expert reaction to latest weekly summary of Yellow Card reporting following COVID-19 vaccination published by the MHRA, including updated numbers of CVST and other thrombosis events with low platelets


The latest weekly summary of Yellow Card reporting has been published by the Medicines & Healthcare products Regulatory Agency (MHRA), including updated numbers of cerebral venous sinus thrombosis (CVST) and other thrombosis events with low platelets.


Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“This latest weekly summary of Yellow Card reporting provides some detail on reports to the Medicines and Healthcare products Regulatory Agency (MHRA) relating to clotting events following Coronavirus vaccines.1  The context is one in which some countries (despite assurances from their regulators) have restricted the use of the AstraZeneca coronavirus vaccine, following reports suggesting a possible excess of cases of clotting disorders – in particular, of cerebral sinus venous thrombosis (CSVT) – in people who have received vaccine.  The MHRA report states: “Our rigorous review into the UK reports of rare and specific types of blood clots is ongoing. Up to and including 24 March, we have received 22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets, out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given by that date. There were no reports for the Pfizer/BioNTech vaccine. To note, the current analysis prints include data up to and including the 21 March.

“On the basis of this ongoing review, the benefits of the vaccines against COVID-19 continue to outweigh any risks and you should continue to get your vaccine when invited to do so.”

“CVST is described as:2 “…a rare form of venous thromboembolism (VTE) [which] represents almost 0.5%-3% of all the types of stroke, affecting predominantly younger people with an estimated incidence for adults of 3-4 per million, and for children 7 per million… [It] is characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis.”

“The report found that there were 22 reports of CVST out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given.  That’s about 1.2 cases per million doses given.  Given that the background rate of CVST – at least according to this reference – is one case per 3-4 million adults per year, that is very close to background rates, and is far from being strong evidence of causality.

“It is hard to postulate a mechanism by which a vaccine could cause this particular clotting disorder, but not many other clotting disorders.

“There are many rare conditions, so, just by chance, you would expect to find an excess – more cases than you would expect – for some of them if you compare two large groups of people.

“You only know if there is an excess in adverse incidence reporting, such as the UK Yellow Card system or the US Vaccine Adverse Event Reporting System (VAERS), if you know the background rate of the condition.3  With rare conditions, especially when, like CVST, they are hard to diagnose, this can be a challenge.

“Once a condition becomes associated in people’s minds – regardless of whether the exposure (in this case, vaccination) actually causes the condition – doctors are more likely to look out for the condition in people who’ve had the exposure; and to ask about the exposure in people who have had the condition.  This can cause reporting bias, with the condition being diagnosed or suspected, and reported, in more people who’ve had the vaccine, just because it’s being looked for, and with more assiduous questioning about vaccination in those in whom the condition is diagnosed.  Remember, it is a “difficult diagnosis”, suggesting it may often be missed, and if you look for it more carefully in one group than another, you are likely to find more cases in the group where you look more carefully.

“Once an “alert” has been raised, the only way to be sure if the condition really is more common in people who have been vaccinated, is to do studies designed specifically to study the hypothesis “vaccination causes this condition”.  The studies have to collect or use new data, which usually means they have to be prospective (going forward in time), because otherwise they risk using the data in which the condition was more common, possibly by chance.

“At this point it is impossible to completely rule out the possibility that Coronavirus vaccines might cause CVST.  On the other hand, rates of Covid-19 infections remain common (and are likely to rise, particularly in younger people who haven’t yet been vaccinated, as restrictions are eased); and clotting events are a frequent complication of Covid-19 infection.  Which means that – until and unless Covid-19 rates are brought down much further – the chances of catching it, and getting a clotting event (including CVST) as a consequence of the infection are orders of magnitude more likely than any possible risk of adverse events as a consequence of the vaccine.

“So MHRA’s conclusion that “the benefits of the vaccines against COVID-19 continue to outweigh any risks and you should continue to get your vaccine when invited to do so” is entirely correct.”

1 Medicines and Healthcare products Regulatory Agency (MHRA). Coronavirus vaccine – weekly summary of Yellow Card reporting. MHRA Research and Analysis 2021; Updated 01 Apr 2021; Accessed: 2021 (02 Apr): ( or

2 Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Rafael Moscote-Salazar L. Cerebral sinus venous thrombosis. J Neurosci Rural Pract 2013;4(4):427-438  PMID: 24347950. ( or

3 Vaccine Adverse Event Reporting System. VAERS: Vaccine Adverse Event Reporting System. Vaccine Adverse Event Reporting System (VAERS) web site 2021; Updated [not stated]; Accessed: 2021 (02 Apr): (


Prof Adam Finn, Professor of Paediatrics, University of Bristol, said:

“It’s clear from the level of detail in the many pages of the MHRA weekly analysis print that the UK safety reporting system is extremely thorough.  Given the level of interest and concern around rare serious blood clotting events associated with low platelet counts in several European countries over recent days and weeks, the MHRA report highlights information on such cases among the large number of other diverse events being reported to the UK Yellow Card scheme.  The report states that these cases are being very carefully investigated to better understand whether or not they may have any causal relationship with vaccination.  Nevertheless, the extreme rarity of these events in the context of the many millions of vaccine doses that have been administered means that the risk-benefit decision facing people who are invited to receive COVID19 vaccines is very straight forward: receiving the vaccine is by far the safest choice in terms of minimising individual risk of serious illness or death.”


Prof Sir David Spiegelhalter, Chair, Winton Centre for Risk and Evidence Communication, University of Cambridge, said:

“No medical intervention is ‘safe’, and the balance of benefit to risk is crucial.  The MRHA has now identified 30 serious thrombotic events with low platelets out of 18 million AZ vaccinations, so the average risk of less than 1 in 500,000 is low.

“But it is important to know whether this risk is substantially higher in younger age groups, as has been found elsewhere.  Vaccinating younger people is as much for the wider community as for their direct benefit, and so it is reasonable to try to avoid them causing harm, even if extremely rarely.

“It is vital that the vaccination roll-out is not delayed.  As Sir Patrick Vallance showed last week, even at the current low levels of the virus, a month’s delay in vaccinating 500,000 people between 44-54 would be expected to lead to around 85 severe cases requiring hospitalisation, of which perhaps 5 would die.”


Prof David Werring, Professor of Clinical Neurology, UCL Institute of Neurology, UCL, said:

“Although the number of people diagnosed in the UK with cerebral venous thrombosis after receiving the Astra Zeneca COVID-19 vaccine has increased to 22 cases, this is among 18 million receiving the vaccine.  So the absolute risk of CVST after this vaccine remains extremely low (about 1.5 per million) and it’s not clear if this is any higher than the usual expected incidence of CVST (probably around 5 to 15 per million people per year, though the figures vary as it can be difficult to diagnose in some cases).

“However, emerging evidence suggests that some cases of post-vaccination CVST have unusual features, including low blood platelets, male sex (CVST is typically more common in females), a usually rare type of antibody to platelet-factor 4 (PF-4), and a high risk of severe clots.  This raises the possibility that the vaccine could be a causal factor in these rare and unusual cases of CVST, though we don’t know this yet, so more research is urgently needed.

“CVST can reduce drainage of blood into the cerebral veins, leading to a rare type of stroke.  Common symptoms of CVST include severe, often progressive, headache over hours to days, sometimes with seizures or stroke symptoms (such as weakness of the face, arm or leg, or disturbances of vision or speech).  It is usually treated with the anticoagulant drug heparin, but if anti-PF4 antibodies are present, heparin could make things worse so is not recommended.  Severe CVST can increase pressure inside the skull (often causing drowsiness), which can sometimes be treated with neurosurgery.

“Like most medical interventions, vaccines can have side effects as well as benefits.  The key thing to remember is how rare these brain clots are, and how powerful the proven benefit of vaccination is against COVID.  More research is needed, as it remains uncertain whether the vaccine is causing these unusual CVST.  However, if within a month of receiving the vaccine, a person develops a headache that is severe and of rapid or progressive onset (hours to days), with symptoms of stroke, seizures, drowsiness or confusion then CVST needs to be considered.  Doctors and other health professional need to be aware of the possible link, and know that if the unusual PF4 antibodies are found the usual treatment, heparin, might be hazardous, so should be avoided.  It remains crucial that all suspected new cases of CVST after vaccination continue to be reported to the MHRA through the yellow card system.”



All our previous output on this subject can be seen at this weblink:



Declared interests

Dr Peter English: “No conflicts of interest to declare.”

Prof Adam Finn: “AF is an investigator in trials and studies of several COVID19 vaccines including Oxford-AZ, Pfizer, Janssen and Valneva and advises the UK government and the WHO on COVID19 and other vaccines.  He receives no personal income for this work and is remunerated solely through his employment by the University of Bristol.”

Prof Sir David Spiegelhalter: “No COIs.”

Prof David Werring: “In the last year or so I have received personal fees from Bayer and Portola but am not sure these are directly relevant here. And I work for UCL.”