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AstraZeneca COVID Vaccine and blood clots

by jmh1 min read15th Mar 202120 comments

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Covid-19
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Any thoughts on the reality of the new reports about the potential that the vaccine exposes receivers to a risk of blood clot problems?

I did a quick Google Scholar search but nothing seemed to apply just looking at the title listing in the summary page. The stories I've seen reported in the press seem weak on any actual details about how that vaccine might produce the problem while it seems unheard of with the other vaccines. Incident rates seem really small so it makes me wonder. Are we really getting the real story here or is this a case of some chicken little worries about the sky falling?

I also wonder, given a prior post on the correlation implying some causality, if that thought should not shift one's views towards not really getting the whole story. If so, just what "the story" might actually be.

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This comes from an AstraZeneca press release, but it sounds like there's strong evidence that the AZ vaccine doesn't cause blood clots and this is a typical case of "if anything bad happens after you take a drug, it gets reported as a side-effect", which is why one of the possible adverse effects of the Moderna vaccine is getting struck by lightning:

A careful review of all available safety data of more than 17 million people vaccinated in the European Union (EU) and UK with COVID-19 Vaccine AstraZeneca has shown no evidence of an increased risk of pulmonary embolism, deep vein thrombosis (DVT) or thrombocytopenia, in any defined age group, gender, batch or in any particular country.

So far across the EU and UK, there have been 15 events of DVT and 22 events of pulmonary embolism reported among those given the vaccine, based on the number of cases the Company has received as of 8 March. This is much lower than would be expected to occur naturally in a general population of this size and is similar across other licensed COVID-19 vaccines.

(Emphasis added)

From Twitter, it looks like the rates of clotting-related issues in UK recipients of the AstraZeneca and Pfizer/BioNTech vaccines are essentially indistinguishable.

An update to this comment: there is now some evidence to suggest the rates of cerebral venous sinus thrombosis are substantially different in UK recipients of the two vaccines. It is a very low rate (30 in 28 million), but there does seem to be a real difference there.

If there's an actual risk of blood clot problems, we should see something similar reported in the UK, given the millions of doses they already used.

We don't see any similar reports coming from the UK. The opposite seems true (BBC).

Is the UK hiding this kind of news? I doubt.

Are there problem only outside of the UK? 
If this is the case, "the story" might actually be some handling/logistic problem in the vaccines production/transportation/storage in other countries that turns some batches bad.

If this is the case we should see higher % of problems where the batches are mishandled.
I could not find numbers about this, it looks like at the first problem some countries are halting the distribution of entire batches.

A clearer smoking gun would be multiple people having blood clots problems after receiving doses from the same batch.
The size of the batch would help estimate how unlikely that event is.

Italy halted ABV5811 and ABV2856, but unfortunately I could not find how big these batches actually are. If you have any idea I'd be glad to know.

I'd feel completely safe to get a vaccine in the UK.
In lack of the specific batch information, I'd feel safe outside of the UK too.

I've found a post from EMA claiming:
 

Batch ABV5300 was delivered to 17 EU countries and comprises 1 million doses of the vaccine. 

but still no signal on how big is the batch single countries get.

Off the top of my head, it could easily be the case that we still need to rule out that the groups getting the vaccine are already more prone to blood clots. In particular, I seem to remember some talk about Covid infections leading to blood clots, and many of the early vaccinations have been given to folks most likely to be exposed to Covid. We've also seen that "asymptomatic" (referring specifically to the symptoms of cough, fever, & anosmia) Covid seems to be really common in the group of all infections.

It's not much of a stretch to guess that -- if the blood clot problem turns out to be real -- it may be at least partly because of those "asymptomatic" infections among the groups we've targeted for early vaccination specifically because they are more likely to be exposed (and therefore more likely to have already been infected without knowing) than other groups.

There's a Twitter thread claiming that there is statistical evidence that blood clots are unusually common in Germany after getting the AstraZeneca vaccine:

The PEI ran an "observed-versus-expected analysis", comparing the # of such cases expected without vaccination in a 14-day period with the # of cases reported in those vaccinated with #AstraZeneca (1.6 million) in Germany. About 1 case would be expected, 7 were observed

I still think stopping vaccination is insane for several reasons:

  • According to this source, approximate 200 people are dying of COVID per day in Germany. Even if we assume that 6 out of every 1.6 million people who get the AZ vaccine get blood clots and die, that would be 365 deaths total in Germany or 2 days worth of COVID deaths.

  • According to this source, the survival rate of cerebral venous-sinus thrombosis is ~95%, and taking that into account, even if the 6 / 1.6 million number is correct, we would expect only 1/20th of those people to die of it, leading to approximately 20 people in Germany dying of this (again, vs ~200 people per day dying of COVID).

  • I'm still very skeptical that this 6 / 1.6 million number is actually correct since it's a very small number and small numbers are possible to get by chance, especially if you're doing multiple comparisons: Why are we only looking at the number for Germany? Wouldn't this be reported if it had happened in France, or the UK, or...?

A couple of days ago I came across this deposition to the "German Corona Extra-Parliamentary Inquiry Committee", by Dr. Vanessa Schmidt-Kruger, who describes herself as "a cell biologist and my specialist field is the functional characterisation and elucidation of proteins".

She enumerates a range of concerns with the BioNTech vaccine, including purity; toxicity of lipid nanoparticles; dosing and long-term immune effects. There is an almost throw-away comment in there to the effect of: "...it has also been found that when the LNPs are transported in the blood then thromboses can occur, or haemolysis – haemolysis means the sudden dissolution of erythrocytes, i.e. red blood cells, this causes hypoxia."

I'm not in a position to evaluate any of this -- the deposition is quite long, and technical (altho note that the second half of the doc is just the German version). The presentation.. somewhat twinges my "this might be crackpot" aesethetic sense (as per naming-the-nameless), but I can't dismiss it out of hand based on that.

There is an almost throw-away comment in there to the effect of: "...it has also been found that when the LNPs are transported in the blood then thromboses can occur, or haemolysis – haemolysis means the sudden dissolution of erythrocytes, i.e. red blood cells, this causes hypoxia."

Googling a bit finds articles that do discuss polyethylene glycol (the LNP used in the mRNA vaccines) can sometimes have effects of thromboses):

https://www.sciencedirect.com/science/article/abs/pii/0049384874900243

It's probably mainly a question of how serious that concern happe... (read more)

AstraZeneca is not a RNA based vaccine, so does not contain any LNPs as far as I know.

9 comments, sorted by Highlighting new comments since Today at 8:21 AM

Today's statement by the Paul-Ehrlich-Institut (PEI), Germany's vaccine and pharmaceutical regulatory agency (translation by deepl, emphasis in the quote is mine)

"The Paul Ehrlich Institute informs - Temporary suspension of vaccination with COVID-19 vaccine AstraZeneca

Following intensive consultations on the serious thrombotic events that have occurred in Germany and Europe, the Paul Ehrlich Institute recommends the temporary suspension of vaccinations with the COVID-19 vaccine AstraZeneca.

Compared to the status on March 11, 2021, additional cases (as of Monday, March 15, 2021) have now been reported in Germany. Analyzing the new data status, the experts of the Paul Ehrlich Institute now see a striking accumulation of a special form of very rare cerebral venous thrombosis (sinus vein thrombosis) in connection with a deficiency of blood platelets (thrombocytopenia) and bleeding in temporal proximity to vaccinations with the COVID-19 vaccine AstraZeneca.

The data are being further analyzed and evaluated by the European Medicines Agency (EMA).

Vaccinations with AstraZeneca's COVID-19 vaccine in Germany will be suspended until the EMA's evaluation is complete. Today's decision affects both initial and follow-up vaccinations.

The Paul Ehrlich Institute advises that individuals who have received AstraZeneca's COVID-19 vaccine and feel increasingly unwell more than four days after vaccination - for example, with severe and persistent headache or pinpoint bleeding of the skin - should seek medical treatment immediately." PEI

This is the key point. All other comments are about the base rates of general forms of thrombosis, but the concern is about a rare, special type. It is actually not inconceivable that the risk of death for young people from this vaccine might be higher than the risk from Covid-19. 

Yes, that was the main argument for the decision of the PEI - the risk for a group that does not profit as much from a vaccine as older people.

If I had to guess:

  1. The women had taken oral contraceptives.
  2. Maybe this group will be excluded from this specific vaccine in the future.

(But it is just a guess, I am no expert).

Here additional background information from the German PEI (translation by deepl):

"In seven cases (as of 03/15/2021), a specific form of severe cerebral venous thrombosis associated with platelet deficiency (thrombocytopenia) and bleeding has been identified in temporal association with vaccination with AstraZeneca COVID-19 vaccine.

It is a very serious disease that is also difficult to treat. Of the seven affected individuals, three had died.

The affected individuals had ages ranging from about 20 to 50 years.

Six of the affected individuals had a particular form of cerebral venous thrombosis, namely sinus vein thrombosis. All six individuals were younger to middle-aged women (see above). Another case with cerebral hemorrhage in platelet deficiency and thrombosis was medically very comparable. All cases occurred between four and 16 days after vaccination with AstraZeneca COVID-19 vaccine. This presented as a comparable pattern.

The number of these cases after AstraZeneca COVID-19 vaccination is statistically significantly higher than the number of cerebral venous thromboses that normally occur in the unvaccinated population. For this purpose, an observed-versus-expected analysis was performed, comparing the number of cases expected without vaccination in a 14-day time window with the number of cases reported after approximately 1.6 million AstraZeneca vaccinations in Germany. About one case would have been expected, and seven cases had been reported.

The younger to middle-aged group of people affected by the severe cerebral venous thromboses with platelet deficiency is not the group of people at high risk for a severe or even fatal COVID-19 course.

In addition to the experts from the Paul Ehrlich Institute, other experts in thrombosis, hematology, and an adenovirus specialist were consulted with the details of the reported cases. All experts were unanimous in their opinion that a pattern could be discerned here and that a connection between the reported above-mentioned diseases and the AstraZeneca vaccination was not implausible.

After an overall review and consideration of the above facts, the Paul Ehrlich Institute recommended that vaccination with the AstraZeneca COVID-19 vaccine be suspended in Germany as a precautionary measure in order to further analyze the cases. The German Federal Ministry of Health (BMG) has followed this recommendation. The Pharmacovigilance Risk Assessment Committee (PRAC) at the European Medicines Agency (EMA) will review during the week of March 15, 2021, whether and how the new findings affect the benefit-risk profile of the AstraZeneca COVID-19 vaccine and the EU approval of the vaccine."

Source: PEI

My prior would be that there probably is no blood clot problem. With the HPV vaccine there were the same fears and a large study showed that this was not the case (source: NPR ).

Blood clots are a somewhat common problem, see e.g. Data and Statistics on Venous Thromboembolism so cases of that are to be expected.

Of course, it is possible that this time it is different and of course, it should be investigated. However, I think that the probability is high that stopping using this vaccine while investigating will kill much more people than its continuous use.

Edit: Having thought about it a little bit longer, I am not so sure anymore about the last paragraph above. Because there is a second order risk: that the unlikely, I believe, case is true that the vaccine causes dangerous blood clots, but the public is told to get vaccinated anyway - possibly leading to a major loss of confidence in all vaccines once this is clear, and by reducing vaccination rates killing many, many more people than the blood clots.

My intuition is that this is an unlikely worry. The people who actually understand the math on vaccines might be slightly more cautious, but won't actually care, and will keep saying that vaccinating despite the blood clots was the right choice. While the people who are currently scared of vaccines won't really care, and will just point to this as an additional reason to believe what they already believed. 

This neglects to account for a large group of people who have no opinion and will be swayed by any news, positive or negative. Overcoming a formed opinion is going to be harder.

Is there a source that shows there's even a correlation? Please link one if there is - perhaps I missed it. The reports I've seen don't suggest any - e.g. bmj report.

From what (little) I've seen, this seems to be evidence for the hypothesis "Anecdotes frequently cause officials with bad incentives to make harmful decisions".

I probably could have worded things much better on that. No, to my knowledge no one has claimed or performed some type of correlation calculations on the data. The reference here was to one of the LW posts a little while back.

The adenovirus might do all sorts of things that we don't know beforehand in some of the patients. It's very worthwhile to worry about risks of medical interventions. That's especially true when it's easy to counteract the risks when you know they are there, which is the case with blood clots problems. 

Edit: I wrote the above after talking with a doctor friend yesterday about vaccines who said. Maybe, I have to give me patients who are generally at risk for blood clots problems anti-blood clot drugs when giving them the vaccine.

Now, I saw and Germany where I live stopped use of the vaccine which seems like a digusting overreaction.