine, the European Medicines Agency (EMA), the FDA for the European Union, believes that there is a plausible link between the AstraZeneca vaccine and a rare but sometimes deadly blood clots. The risk is tiny, but it appears that there is a causal link.
Canada and various provincial health agencies, such as Quebec’s, have issue guidelines regarding the COVID-19 vaccine blood clots issue, especially since the US Government has decided to provide the AstraZeneca vaccine to Canada and Mexico.
The government of Canada stated that:
This adverse event is being referred to as Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT). This entity is associated with the development of antibodies that “activate” platelets, which stimulate the formation of clots and result in thrombocytopenia. The mechanism of action is similar to heparin-induced thrombocytopenia (HIT). The exact mechanism by which the AstraZeneca vaccine triggers VIPIT is still under investigation. At this time, no other risk factors have consistently been identified in patients who develop VIPIT. This adverse event has not been identified following receipt of mRNA COVID-19 vaccines to date.
And after new data showed a slight increase in the risk of cerebral venous sinus thrombosis (CVST), a very rare thromboembolic event, health authorities in various German states made the decision to temporarily halt vaccinations for younger people after receiving more data about these clots.
Like I mentioned above, the EMA believes that a rare condition called cerebral venous sinus thrombosis (CVST), a clot that stops blood from draining from the brain. Regulators have said it is occurring among those who have received the AstraZeneca COVID-19 vaccine at a rate above what they’d expect to see in the normal population.
The EMA is reporting a total of 169 cases of CVST among the 34 million people given the AstraZeneca vaccine across Europe as of 4 April 2021. Additionally, there have been 52 other cases of rare thromboses. The EMA reported that they based its scientific review on an initial 62 cases and 18 deaths up until March 22, but continued reports did not change their assessment.
In the USA at the time that I wrote this article, six cases of CVST have occurred among women below the age of 50 and appeared between one and two weeks after vaccination. This is out of around 7 million doses of the JNJ vaccine.
The key thing to note is that a patient that presents with CVST must be treated differently than individuals with other types of thrombosis. The key characteristic of these clots is a drop in blood platelet counts, which is not observed with clots that form from the use of birth control pills and other causal factors. Thrombolytics (clot-busting drugs) and blood thinners are not indicated for these patients as they may cause a hemorrhage into the brain.
We need to put risk into some perspective, so let’s do the basic math (and please don’t conflate this with real statistics).
The risk of CVST is around 1 per 1 million people who received the JNJ COVID-19 vaccine, slightly higher with the AstraZeneca vaccine. On the other hand, the risk of death from COVID-19 is around 1,000-2,000 per 1 million who contract the disease, which is around 200X greater risk than the risk of thrombosis from the vaccine. (See Note 1)
But there’s more. We do not have information on confounding risk factors – each of these six women may have another risk factor from blood clots to smoking to some other issue.
The risk of CVST in the general unvaccinated population in the USA is around 0.5 to 1 in 1 million, so the observed risk for these types of blood clots after receiving the COVID-19 vaccine is slightly higher than expected.
Yes, the SARS-CoV-2 virus seems to cause thrombi in many patients, which might lead one to believe that there is some biological plausibility to the blood clot issue. We don’t appear to observe these thrombosis events with the Pfizer, Moderna, and JNJ vaccines, so it is possible that either there is an ingredient in the AstraZeneca or JNJ vaccines that leads to this increased risk.
At this time, it’s almost impossible to tell if there is actually a causal link between the JNJ and AstraZeneca COVID-19 vaccines and CVST. We would probably need to see over a billion people vaccinated to come to some statistically solid conclusion.
The system works
I want to make a few points about why I think the FDA and EMA are doing the right thing regarding the COVID-19 vaccine blood clots:
- The anti-vaccine mob thinks that the FDA, CDC, and other regulatory agencies don’t watch for these issues. Yes, there is a tiny risk for CVST, but regulatory agencies saw it and reacted in measure tones (the FDA “pausing” vaccination). This is what they do for all vaccines.
- As Orac pointed out, these agencies are caught between a rock and a hard place – if they did something (like they did), the anti-vaxxers will over-exaggerate the issue (which they have) and if the agencies did nothing, the anti-vaxxers will blame them for “hiding” something.
- I, and many others, remain unconvinced that there is an actual link between CVST and the two COVID-19 vaccines, but we need to check. There is a curious issue with thrombocytopenia (low platelets) and these clots, which is almost counterintuitive and is not well understood.
- The “pause” also gives time to make recommendations to physicians on how to treat this type of CVST – that (1), it should not be treated with blood thinners like heparin, and (2) the association between the CVST and thrombocytopenia may indicate some sort of immune response.
- This is how science works, take an observation and create a hypothesis from it – do the COVID-19 vaccines cause CVST. Then analyze the data in a scientific manner to determine if we can accept or reject the hypothesis. That’s what the CDC is trying to do.
- All drugs, including vaccines, have risks – what the CDC, FDA, EMA, and others are saying is that the benefits, saving lives, far exceed the risks of CVST. However, if these agencies can make recommendations to reduce the risk, say a certain demographic group with certain other risk factors (say smoking or use of birth control pills) is excluded from using the vaccine, that is a good thing. That’s how the system is supposed to work.
I completely disagree with my peers who are dismissing this risk out of hand because it’s a tiny risk. That plays into the hands of the ignorant anti-vaxxers who wouldn’t know math and statistics if it kissed them on the mouth.
If there is a known risk of CVST, then everyone should know about it. And, although it makes my job hard, I will do the best I can to explain that it’s still safer than getting COVID-19, and it’s still very safe irrespective of the risk-benefit ratio.
The regulatory agencies made the right choices, and the system works.
Of course, regulatory authorities, public health organizations, AstraZeneca, and others will not ignore this, and they will all work together to investigate whether there is an actual link between blood clots and the AstraZeneca COVID-19 vaccine.
If the link between these COVID-19 vaccines and blood clots holds up, the incidence is so low that the benefits, preventing COVID-19, far exceed this risk of VITT.
All vaccines have some risks, almost always very minor ones – anti-vaxxers frequently fail to understand the vaccine risk-benefit equation by rounding up rare events to 100% and rounding down effectiveness to 0%. This is a perfect example of the Nirvana fallacy, which states that if something isn’t perfect, it’s bad.
All countries that have approved these vaccines are monitoring the situation closely, and they have issued recommendations in case VITT is observed. For example, the CDC has issued clinical recommendations for the JNJ vaccine after a pause in its use earlier in 2021 because of blood clots.
- My calculated numbers for these risks are based on the infamous back of the napkin analyses. Once peer-reviewed papers are published, we will know the precise risk difference between vaccinated unvaccinated groups.
- Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007 Apr;44(2):62-9. doi: 10.1053/j.seminhematol.2007.02.004. PMID: 17433897; PMCID: PMC2020806.
- Greinacher A, Selleng K, Mayerle J, Palankar R, Wesche J, Reiche S, Aebischer A, Warkentin TE, Muenchhoff M, Hellmuth JC, Keppler O, Duerschmied D, Lother A, Rieg S, Gawaz M, Mueller KAL, Scheer C, Napp M, Hahnenkamp K, Lucchese G, Vogelgesang A, Flöel A, Lovreglio P, Stufano A, Marschalek R, Thiele T. Anti-Platelet Factor 4 Antibodies Causing VITT do not Cross-React with SARS-CoV-2 Spike Protein. Blood. 2021 Jul 19:blood.2021012938. doi: 10.1182/blood.2021012938. Epub ahead of print. PMID: 34280256; PMCID: PMC8294553.
- MacNeil JR, Su JR, Broder KR, Guh AY, Gargano JW, Wallace M, Hadler SC, Scobie HM, Blain AE, Moulia D, Daley MF, McNally VV, Romero JR, Talbot HK, Lee GM, Bell BP, Oliver SE. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients – United States, April 2021. MMWR Morb Mortal Wkly Rep. 2021 Apr 30;70(17):651-656. doi: 10.15585/mmwr.mm7017e4. PMID: 33914723; PMCID: PMC8084127.
- Othman M, Labelle A, Mazzetti I, Elbatarny HS, Lillicrap D. Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance. Blood. 2007 Apr 1;109(7):2832-9. doi: 10.1182/blood-2006-06-032524. PMID: 17148587.
- Pavord S, Scully M, Hunt BJ, Lester W, Bagot C, Craven B, Rampotas A, Ambler G, Makris M. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. N Engl J Med. 2021 Aug 11. doi: 10.1056/NEJMoa2109908. Epub ahead of print. PMID: 34379914.
- Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, Wiedmann M, Aamodt AH, Skattør TH, Tjønnfjord GE, Holme PA. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. 2021 Jun 3;384(22):2124-2130. doi: 10.1056/NEJMoa2104882. Epub 2021 Apr 9. PMID: 33835768; PMCID: PMC8112568.