Oxford Vaccine Clotting

  • Thread starter bhobba
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I agree with the overall point however it is not accurate to say that it is at the same level of occurrence as the general population, or at least it is misleading.

Correct.

But here is something interesting - the following includes both CVT and PVT on both the AZ and mRNA vaccines like Pfizer - see from about 8.30:

A couple of comments:

1. The chance of getting blood clots is significantly higher than the vaccine if you get Covid. So if Covid is really raging where you are - get vaccinated, and you have actually reduced your risk of clots.

2. The incidence of CVT is about, in the general population, .41 in a million in a two week period. Oxford is 5 in a million; mRNA vaccines are 4.1 in a million. While treatable, it has about a 20% fatality rate. So yes, mRNA vaccines are better in this study - but only slightly so. The question then is, why is the mRNA vaccine recommend due to CVT? Others may know more about this - my suspicion is we have vaccinated mostly older age groups at the moment, and for younger people, the odds change - just a guess.

3. We also have PVT, which also has a horrid death rate of 18.8%. The comparison between the vaccines is 44 per million for Pfizer and just 1.6 per million for Az. That is markedly in favour of AZ.

The government reactions and the above data are not clearly linked IMHO. I will not comment on it, except more research is obviously urgently required, e.g. the data depending on age. If offered either, I would take the AZ based on the above. But I have to say you should always discuss it with your doctor first. And also, if Covid is raging where you are, like PNG or India, forget about the clots from the vaccine - it is much less than if you got Covid. Where that leaves me in Aus is interesting. It is eliminated but can come back at any time. Personally, I would keep doing what we are doing, where for some reason, we are slowly vaccinating but still producing 1 million doses a week - much more than is being used. CSL must store the rest - you need to store some for the second dose, but the difference between those made and used is much greater than that. A few weeks ago, I heard 2.8 million doses were in storage - probably more now. If it comes back, mass vaccinate like crazy using vaccination hubs, chemists, physiotherapists etc., with the vaccine in storage.

The following gives an interesting comparison on risks:
https://www.bbc.com/news/world-56763490

Notice it gives a rate of serious harm from the vaccine as 11 in a million for the young than 4 in a million over 55. I would like to see that compared to mRNA vaccines. But when PVT is taken into account, that 44 in a million chance still seems to favour the AZ :rolleyes::rolleyes::rolleyes::rolleyes:.

Thanks
Bill
 
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  • #27
Laroxe
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Yes this is an incredibly important issue, the vector based vaccines which are most associated with these abnormal clots are an important part of the current global vaccine drive. Part of the problem in the investigation is the rarity of the condition, its only very recently that there has been sufficient data to suggest there is an increased risk.

It may be that heparin-induced thrombocytopenia (HIT) may be the best model for understanding this unusual set of symptoms in which bleeding and hyper coagulation co-exist. This condition occurs rarely in people treated with heparin, an anticoagulant and tends to be transient. It appears that heparin can trigger the production of antibodies that bind to receptors on the surface of platelets destroying them. This destruction causes the release of other clotting factors, the loss of the platelets reduces the ability of the blood to clot, the clotting factors increase clotting, this would explain the rather contradictory symptoms. This idea has been supported by antibody studies in people affected post vaccination and currently guides treatment guidelines.
There is a particular problem in investigating very rare adverse events, particularly ones that are likely to have complex causes, particularly when as Mary's post points out there are still questions about whether the association is real. Its certainly important to try and identify what parts of the vaccine might be responsible but we already know that immune thrombocytopenia can occur with all the Covid vaccines and several others, but this doesn't explain the differences seen in the occurrence of abnormal clotting between the mRNA and vector based vaccines.
We also know that in studies of CVT prior to Covid, several other risk factors have been suggested that may also influence the vaccine response, these might include Obesity, pregnancy, other clotting or autoimmune disorders, the contraceptive pill, age and gender. Putting some sort of picture together when we have so little data may be a long job.

Despite these issues the fact remains that these vaccines are important until more become widely available, they are effective and these adverse effects are extremely rare. Unfortunately, people pay particular attention to possible risks but fail to consider this risk in the context of the pandemic. While most scientific advisory groups suggest the vaccination program should continue to use these vaccines, Covid 19 continues to kill thousands across the world, Governments have restricted their use. Often these restrictions are based on findings from early studies which rapidly become obsolete.
Not only do people pay attention to indicators of risk, they also remember them, it seems unlikely that new evidence will restore faith in this group of vaccines. As there is a large number of potential new vaccines that use a variety of delivery platforms we may have to wait before adequate control of the pandemic is achieved.
This is an explainer from Nature which might add to the valuable information in Mary's post

https://www.nature.com/articles/d41586-021-00998-w
 
  • #28
Ygggdrasil
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2. The incidence of CVT is about, in the general population, .41 in a million in a two week period. Oxford is 5 in a million; mRNA vaccines are 4.1 in a million. While treatable, it has about a 20% fatality rate. So yes, mRNA vaccines are better in this study - but only slightly so. The question then is, why is the mRNA vaccine recommend due to CVT? Others may know more about this - my suspicion is we have vaccinated mostly older age groups at the moment, and for younger people, the odds change - just a guess.
These figures are inconsistent with data from the CDC that I posted earlier:
1618929621468.png

(source: April 14 meeting of the CDC Advisory Committee on Immunization Practices: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04/03-COVID-Shimabukuro-508.pdf)
 
  • #29
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These figures are inconsistent with data from the CDC that I posted earlier:
Yes, they are. I will try and get the preprint it came from so an appraisal can be made of data very much at odds. Hang on a minute.

Added Later:
Ok - here is the news article about it from Oxford:
https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines

At the bottom is the link to the paper:
https://osf.io/a9jdq/

Hopefully, we can get to the bottom of it because, to be blunt such a divergence is - well - bizarre.

Tentatively my take is what was said at the end of the paper:
'The rarity of CVT in all populations means that larger sample sizes are required to confirm the results, and complementary study designs are needed to aid interpretation. Nevertheless, the current data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize and inform debate about the risk-benefit ratio for current COVID-19 vaccines.'

Also very surprising was for mRNA vaccines the high incidence of PVT compared to AZ. The difference was large.

Thanks
Bill
 
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  • #30
Ygggdrasil
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Yes, they are. I will try and get the preprint it came from so an appraisal can be made of data very much at odds. Hang on a minute.

Added Later:
Ok - here is the news article about it from Oxford:
https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines

At the bottom is the link to the paper:
https://osf.io/a9jdq/

Hopefully, we can get to the bottom of it because, to be blunt such a divergence is - well - bizarre.

Tentatively my take is what was said at the end of the paper:
'The rarity of CVT in all populations means that larger sample sizes are required to confirm the results, and complementary study designs are needed to aid interpretation. Nevertheless, the current data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize and inform debate about the risk-benefit ratio for current COVID-19 vaccines.'

Also very surprising was for mRNA vaccines the high incidence of PVT compared to AZ. The difference was large.

Thanks
Bill

My criticism of the estimate in the paper is that the denominator for the estimate of the incidence of CVT after COVID-19 vaccination is likely wrong.

The paper looked at anonymized electronic health records from 59 healthcare organizations primarily in the USA. These organizations cover 81 million patients according to the authors. Their data looks at the population of people who received at least one dose of a COVID-19 vaccination before March 25, 2021. According to the CDC, 95 million people had received at least one dose of a COVID-19 vaccination by March 25. This amounts to about 29% of the US population. However, their dataset only has N = 489,871 patients who received a COVID-19 vaccination (0.6% of the 81 million patients). They observed 2 cases of CVT in this cohort, which is the source of the 4.1 per million statistic. However, only 490 thousand vaccinated individuals in this cohort is an implausibly low number; the expected number of vaccinated individuals should be ~23 million, which would lower the incidence of CVT to ~0.09 per million in the two weeks after vaccination.

This discrepancy in the observed number vaccinated versus the expected number vaccinated likely comes about because vaccinations in the US are being distributed through a number of means, not necessarily through one's primary healthcare provider (e.g. thorough pharmacies or mass vaccination sites run by the government). Therefore, patients who got vaccinated through these means would not have a record of vaccination in these electronic health records. This information would only be entered if the patient had to go to their healthcare provider for another reason. Thus, the method has a selection bias for vaccinated people who experienced adverse events. This error could have come about because the authors are from Oxford University in the UK, so they may not be familiar with how the US healthcare and vaccine distribution system has been operating.

Assuming that ~29% of the patient population was vaccinated (as opposed to the 0.6% they observe), the risk of CVT in the sample would drop significantly (by a factor of ~50, which would bring the incidence of CVT in the vaccinated cohort below the expected incidence of CVT).

I will write to the authors of the study to notify them of this major flaw in their data.
 
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  • #31
Laroxe
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My criticism of the estimate in the paper is that the denominator for the estimate of the incidence of CVT after COVID-19 vaccination is likely wrong.

The paper looked at anonymized electronic health records from 59 healthcare organizations primarily in the USA. These organizations cover 81 million patients according to the authors. Their data looks at the population of people who received at least one dose of a COVID-19 vaccination before March 25, 2021. According to the CDC, 95 million people had received at least one dose of a COVID-19 vaccination by March 25. This amounts to about 29% of the US population. However, their dataset only has N = 489,871 patients who received a COVID-19 vaccination (0.6% of the 81 million patients). They observed 2 cases of CVT in this cohort, which is the source of the 4.1 per million statistic. However, only 490 thousand vaccinated individuals in this cohort is an implausibly low number; the expected number of vaccinated individuals should be ~23 million, which would lower the incidence of CVT to ~0.09 per million in the two weeks after vaccination.

This discrepancy in the observed number vaccinated versus the expected number vaccinated likely comes about because vaccinations in the US are being distributed through a number of means, not necessarily through one's primary healthcare provider (e.g. thorough pharmacies or mass vaccination sites run by the government). Therefore, patients who got vaccinated through these means would not have a record of vaccination in these electronic health records. This information would only be entered if the patient had to go to their healthcare provider for another reason. Thus, the method has a selection bias for vaccinated people who experienced adverse events. This error could have come about because the authors are from Oxford University in the UK, so they may not be familiar with how the US healthcare and vaccine distribution system has been operating.

Assuming that ~29% of the patient population was vaccinated (as opposed to the 0.6% they observe), the risk of CVT in the sample would drop significantly (by a factor of ~50, which would bring the incidence of CVT in the vaccinated cohort below the expected incidence of CVT).

I will write to the authors of the study to notify them of this major flaw in their data.
I think your first sentence summarizes the real problem, people are trying to make sense of very low frequency events and currently each new data set seems to muddy the water rather than clarify things. Hopefully given time the picture will become more accurate. Remember we still have the very basic argument about whether this is even a real effect, the data we have is so contaminated by other effects. There seems to be some basic differences in many of the groups studied these might include age, gender, risk of exposure, dose of exposure, ethnicity etc, so we end up with some big differences in findings.
 
  • #32
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I will write to the authors of the study to notify them of this major flaw in their data.
I think you are correct. In fact, taking into account your analysis, I am not sure it would pass peer review. That is the problem with this pandemic - things move so fast papers before peer-review are discussed. They then get discussed in the media. A talk show discussed this paper last night where the host observed just who do you believe with so much conflicting information around. I well remember the egg I had on my face when I argued with Chemisttre about the value of face masks. We had experts, a number with Nobel's in Epidemomology like Peter Doherty, who said face masks are useless. I was wrong - Chemisttre was right:
https://www.nature.com/articles/d41586-020-02801-8

Despite the evidence of their value, there are still people that say they are useless. It's a problem - maybe even one of the biggest issues with this pandemic.

As an aside, I did not know that about the way things are done in the US either. You live and learn. Here in Aus we have a centralised database of everyone's Covid vaccine - what little has been done :nb):nb):nb):nb).

Thanks
Bill
 
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  • #33
Ygggdrasil
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Useful slide from the April 23 ACIP meeting that puts the relative risk of thrombotic thrombocytopenia from the Johnson & Johnson vaccine into context with other vaccine-related adverse events:
1619374827373.png

(source)
 

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