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expert reaction to letter presenting three cases of ischaemic stroke following the Oxford-AstraZeneca COVID-19 vaccine

A letter published in the Journal of Neurology Neurosurgery & Psychiatry discusses three cases of ischaemic stroke, blood clots in arteries causing lack of blood supply to part of the brain, reported in young adults after receiving the Oxford–AstraZeneca vaccine.

 

Dr William Whiteley, Reader in Neurology and Consultant Neurologist, University of Edinburgh, said: 

“This paper gives useful insight into three people who had unusual clotting events after vaccination with ChAdOx1 nCoV-19 supporting the existing cases of venous thrombosis associated with arterial occlusion. Fortunately, these are very rare events. Most minor neurological symptoms after vaccination will not be due to a stroke.”

 

Prof Adrian Newland, Professor of Haematology, Queen Mary University of London, said:

“A variety of clotting events have been reported to the MHRA in the period following vaccination with both the Astra Zeneca and the Pfizer vaccines.  These are not confined to the cerebral venous sinus system (CVST) or the abdominal veins (splanchnic vessels) but have also been reported in the arterial system and are often associated with ischaemic strokes.  The syndrome described as Vaccine-induced thrombosis and thrombocytopenia (VITT) has been primarily associated with CVST and has been reported with the Astra Zeneca vaccine.  However, it is not confined to the vessel system and while we do not know why it targets the cerebral sinus system there is no specific reason why, as a generalised activation of clotting, thromboses would not be found elsewhere.  The importance of this report, of only 3 patients, is to emphasise that anyone presenting in the post vaccination period with evidence of clotting should be investigated for VITT as effective treatment significantly reduces the mortality rate.

“It is important to remember that Covid infection is associated with a greater risk of thrombosis with venous thromboembolism occurring in up to 15% and arterial events, including ischaemic stroke, in up to 5%.  These are not generally associated with a reduced platelet count or the development of the autoantibody (PF4) described in VITT.  In the normal population the rate of clotting events is around 1 in 1,000 and with 60 million doses given over such a concentrated period a background rate of clotting events would be expected in those vaccinated and while all will require treatment it is important to identify those with the VITT syndrome as more urgent, and targeted, treatment is required.”

 

Prof Ian Douglas, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“The picture regarding the rare syndrome of blood clots combined with low platelet counts associated with the AZ vaccine is becoming clearer.  Until now, the cases described have tended to involve clots in veins such as cerebral vein thrombosis.  In this series of three case reports, we now have some evidence that the types of blood vessels affected include arteries as well as veins.  It’s important to stress that such cases remain very rare, and it’s certainly much rarer in people who have had the AZ vaccine than it is in people affected by COVID-19 itself.  The description of the cases suggests the patients involved presented with the same kind of symptoms as already described in cases involving cerebral vein thrombosis, and they don’t suggest patients need to be on the alert for anything different.  However, the emergence of details like this will help guide health professionals who may be faced with similar cases in future; the sooner such cases are recognised, the more chance they will quickly receive the right kind of treatment, hopefully leading to better outcomes.”

 

Dr Doug Brown, Chief Executive of the British Society for Immunology said:

“This paper examines three case studies where individuals received the AstraZeneca/Oxford COVID vaccine and later developed ischaemic stroke, which occur when a blood clot blocks the blood flow to the brain.  While these reports can sound worrying, we need to put the risk into perspective and thoroughly review the evidence to work out what the cause is behind these rare reports of stroke – this is what the Medicines Healthcare products Regulatory Agency (MHRA) and Joint Committee on Vaccination & Immunisation (JCVI) will be doing.  They actively monitor all reports of potential side-effects following vaccination and update guidance accordingly with safety always at the forefront of decision-making.  As an example, they recently took a precautionary approach following extremely rare cases of thrombosis and low platelet count to update advice that adults under 40 should receive an alternative to the Oxford/AstraZeneca vaccine where available.

“It is very reassuring that our researchers are working hard to study the COVID-19 vaccine rollout in detail, but we must remember that reports of blood clots following vaccination against COVID-19 appear to be extremely rare.  COVID-19 is a disease that can have serious health consequences in its own right, including the development of stroke in an estimated 1.4% of infections1 – much higher than any potential risk following vaccination.  Vaccination is still the safest and most effective way to protect yourself from falling ill with COVID-19 and we continue to encourage people to accept the offer of both doses of the vaccine.”

1 https://journals.sagepub.com/doi/10.1177/1747493020972922

 

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

“This study reports the findings on just three patients who had a stroke following Covid-19 vaccination.

“With such small numbers, it tells us nothing about whether the vaccine might have caused the strokes.  People – even young people – have strokes; and we don’t always have a neat explanation for the stroke.  It’s tempting to blame something they did shortly before the stroke (in this case the vaccine); but in reality, it’s often something that’s been going on for a long time.

“There are well-established guidance on how to establish a causal link1.

“Even if it is subsequently established that the vaccine can cause adverse events such as a stroke (and as yet we don’t know), strokes and other clotting disorders are very much more common following Covid-19 disease, so if you want to reduce your risk of having a stroke, you are best advised not to get Covid-19, and the best way of doing this remains to be vaccinated.”

  1. World Health Organisation Global Advisory Committee on Vaccine Safety. Causality assessment of adverse events following immunization. Weekly epidemiological record 2001(12):85-89. (https://www.who.int/vaccine_safety/causality/en/ or https://www.who.int/vaccine_safety/committee/reports/wer7612.pdf ).

 

Dr Will Lester, Consultant Haematologist, University Hospitals Birmingham NHS Foundation Trust, said:

“This report does not extend the known clinical spectrum of vaccine-induced thrombosis as ischaemic (arterial) stroke was previously noted in 2 of 23 patients in the paper by Scully et al (NEJM 2021).

“However it does provide more clinical detail with some recommendations for treatment.

“This remains a rare complication and to date, there is no evidence of any increase in ‘normal’ stroke.  Patients with a history of thrombosis, including stroke, should not consider themselves to be at any higher risk of this type of rare thrombosis after vaccination and COVID infection itself is a significant risk for stroke and other types of thrombosis.”

 

Prof Beverley Hunt OBE, Medical Director of Thrombosis UK, and Professor of Thrombosis & Haemostasis, King’s College London, said:

“Vaccine-induced thrombocytopenia and thrombosis is recognised to occur rarely after COVID-19 vaccination.  This case report gives details of three patients who presented with stroke due to arterial clots.  It is well recognised within the UK that VITTs, while it more commonly presents with large vein thromboses, can present in this way and the current guidance documents from the UK Expert Haematology panel and from the College of Emergency Medicine recognise this too.”

 

 

‘Ischaemic stroke as a presenting feature of ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopaenia’ by Talal Al-Mayhani et al. was published in the Journal of Neurology Neurosurgery & Psychiatry at 23:30 UK time on Tuesday 25 May 2021.

DOI: 10.1136/jnnp-2021-326984

 

 

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

www.sciencemediacentre.org/tag/covid-19

 

 

Declared interests

Dr William Whiteley: “University of Edinburgh; University of Oxford, CSO(Senior Fellowship); Stroke Association (UK); European Stroke Organization†; Alzheimer’s Society†; The UK Stroke Association† Chaired meeting at Population Health Research Institute, McMaster University, Canada; medicolegal opinion to UK Courts; Research Oversight Committee, Genome British Columbia; Data Monitoring Committee: INTERACT 3, TEMPO2, XILO-FIST, PAX-D, MOSES, PROTECT-U; Bayer Advisory Board.”

Prof Adrian Newland: “I have no CoI.”

Prof Ian Douglas: “I’ve got grants from and shares in GSK, and I sit on the MHRA’s Pharmacovigilance Expert Advisory Group.”

Dr Doug Brown: “Trustee of the Association of Medical Research Charities.”

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

None others received.

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