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The European Medicines Agency has concluded there is a link between AstraZeneca’s Covid-19 vaccine and “very rare” but dangerous clotting events reported in a number of countries where the vaccine has been used, events which in some cases have been fatal.

A safety committee, the agency said Wednesday, concluded that “unusual blood clots with low blood platelets should be listed as very rare side effects” of the vaccine.

Regulators stressed that the benefits of the vaccine, which was shown to be 76% effective at preventing Covid infections in a large U.S.-based study, still outweigh its risks. “This vaccine has proven to be highly effective to prevent severe disease and hospitalization,” said Emer Cooke, the EMA’s executive director. “And it is saving lives.”

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In a separate briefing, British regulators were more cautious, saying that although there is growing evidence of a link between rare cases of blood clots and the vaccine, further investigation was needed.

The announcements are another blow to the effort to create an affordable and easy-to-administer product envisioned as the backbone of the vaccination campaign in much of the world. Some European countries that had already authorized the vaccine have restricted its use to older populations in an effort to minimize the risk of clotting events; on Wednesday, U.K. regulators said that they would recommend that people under 30 receive other vaccines. Most of the cases of blood clots have occurred have been in people under the age of 60. 

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Disorders caused by blood clots, including heart attacks, vein thromboses, and strokes, are common. But the types of clots that may be linked to the AstraZeneca vaccine are exceedingly rare. They have been marked by low levels of platelets — the blood cell fragments that normally cause clotting. 

The types of clots seen include cerebral venous sinus thrombosis, or CVST, a type of blood clot that occurs in the veins that drain blood from the brain, and a similar condition in the abdomen, known as splanchic vein thrombosis. The clots sometimes occur in combination with bleeding.

The safety committee reviewed 62 cases of cerebral venous sinus thrombosis and 24 cases of splanchnic vein thrombosis reported in the European Union’s drug safety databases as of March 22. Eighteen of these cases were fatal. The cases came from the reporting systems of the European Economic Area and the United Kingdom, where 25 million people had received the vaccine.

The EMA estimated that the rare side effect is being reported in 1 in 100,000 people. The UK’s Medicines and Healthcare products Regulatory Agency, or MHRA, gave a slightly lower figure of one case for every 250,000 vaccinations. Both figures could shift as the data, as well as potential causes, are studied.

From early on, the development of AstraZeneca’s vaccine has been dogged with communications missteps and other problems. But the tie to rare blood clots could have particularly far-reaching implications, both in terms of the vaccine’s use and vaccine hesitancy overall.

The first cases of clotting in people who had been vaccinated were first reported in late February. Since then, a small but growing number of previously healthy people, often women in their 30s and 40s, have developed unusual clotting problems within days of having been vaccinated with the AstraZeneca vaccine.

The adverse events resemble a condition known as heparin-induced thrombocytopenia, or HIT, a rare phenomenon in which people who are given the anti-clotting drug heparin actually develop widely disseminated clotting problems.

In the events that seemed linked to the AstraZeneca vaccine, people developed both a large number of clots and a low platelet count — an unusual combination. The reaction has been dubbed vaccine-induced prothrombotic immune thrombocytopenia by Andreas Greinacher of the University of Greifswald, a German clotting expert.

Greinacher, who reported the phenomenon in a preprint article, has described the condition as treatable.

“We know what to do: how to diagnose it, and how to treat it,” he told reporters last month, according to Science.

Many countries are counting on AstraZeneca’s vaccine. The European Union alone has purchased 400 million doses of the vaccine. The United States has bought 300 million doses of the vaccine, the largest pre-purchase deal of all those contracted by Operation Warp Speed, the vaccine and therapeutics fast-tracking project started during the Trump administration.

Whether it will be used here remains an open question. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told Reuters last week that the U.S. may not need the vaccine.

“My general feeling is that given the contractual relationships that we have with a number of companies, that we have enough vaccine to fulfill all of our needs without invoking AstraZeneca,” Fauci said, without referring to the clotting problem now associated with the vaccine.

AstraZeneca has not yet applied to the Food and Drug Administration for the emergency use authorization that would be needed to deploy the vaccine in the United States, despite the fact that it has been nearly two weeks since the company announced results from the U.S. trial.

“We are currently progressing our EUA submission for AZD1222,” Michele Meixell, senior director of external and executive communications, told STAT on Tuesday. “No further updates right now.”

Regulators say that they will be watching other vaccines, which so far seem to have lower rates of these rare clotting disorders. In particular, the Johnson & Johnson vaccine uses a similar technology to the AstraZeneca one. So far there have been three cases of blood clots associated with low platelets seen with the J&J vaccine, but Peter Arlett, the head of pharmacovigilance at the EMA, said that figure is “extremely small” given the 4.5 million of doses of that vaccine that have been given worldwide. “I think it would be fair to say there is intensive monitoring across the vaccines,” Artlett said.

On a separate conference call with reporters, Adam Finn, a pediatrician at the University of Bristol, said that it would be important to continue to monitor all of the vaccines.

“My fervent hope is that this is a unique problem to one vaccine,” Finn said, “but I also fear that it may not be.”

Correction: A previous version incorrectly described the clots seen with the Johnson & Johnson vaccine.

  • Hi from DC ❤ ✌ 💙. Thx a lot. Very interesting. Basically, new vaccine can’t be perfect.

  • Can we be told how many cases of these rare clots, as found following the AZ vaccine, there might have been in patients ordinarily?

  • As someone with ITP (A blood clotting disorder with low platelets) I’ve carefully watched the manufacture of COVID-19 vaccines. I’ve also gone to the VAERS (Adverse reporting data system) of the FDA in the US.

    I had the option to get Moderna, Pzier or Janssen and chose Janssen. Personally, based on the errors in dosing during the clinical trials, the merging of two data sets used to create a report that looked better was enough for me to question the credibility of this company. Many vaccines are associated with inducing ITP. After all, all vaccines intent is to potentiate immunity through revving up our bodies immune system with some form or ‘live, dead, or genetically modified version of components of the disease that we are trying to eradicate or reduce transmission of. ITP is a form of hyper-immune response. That is why I elected not to get the mRNA vaccines as there is no longitudinal research on this about whether down the road this type of vaccine will be more likely to trigger a life-threatening or lethal hyper-immune response.

  • I am not in the field of medicine. But just want to know, whether any data of those who had this rare clotting problem been collected and analyzed? Any similarity of their DNA, blood group, etc. It should be some combination of different factors.

  • EMA and UK regulators need to be more open and accurate with facts and numbers if they are to obtain the confidence of the public to maintain vaccination roll out. Stating that “most cases occur in under 60 year olds” and “often in 30s and 40s” and then recommending that “people under 30 receive other vaccine” makes no sense! It seems obvious that this vaccine (as of now) should be given only to people over 60.

  • With the strict FDA scrutiny, the AZN deplorable history (of clots, different doses, different efficacies etc all rendering the roll-out of this product terribly mis-managed), and the ample supply / orders of other vaccines, the AZN vaccine will very likely not get an EUA from the FDA. However, having “lent” 4 million AZN doses to Canada and Mexico, the US will have to figure out a way to deal with those upon return, and all the other millions of AZN prior ordered …… Sell them to the EU ?

    • No one can deny that AstraZeneca’s PR is dire.
      But the risk of the most serious adverse reactions from the AZ is around 4 in a million.
      This is based on the most rigorous analysis of over 20 million doses of AZ administered in the U.K.
      By the U.K. MHRA (seen by many as the equal of the FDA) and the JCVI.

      AZ is the ‘workhorse’ vaccine. It’s cheap, and easy to deploy.
      Many poor countries in the world don’t have the luxury of treating vaccines like items on an à la carte menu in a fancy restaurant.

      As for ‘selling it to the EU’?
      If the US doesn’t want the doses of AZ it’s ordered, they can probably be diverted elsewhere.

      BTW
      It’s interesting to compare vaccine prices.
      If one has the imagination to realise this is a GLOBAL crisis (i.e. ‘pandemic’) and abandons all this unhelpful vaccine nationalism, it’s clear that unless another cheap vaccine is released, the AZ is essential.

      Oxford University and AstraZeneca: $2.18 (1.78 euro)
      Johnson & Johnson: $8.50
      Sanofi and Glaxo Smith Klein: $9.27 (7.56 euro)
      Pfizer and BioNTech: $14.71 (12 euro)
      CureVac: $12.26 (10 euro)
      Moderna: $18 euro

  • AZN clots are definitely not exceedingly rare in my world. Of the 3 people that I know who got the first AZN shot, 2 had clots. My 87-year old mother (immediately on blood-thinner injections daily via a nurse coming to her home ). And a 60-year old friend (now in hospital). With pre-existing clotting issues I will absolutely decline this vaccine. There are 3 others approved in Canada – I firmly believe in the benefits of vaccinations – but IMO approval for the AZN Covid vaxx should be revoked as more R&D is needed.

  • So, … 86 cases (cumulatively, for the two syndromes) out of 25,000,000 + people vaccinated. The number of zeroes in this percentage almost overflowed the display on my desk calculator: 0.0000034 , or 0.00034%.
    And how many cases in the non-vaccinated population? Not explicitly stated, one way or the other.
    When people are told that the reactions are “rare,” they think, “Well, ‘rare’ may be 2 or 3 times in 100.” They do not think .00034 times in a hundred. GIVE PEOPLE THE NUMBERS!
    “The experts” are very long on opinion but very stingy with the numerical facts. Is it any wonder that the public feel the “experts” are trying to snow them?

    • Your calculations is correct but in reality in UK, according with NHS website, 2 weeks ago was over 270 deaths related with AZ and around 500 total if you add Pfizer vaccine. Now, even with this number we have the highest numbers of deaths people from entire history related with vaccine campaign. What I’m afraid is that we open a “Pandora box” by lowering safety standards and the consequences for the future will be worst that pandemic.

    • I checked the NHS website, but can’t find anything about 270 AZ deaths, nor 500 total deaths from these vaccins. All I see that these vaccins are very safe.

    • “Chris,” above, cites these numbers for the U.K.
      “But the risk of the most serious adverse reactions from the AZ is around 4 in a million. This is based on the most rigorous analysis of over 20 million doses of AZ administered in the U.K. By the U.K. MHRA (seen by many as the equal of the FDA) and the JCVI.”

      Do you have another, better source? If so, please cite.

  • In today’s MHRA/JCVI (UK agencies) briefing on the AstraZeneca vaccine it was announced that by the end of March over 20 million doses of AZ have been administered.

    Statistical analysis shows the following.

    Those aged 60-69 have a 14.1 in 100,000 risk of being admitted to a hospital ICU if they develop Covid-19.
    This age group has a 0.2 in 100,00 risk of ‘serious harm’ from the AstraZeneca vaccine.

    There doesn’t seem to be data on the over-69s as, in the UK, this age group were given the Pfizer/BioNTech vaccine as this vaccine was approved well before the AstraZenica.

    It’s logical to expect your risk of being hospitalised with Covid-19 would be considerably higher, given your age. (77 years)
    You could use the following to calculate that risk.

    https://www.qcovid.org/Calculation

    Human beings are notoriously bad at assessing personal risk. And most people have little or no expertise when it comes to assessing risk by interrogation of data.
    Understanding ‘absolute’ and ‘relative’ risk is crucial.

    Only you can decide what’s best for your health and well-being. But you should make decisions based on informed opinions and expert advice.

    Vi auguro ogni bene

  • The biological mechanism for this type adverse event must be investigated and discovered.
    In the meantime, in addition to the demographic associations already discovered, associations with other disease conditions and other medications or supplements must be sought.

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