Dr Toni Hazell assesses the MHRA warning about persistent headache after the AstraZeneca vaccine
NOTE: This article was updated on 21 April 2021 at 17:00
It was all going so well in the UK vaccine rollout – by the end of February we were vaccinating more than 300,000 people a day,1 with cautious optimism on lifting restrictions over the next few months. Now, a number of European countries have suspended use of the AstraZeneca (AZ) vaccine over concerns about an increased risk of thrombosis2 and the UK Medicines and Healthcare products Regulatory Agency (MHRA) has recommended anyone under the age of 30 be given an alternate vaccine. This article takes you through the issues.
The vaccine’s benefits significantly outweigh risks, but the risk-benefit balance changes with age
1. As of 5 April, there had been 22 fatalities in the UK linked to thrombosis after the AZ vaccine.3 This should be seen in the context of more than 20 million doses of this vaccination having been given so far. It is estimated that the vaccine programme has prevented at least 6,100 deaths in adults aged over 70, but the thrombotic adverse effect seems disproportionately to affect younger adults. This changes the risk-benefit analysis, so for those aged under 30 who are receiving the vaccine despite having no medical co-morbidities, it is preferable to offer an alternative vaccine, such as Pfizer or Moderna, if available. This group will currently largely be health and social care professionals, unpaid carers or the household contacts of immunocompromised patients.
The JCVI statement4 is not explicit on what to do if no alternative is available, but it would seem reasonable for the person to make an informed decision on whether to have the AZ vaccine in order to be vaccinated sooner, or wait for an alternative. For those being vaccinated due to an underlying health condition, the JCVI advises that the benefits of prompt vaccination with the AZ vaccine ‘far outweigh the risk of adverse events’. Advice is being finalised for the under-30s when the vaccine programme reaches the next stage and they are offered a vaccine based on age alone. Those who have already had a first AZ jab should have the same vaccine when their second dose is due.
The MHRA alert concerns cerebral sinus vein thrombosis (CSVT) with thrombocytopenia
2. CSVT is a rare event, with an incidence of 3-4 per million adults per year.5,6 According to the MHRA, by April 5 there had been 50 cases in the UK associated with thrombocytopenia following the AZ vaccine. This is less than five per million people vaccinated.3 The MHRA recently confirmed ‘the evidence to date does not suggest that the AstraZeneca Covid-19 vaccine causes venous thromboembolism without a low platelet count’. This may be helpful for patients seen in primary care early in the day, where a same-day FBC may plausibly be arranged.
Anyone with onset of headache four or more days after having the vaccine is advised to seek medical attention
3. The MHRA has said that ‘as a precautionary measure, anyone who has symptoms four days or more after vaccination is advised to seek medical attention’.3 The symptoms that should prompt concern are a new-onset severe and persistent headache, blurred vision, confusion, seizures, shortness of breath, chest pain, leg swelling, persistent abdominal pain, unusual skin bruising or pinpoint spots beyond the injection site.3 Realistically, most people in this situation will present to their GP, where they will be triaged by phone or electronic consultation to see if they need a face-to-face appointment.
CSVT can only be diagnosed by imaging modalities that are not available in primary care
4. A firm diagnosis of CSVT can only be made in secondary care, as it requires CT or MRI venography, or cerebral angiography. Bloods and a lumbar puncture may also be done. It is therefore logical to say anyone with a post-vaccination headache should present to the emergency department, rather than their GP. However, while we can’t do fancy tests, we can take a good history, and history is 80% of diagnosis.6 So, the question is, do we send these patients straight to secondary care, or can we have useful input into the care of a patient with a post-vaccination headache?
Consider the risk factors for CSVT
5. The MHRA said on 7 April that the evidence of a link between CSVT and the AZ vaccine was ‘stronger’ than originally thought.7 CSVT usually occurs in conjunction with at least one other risk factor. These may include systemic conditions such as vasculitis or thrombophilia, cerebral or systemic infections, trauma, malignancy, obesity, thyroid disease and inflammatory bowel disease. It would therefore be sensible to enquire about these conditions, because their presence might lower your threshold for referral. However, the British Society of Haematology has raised concerns that vaccine-associated CSVT is being seen in patients with no risk factors, so their absence should not provide false reassurance.
Risk factors for CVST include prothrombotic conditions, infections, mechanical trauma, vasculitis, intracranial defects, haematological diseases, systemic diseases and drugs.7 A description of each of these risk factors can be found at https://www.karger.com/Article/Pdf/509802
Know your headache red flags
6. When seeing any patient with a headache, we should always be aware of the features that might indicate a serious cause, and should make us consider referral. These include:9
- Sudden-onset severe headache, reaching maximum intensity within five minutes.
- New-onset headache in a person aged over 50 (consider temporal arteritis or a space-occupying lesion).
- A headache that progressively worsens or whose character changes dramatically.
- Associated features such as fever, seizure, neck stiffness, papilloedema, neurological deficit, personality change, dizziness, visual disturbance or vomiting.
- An atypical aura, or an aura occurring for the first time in a woman who uses a combined contraceptive method.
- A whole household with new headache – consider carbon monoxide poisoning.
- Immunocompromised due to unmanaged HIV, a primary immunodeficiency or the use of immunosuppressant drugs.
- Current or past malignancy – consider cerebral metastases.
Don’t forget your usual decision-making matrix for headaches
7. When a patient leaves your room (or your virtual phone or video consulting room), it is comforting to have some idea of a diagnosis.
This doesn’t always happen in general practice – many patients present with nebulous symptoms that take time to unpick. But I would feel more comfortable reassuring a patient with a headache after vaccination if I can give them a plausible reason for their headache.
Does it fit with a flare of pre-existing migraine, tension headache or something else already known? Or is there another reason to be concerned? Meningitis, mastoiditis, intracranial bleeds and tumours haven’t gone away just because we’re all thinking about CSVT. If you can’t fit this headache to any diagnosis, and it has started after vaccination, then your GP antennae might start to twitch. Be aware that lateral sinus involvement can mimic middle-ear and mastoid infection, with features such as fever, discharge and pain over the mastoid process.
CSVT often, but not always, presents with a worrying headache
8. CSVT headache usually has features of raised intracranial pressure – it is generalised, progressive and worsens on lying down or straining.
Some patients may have a ‘thunderclap’ headache, traditionally described as like being hit on the back of the head with a hammer. If this happens, your next decision is easy – whether or not they are at risk of CSVT, they need to be referred to rule out a subarachnoid haemorrhage. However, some patients with CSVT will present with just an isolated headache, so the absence of features of raised intracranial pressure can’t fully rule out CSVT.
Abnormalities of eye movements should make you concerned
9. Patients with CSVT may have involvement of the oculomotor, abducens or trochlear nerves, so any weakness or paralysis of eye movement should raise a red flag for hospital review. Other known symptoms include seizures and focal deficits such as hemiparesis, which you would usually associate with a stroke.
Know what your local pathways are for patients with a post-Covid vaccine headache
10. This is a new issue for general practice and advice is rapidly changing. Patients have been advised to seek urgent medical advice if they experience any of the symptoms listed in the box below between four and 28 days after a coronavirus vaccination. Advice from Public Health England10 goes on to say: ‘If you have clinical concern, patients should be urgently referred to hospital and to appropriate specialist services for further assessment, particularly if the symptoms are unexpected and present in combination with thrombocytopenia.’ Advice to do an urgent FBC has been withdrawn, probably because primary care access to same-day results is limited. Specific pathways have been developed for this issue in some areas. These may involve the medical team assessing the patient in an ambulatory care unit or similar, sometimes with the help of a D-dimer, followed by a decision on whether to scan, based on the hospital’s protocol. Find out your area’s arrangements before you need them. Medicine is an art and not a science and different GPs are likely to have their own thresholds both for face-to-face review and for hospital referral.
This information was correct as of 21 April 2021
Dr Toni Hazell is a GP in north London
MHRA advice to patients
|If you experience any of the following from around four days after vaccination, you should seek urgent medical advice:|
•Severe headache that is not relieved by simple painkillers or is getting worse, or feels worse if you lie
down or bend over
• An unusual headache that may be accompanied by blurred vision, confusion, difficulty with speech, weakness, drowsiness or seizures (fits)
• A rash that looks like small bruises or bleeding under the skin beyond the injection site
• Shortness of breath, chest pain, leg swelling or persistent abdominal (tummy) pain
|Red flags for post vaccine thrombosis10|
• New onset of severe headache, which is getting worse and does not respond to simple painkillers
• An unusual headache that is worse when lying or bending down, or accompanied by blurred vision, nausea and vomiting, difficulty with speech, weakness, drowsiness or seizures
• New onset of unexplained pinprick bruising or bleeding
• Shortness of breath, chest pain, leg swelling or persistent abdominal pain
- Public Health England. Vaccinationsin the UK. 2021. coronavirus.data.gov.uk/details/vaccinations
- Wise J. Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. BMJ 2021;372:699
- Coronavirus vaccine – weekly summary of Yellow Card reporting, April 15. tinyurl.com/april15-yellow-card
- JCVI statement on use of the AstraZeneca COVID-19 vaccine: 7 April 2021, tinyurl.com/JCVI7April
- Alvis-Miranda H, et al. Cerebral sinus venous thrombosis. J Neurosci Rural Pract 2013;4:427-38. tinyurl.com/Alvis-CSVT.
- Martinelli I, et al. Cerebral sinus-venous thrombosis. Intern Emerg Med 2012;7:S221-5
- Cooke G. A is for Aphorism. Is it true that ‘a careful history will lead to the diagnosis 80% of the time’? Australian Family Physician, 2012; 41 (7):449-544 . tinyurl.com/Cooke-AFP
- MHRA issues new advice, concluding a possible link between COVID-19 Vaccine AstraZeneca and extremely rare, unlikely to occur blood clots, tinyurl.com/AZ-headache-April
- Idiculla S, et al. Cerebral Venous Thrombosis: A Comprehensive Review. Eur Neurol 2020;83:369-79.
- NICE. Scenario: Headache – diagnosis. October, 2019. tinyurl.com/NICE-CKS-headache
- PHE. Information for healthcare professionals on blood clotting following COVID-19 vaccination. 2021. gov.uk/government/publications/covid-19-vaccination-blood-clotting-information-for-healthcare-professionals/information-for-healthcare-professionals-on-blood-clotting-following-covid-19-vaccination