AstraZeneca (Latest Trials)

[Bouleversee]

The German government yesterday suspended use of the AZ jab for under-60s after more apparent concerns over blood clots.

I am totally confused. Germany has had about a 12% roll out with a large percentage Pfizer (sorry don't know the actual percentages). Are they basing their latest decision on their limited AZ national data or data from elsewhere ie data from extensive analysis in say Scotland?

But how many non frontline people under 60 (anywhere) have been given AZ? Surely just 'at risk' people. Thus as far as I can see, only frontline staff and 'vulnerables' can actually make up this cohort. Any possibility of 'links' between these groups and blood clots (above the expected average in the overall population)?

I have a professional grounding in statistical analysis and yet am somewhat confused as to the robustness of statistical conclusions being drawn.

T7

The report mentioned 9 cases in Germany and Austria. The highly vulnerable here would have had the Pfizer vaccine but by now quite a lot of non-front line people will have had the AZN jab including, last week, my 52 year old daughter which is slightly concerning since she has a prothrombin factor and is not being monitored in any way. I wonder whether she ought to have some blood tests at some point to measure platelet count etc.

[Dod101]

The German government yesterday suspended use of the AZ jab for under-60s after more apparent concerns over blood clots.

I am totally confused. Germany has had about a 12% roll out with a large percentage Pfizer (sorry don't know the actual percentages). Are they basing their latest decision on their limited AZ national data or data from elsewhere ie data from extensive analysis in say Scotland?

But how many non frontline people under 60 (anywhere) have been given AZ? Surely just 'at risk' people. Thus as far as I can see, only frontline staff and 'vulnerables' can actually make up this cohort. Any possibility of 'links' between these groups and blood clots (above the expected average in the overall population)?

I have a professional grounding in statistical analysis and yet am somewhat confused as to the robustness of statistical conclusions being drawn.

T7

Well my 54 year old daughter had her first Oxford AstraZeneca jab yesterday and she is in no special category. Many of her friends of about the same age have had theirs as well.

That was in Edinburgh and that health board has not been notably leading the way.

Dod

[terminal7]

Interesting - but these examples are very recent - what evidence that any large numbers of under 60s - ex front line ex vulnerable - were given AZ at least say 3 weeks plus ago?

T7

[Bouleversee]

The German government yesterday suspended use of the AZ jab for under-60s after more apparent concerns over blood clots.

I am totally confused. Germany has had about a 12% roll out with a large percentage Pfizer (sorry don't know the actual percentages). Are they basing their latest decision on their limited AZ national data or data from elsewhere ie data from extensive analysis in say Scotland?

But how many non frontline people under 60 (anywhere) have been given AZ? Surely just 'at risk' people. Thus as far as I can see, only frontline staff and 'vulnerables' can actually make up this cohort. Any possibility of 'links' between these groups and blood clots (above the expected average in the overall population)?

I have a professional grounding in statistical analysis and yet am somewhat confused as to the robustness of statistical conclusions being drawn.

T7

The report mentioned 9 cases in Germany and Austria. The highly vulnerable here would have had the Pfizer vaccine but by now quite a lot of non-front line people will have had the AZN jab including, last week, my 52 year old daughter which is slightly concerning since she has a prothrombin factor and is not being monitored in any way. I wonder whether she ought to have some blood tests at some point to measure platelet count etc.

P.S. to previous post: The report is rather difficult to unscramble for a layman. It leaves lots of questions so far as I am concerned.

I can't help wondering whether this issue played any part in the govt's decision to suspend vaccinations here for the under fifties.

[Bouleversee]

Interesting - but these examples are very recent - what evidence that any large numbers of under 60s - ex front line ex vulnerable - were given AZ at least say 3 weeks plus ago?

T7

I can't give you any statistics but I do know quite a few people under 60 who had it some weeks ago.

[GrahamPlatt]

https://www.ahajournals.org/doi/10.1161 ... 116.013617

This study published July 2016

“The incidence of cerebral venous thrombosis (CVT) varies between studies, but it is estimated to be between 2 and 5 per million per year. A recent study in the Netherlands with comprehensive ascertainment suggested a much higher incidence....


In our population of 953 390 adults, this represented an incidence of 15.7 million per year”

[redsturgeon]

I'm sure I remember reading that these younger patients were front line medical staff, hence the younger age range.

John

[GrahamPlatt]

There is a natural cohort of people with a thrombogenic tendency. It tends to be expressed in young women on taking the oral contraceptive pill, either in the form of pulmonary embolism or stroke. A rare, but well documented “side effect” of the OCP. But we don’t test these young ladies beforehand.

[Bouleversee]

There is a natural cohort of people with a thrombogenic tendency. It tends to be expressed in young women on taking the oral contraceptive pill, either in the form of pulmonary embolism or stroke. A rare, but well documented “side effect” of the OCP. But we don’t test these young ladies beforehand.

Why not? I should have thought it would make sense to test them before and at an appropriate interval after starting on OCP and the same as regards the vaccine with people who were known to have the genetic prothrombin factor.

I wonder how many of those women who came to grief after the vaccination were on OCP or had a prothrombin factor. It hasn't even been discussed so far as I am aware.

[GrahamPlatt]

https://ashpublications.org/blood/artic ... raceptives

[GrahamPlatt]

What we do not (yet) know is the incidence of CVT etc in those having received the other vaccines. Surprising lack of clarity there*.. or perhaps it’s justifiably “commercially sensitive” in those cases, given they’re being sold at profit.

*by which I mean, that given the natural background incidence, it seems vanishingly unlikely there haven’t been any. Strange we haven’t heard of even one.

[Julian]

What we do not (yet) know is the incidence of CVT etc in those having received the other vaccines. Surprising lack of clarity there*.. or perhaps it’s justifiably “commercially sensitive” in those cases, given they’re being sold at profit.

*by which I mean, that given the natural background incidence, it seems vanishingly unlikely there haven’t been any. Strange we haven’t heard of even one.

Exactly my confusion. I’m not sure it’s legal for such side effect data to be commercial in confidence. I would have thought that a licence is a license (emergency use or full marketing licence) regardless of whether it’s at profit or not, or for an orphan indication, so surely full disclosure of side effects must be on the table? Maybe there is a grace period whilst the licence holder tries to fill in gaps in the reporting and do the stats? Might that be being pushed to the limit by some companies to delay release? No idea but I really am surprised that a gazillion credible media organisations aren’t demanding answers from Pfizer and other regarding their incidences of these rare clot conditions. Maybe it’s zero % but if so why not release the data?

- Julian

[servodude]

What we do not (yet) know is the incidence of CVT etc in those having received the other vaccines. Surprising lack of clarity there*.. or perhaps it’s justifiably “commercially sensitive” in those cases, given they’re being sold at profit.

*by which I mean, that given the natural background incidence, it seems vanishingly unlikely there haven’t been any. Strange we haven’t heard of even one.

Exactly my confusion. I’m not sure it’s legal for such side effect data to be commercial in confidence. I would have thought that a licence is a license (emergency use or full marketing licence) regardless of whether it’s at profit or not, or for an orphan indication, so surely full disclosure of side effects must be on the table? Maybe there is a grace period whilst the licence holder tries to fill in gaps in the reporting and do the stats? Might that be being pushed to the limit by some companies to delay release? No idea but I really am surprised that a gazillion credible media organisations aren’t demanding answers from Pfizer and other regarding their incidences of these rare clot conditions. Maybe it’s zero % but if so why not release the data?

- Julian

I did stumble across a paper/report suggesting that the HIT style symptoms much be caused by the Adenovirus part
- whether that might be why, or because, it's not been observed in the mRNA vaccines wasn't clear
...and I can't find it in my history at present
-sd

[Julian]

What we do not (yet) know is the incidence of CVT etc in those having received the other vaccines. Surprising lack of clarity there*.. or perhaps it’s justifiably “commercially sensitive” in those cases, given they’re being sold at profit.

*by which I mean, that given the natural background incidence, it seems vanishingly unlikely there haven’t been any. Strange we haven’t heard of even one.

Exactly my confusion. I’m not sure it’s legal for such side effect data to be commercial in confidence. I would have thought that a licence is a license (emergency use or full marketing licence) regardless of whether it’s at profit or not, or for an orphan indication, so surely full disclosure of side effects must be on the table? Maybe there is a grace period whilst the licence holder tries to fill in gaps in the reporting and do the stats? Might that be being pushed to the limit by some companies to delay release? No idea but I really am surprised that a gazillion credible media organisations aren’t demanding answers from Pfizer and other regarding their incidences of these rare clot conditions. Maybe it’s zero % but if so why not release the data?

- Julian

I did stumble across a paper/report suggesting that the HIT style symptoms much be caused by the Adenovirus part
- whether that might be why, or because, it's not been observed in the mRNA vaccines wasn't clear
...and I can't find it in my history at present
-sd

You might be thinking of the paper that monabri posted a link to on this thread today...

It appears that the platelet-activating antibodies induced by vaccination bind to non-complexed PF4 alone, also noted in some sera from patients with heparin-induced thrombocytopenia12. Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or if the vaccine itself triggers the formation of platelet activating antibodies cannot be distinguished by this study. Enhanced reactivity of the sera in vitro in the presence of AZD1222 could be explained by direct binding of the virus to platelets. Adenovirus binds to platelets and can cause platelet preactivation.

[ Source (thanks monabri) - https://www.researchsquare.com/article/rs-362354/v1 ]

When looking for silver linings after this wretched pub-closing pandemic the acceleration in the development of mRNA vaccine technology would be on my list. Obviously an awful lot of complex science and manufacturing technology was involved in making it work in practice but looking at it in the abstract I find the elegant simplicity very satisfying.

- Julian

[Bouleversee]

https://ashpublications.org/blood/article/107/7/2766/132046/Thrombophilic-abnormalities-oral-contraceptives

Thank you for the link, which I shall study.

[servodude]

You might be thinking of the paper that monabri posted a link to on this thread today...

It appears that the platelet-activating antibodies induced by vaccination bind to non-complexed PF4 alone, also noted in some sera from patients with heparin-induced thrombocytopenia12. Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or if the vaccine itself triggers the formation of platelet activating antibodies cannot be distinguished by this study. Enhanced reactivity of the sera in vitro in the presence of AZD1222 could be explained by direct binding of the virus to platelets. Adenovirus binds to platelets and can cause platelet preactivation.

[ Source (thanks monabri) - https://www.researchsquare.com/article/rs-362354/v1 ]

When looking for silver linings after this wretched pub-closing pandemic the acceleration in the development of mRNA vaccine technology would be on my list. Obviously an awful lot of complex science and manufacturing technology was involved in making it work in practice but looking at it in the abstract I find the elegant simplicity very satisfying.

- Julian

It very probably was!

Thanks for providing the relevant extract

- sd

[Bouleversee]

https://ashpublications.org/blood/article/107/7/2766/132046/Thrombophilic-abnormalities-oral-contraceptives

Interesting. My daughter has the Factor II mutation mentioned and she informed her GP practice many years ago, after a consultant suggested all my husband's family and descendants should be tested when his brother nearly died from a pulmonary embolism. No doctor ever raised the question of the OCP with her, however, and she got nowhere when she asked if she could have the Pfizer jab in view of her thrombophilia. Most of the comments in the table were over my head but the conclusion suggests to me that there might well be a connection with the vaccination, especially if those women were on OCP and (possibly even without ever finding out because they had never been tested) also had one or more prothrombin factors. Of course, if they were health workers, they might also already have had the virus and retained antibodies. Since there are alternatives which have not, so far as I am aware, produced this particular consequence, it seems unreasonable to refuse a request for one of them. I should like to know whether one's blood gets thickier/stickier over the years if one has these factors or whether the vires makes it stickier. There was a lot of talk of very sticky blood when Covid patients first started to be hospitalised.

Wouldn't it also make sense for everyone to be tested at birth for these factors along with blood group and anything else of significance and have it prominently on their records with monitoring as necessary rather than find out after an unfortunate event? Older people won't be on OCP but will in some cases have prothrombin factors, as did my husband, and they need to be borne in mind before surgery and medication. I can never understand why check-ups cease at age 70 and one has no GP contact until there is a problem.

[GrahamPlatt]

Reports now starting to filter through of similar (not same) problems with low platelets, bleeds, death from Pfizer & Moderna vaccines; https://onlinelibrary.wiley.com/doi/10.1002/ajh.26132. Mechanism remains speculative.

[Bouleversee]

Reports now starting to filter through of similar (not same) problems with low platelets, bleeds, death from Pfizer & Moderna vaccines; https://onlinelibrary.wiley.com/doi/10.1002/ajh.26132. Mechanism remains speculative.

Many thanks for posting that. Please keep them coming.

So we have the same problems with the Pfizer and Moderna vaccines. I need to read it again carefully to take it all in but at least we can be fairly sure now that these problems are not just coincidental. It will take time to unravel precisely what happens and what the triggers are but it confirms my view that at the very least people with known thrombophilia should have their blood tested before and after being given the vaccine to check platelet levels and also that doctors should know where to send patients if problems do arise. I wouldn't bank on our nearest A&E knowing what to do.

[9873210]

I need to read it again carefully to take it all in but at least we can be fairly sure now that these problems are not just coincidental.

You need to read it. It says coincidental cannot be ruled out.

Thus, the incidence of an immune‐mediated thrombocytopenia post SARS‐CoV‐2 vaccination appears either less than or roughly comparable to what would be seen if the cases were coincidental following vaccination, perhaps enhanced somewhat by heightened surveillance of symptomatic patients. These estimates are very rough so this information should be considered very preliminary. It also assumes that all cases of clinically significant ITP are reported.
...
In summary, we cannot exclude the possibility that the Pfizer and Moderna vaccines have the potential to trigger de novo ITP (including clinically undiagnosed cases), albeit very rarely. Distinguishing vaccine‐induced ITP from coincidental ITP presenting soon after vaccination is impossible at this time. Additional surveillance is needed to determine the true incidence of thrombocytopenia post vaccination.