Thread by @kakape

For the past two weeks, my colleague @GretchenVogel1 and I have been trying to understand what researchers know so far about the rare cases of serious blood clotting observed in people that got the AstraZeneca #covid19 vaccine.

Our story is up here:
sciencemag.org/news/2021/03/c…

@GretchenVogel1 I believe that this is an important story but it is also a complicated one, that is easy to misconstrue. So before you comment or share, please read the whole piece or at least the thread that I‘m gonna attempt later, after I finally get some lunch…
sciencemag.org/news/2021/03/c…

@GretchenVogel1 Okay, let’s do this. Let’s start with caveats:
This is ongoing research. There is a lot we don’t know yet. But as in all things #covid19 we're rapidly learning more.
The paper by Greinacher and others has been submitted to a preprint server but not yet published or peer-reviewed.

@GretchenVogel1 Let’s start with what doctors have actually observed in some AZ vaccinees:
This is not about your garden-variety thromboses. It’s wide-spread clotting with rare thromboses like cerebral venous thromboses coupled with a low platelet count, a very unusual picture.

@GretchenVogel1 Most hematologists will immediately think of disseminated intravascular coagulation DIC (“Verbrauchskoagulopathie” for Germans). That is usually seen in patients with sepsis or severe trauma or sometimes cancer patients. But none of that is the case here.

@GretchenVogel1 That is why doctors started thinking about HIT (heparin-induced thrombocytopenia) which can have a similar clinical picture. It happens in rare cases when patients are given the blood thinner heparin.

@GretchenVogel1 In HIT, heparin builds complexes with platelet factor 4, a platelet protein, and antibodies against these complexes then bind to platelets, other platelets bind to the other end of the antibodies, cross-linking platelets and activating them.

@GretchenVogel1 Greinacher and other scientists think that something similar may be happening here - only without heparin.
The mechanism is still unclear but the researchers we talked to all agreed that the symptoms were so particular that it looked like something real caused by the vaccine.

@GretchenVogel1 So often does this happen?
That is one of the big questions we need clarity on.
Let’s go through some countries:

@GretchenVogel1 1. Norway has vaccinated 130,000 people with AZ and they have seen five such cases, three of whom died.
That's a lot, about one case in 25,000 vaccinees. As @SaraWatle told me, that’s "a high number with a very critical outcome in previously healthy, young individuals”.

@GretchenVogel1 @SaraWatle 2. Germany has vaccinated roughly 2,1 million people with AZ. @PEI_Germany told me that until noon Thursday, 21 cerebral venous thromboses had been reported, incl. 7 deaths.
In 12 cases thrombocytopenia was also reported (it’s not clear for the other cases).

@GretchenVogel1 @SaraWatle @PEI_Germany 3. Then there is the UK, which has given more than 10 million doses of AZ and has reported only 5 such cases. Did they miss cases because they were vaccinating elderly people first? Is something else going on? That will be on thread to follow in next weeks.

@GretchenVogel1 @SaraWatle @PEI_Germany The @BritSocHaem has urged members to be aware of "an important and emerging area of haemostasis and thrombosis practice” and to report any possible cases.
Societies in other countries have done the same.

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem So what are the implications?

Let’s start with the obvious one: If this is indeed a HIT-like mechanism that suggests a potential treatment option, high-dose intravenous immunoglobulins. These unspecific antibodies compete with the anti-PF4 ones and interrupt platelet activation

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem Here is an English-language statement from the German society GTH laying some of this out.
They suggest using IVIG at "a dose of 1 g per kg of body weight daily on two consecutive days” if tests suggest the mechanism is indeed HIT-like.
gth-online.org/wp-content/upl…

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem And what about use of the vaccine?
Some context first:
It’s never just about risks, but the balance of risk and benefit. We know some vaccines have serious, rare side effects like the yellow fever vaccine for instance. We still use them because the benefits outweigh the risks.

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem But with #covid19 the risk of dying is very different for a 75 year old and a 25 year old. And so some countries like France and Finland have made what seems a reasonable choice:
use the AZ vaccine only in the elderly where benefit most clearly outweighs risk.

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem I wouldn’t be surprised at all if more countries follow that model.
As @CiesekSandra told me: "we do not have just one vaccine, we have several. So restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”

@GretchenVogel1 @SaraWatle @PEI_Germany @BritSocHaem @CiesekSandra My big question is where this leaves low- and middle-income countries relying on this vaccine and without the luxury of being able to choose who to vaccinate with what. This may have to be a part of the conversation around #VaccineEquity moving forward.

Looks like @PeterHotez’s thoughts immediately went there as well.

https://twitter.com/peterhotez/status/1375840990418853891

I’ll leave things here for now. There will be more to report in coming days I’m sure. In this pandemic there always is.

Let me add a few ressources here as well
This is an overview of the proposed #VIPIT mechanism and what it might mean from @COVIDSciOntario and starts with a good lay summary:

covid19-sciencetable.ca/wp-content/upl…

And this is the preprint of Greinacher’s paper which finally posted this morning:

researchsquare.com/article/rs-362…