GPs should do blood tests for non-acute patients who are suspected of having the rare blood clotting condition associated with the Astra Zeneca Covid vaccine, NICE has said.
The guideline, published today, also said that GPs could undertake regular blood tests for confirmed patients after discharge from hospital as part of their ongoing management.
The extremely rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) – with only 14.2 cases occurring per million doses of Covid vaccine – was first identified in March 2021 in relation to Covid vaccinations.
In its rapid guideline, NICE said that those suspected of having VITT who are ‘acutely unwell’ should be referred to the emergency department ‘immediately’.
However, it added that a full blood count should be performed in primary care if the patient is not acutely unwell and results can be obtained and reviewed on the same day.
NICE said: ‘The panel noted that rapid turnaround testing for thrombocytopenia in primary care, if available, could help to avoid unnecessary referrals to emergency departments. However, if blood tests showed thrombocytopenia, the panel agreed that same-day referral to secondary care for further investigations was appropriate.’
Those with a low platelet count should be referred to the emergency department ‘immediately’, it added.
If blood tests indicate the person is unlikely to have VITT but a ‘high clinical suspicion’ remains, GPs should consider repeating the full blood count after two or three days or if symptoms worsen, or discuss further tests with a haematologist, it said.
Healthcare staff should also discuss the signs and symptoms of VITT with those deemed unlikely to have it after blood tests and provide advice on when and where to seek further help if symptoms persist or worsen, it said.
They should think about ‘alternative diagnoses’ such as headaches or venous thromboembolic diseases for patients whose blood tests indicate it unlikely that they have VITT, it added.
NICE said the new or ongoing symptoms of VITT GPs should look out for in those presenting within five and 30 days of having a Covid jab are:
- new onset of ‘severe’ headache, which is getting worse and does not respond to simple painkillers
- an ‘unusual’ headache that seems worse when lying down or bending over, or may be accompanied by blurred vision, nausea and vomiting, difficulty with speech, weakness, drowsiness or seizures
- new unexplained pinprick bruising or bleeding
- shortness of breath, chest pain, leg swelling or persistent abdominal pain.
Patients diagnosed with VITT may be treated with non-heparin anticoagulants and surgical interventions to treat thrombosis in secondary care, NICE recommended.
It added that GPs could monitor VITT patients discharged from hospital with blood tests done every two to three days for the first two weeks following discharge, then monthly for the first six months and then every three months if no relapses occur.
It said: ‘Monitoring of D-dimer, fibrinogen and platelets is generally done in secondary care, but blood tests could be done in primary care.
‘If the person with VITT prefers monitoring in primary care, ensure that both the person’s GP and their local haematology service are aware that the person’s haematology department is responsible for interpreting blood test results and making treatment decisions.’
Meanwhile, NICE added that referral for psychological support should be considered for VITT patients, although it said that some ‘may have their psychological needs met by good communication and information provision, particularly when interacting with primary care services’.
The guideline said: ‘VITT is a disorder that only occurs in the context of vaccination, which people have to protect their health and that of the population.
‘In the panel’s experience, VITT mainly affects people who are previously fit and healthy, but now have an ongoing potentially life-threatening medical condition. People with VITT may therefore have lost confidence in vaccination, which is a notable psychological challenge to be addressed.’
There is ‘limited evidence available’ because VITT is a new condition, but NICE is ‘continually monitoring’ the evidence and will update its recommendations ‘frequently’, it added.
Dr Paul Chrisp, director of NICE’s Centre for Guidelines, said: ‘This is a living guideline, which can be continuously updated to incorporate the latest evidence and keep abreast of new developments.
‘This guideline has not looked at the safety of Covid-19 vaccines; that is not NICE’s remit and the data from the MHRA shows the benefits of Covid vaccines far outweigh the risks. NICE’s role here is to provide the best advice to help clinicians treat patients in the rare instances where they do develop VITT.’
Following reports of rate blood clotting events related to the AstraZeneca vaccine in March, a large number of European countries have restricted its use.
In the UK, it was announced in May that GP practices should offer patients under 40 an alternative to the AstraZeneca vaccine amid blood clot fears, following similar guidance for other age groups.
The MHRA has advised that vaccinated individuals should ‘seek immediate medical attention if four or more days after vaccination they develop new-onset or worsening severe or persistent headaches with blurred vision, which do not respond to simple painkillers’.
NICE VITT recommendations
3 – Identifying suspected VITT
For people presenting to primary care or emergency care, or contacting NHS 111 with new or ongoing symptoms within 5 to 30 days of having had a COVID-19 vaccination, follow the advice from Public Health England on:
- recognising signs and symptoms of thrombocytopenia or thrombosis
- what to do if you suspect a case (this covers referral and reporting).
The signs and symptoms listed by Public Health England (accessed 06 July 2021) are as follows:
- new onset of severe headache, which is getting worse and does not respond to simple painkillers
- an unusual headache which seems worse when lying down or bending over, or may be accompanied by blurred vision, nausea and vomiting, difficulty with speech, weakness, drowsiness or seizures
- new unexplained pinprick bruising or bleeding
- shortness of breath, chest pain, leg swelling or persistent abdominal pain.
The panel discussed the advice published by Public Health England on symptoms, referral and reporting was helpful, and agreed that it should be linked to from the guidance and the list of symptoms reproduced for ease of use. In the panel’s experience, symptoms are likely to develop slightly later than reported by Public Health England, so the period of time specified in the recommendation is based on consensus.
4 – Investigations and diagnosis
When assessing people with suspected VITT, ask about their vaccination history, take into account their overall clinical condition, and:
- refer people who are acutely unwell to the emergency department immediately, or
- perform initial tests (full blood count) in primary care if:
- the person is not acutely unwell, and
- same day test results can be obtained, and if they show thrombocytopenia, the person can be referred to the emergency department immediately.
The panel agreed that urgent referral was needed for people who are acutely unwell, because VITT is a potentially life-threatening condition and prompt treatment is important. However, VITT remains rare, meaning that initial assessments need to balance the risk of missing a case against the possibility of conducting unnecessary investigations. The panel discussed the possibility of over-referral, which could potentially lead to exceeding the capacity of emergency departments. However, the panel broadly agreed that people with symptoms of suspected VITT often present to the most appropriate service anyway (that is, people presenting in primary care tend to be less acutely unwell, and people who are acutely unwell tend to present to emergency care), so the risk of over-referral may be minimal. The panel noted that rapid turnaround testing for thrombocytopenia in primary care, if available, could help to avoid unnecessary referrals to emergency departments. However, if blood tests showed thrombocytopenia, the panel agreed that same-day referral to secondary care for further investigations was appropriate.
4.2 – Further care when VITT is unlikely
For people whose blood tests indicate it is unlikely they have VITT:
- think about alternative diagnoses and manage in line with the relevant NICE guideline, for example:
- tell them that it is unlikely they have VITT. Discuss the signs and symptoms of VITT, and when and where to seek further medical attention if their symptoms persist or worsen.
If a high clinical suspicion of VITT remains, consider:
- repeating the full blood count after 2 to 3 days or if symptoms worsen, or
- discuss the need for further investigations with a clinical haematologist.
The expert advisory panel noted that, in their experience, an estimated 5% of people with VITT did not have thrombocytopenia at presentation. Therefore, if thrombocytopenia is not seen but a strong clinical suspicion of VITT remains, a repeat platelet count may be justified.
The panel agreed that if VITT was unlikely, it was important to investigate possible thrombosis (as indicated by the person’s signs and symptoms at presentation), or think about alternative causes of the person’s symptoms.
The panel acknowledged that most cases of acute thrombosis are unlikely to be associated with VITT, even in the context of a relevant vaccination history. However, the panel acknowledged that if a person’s symptoms worsen they should seek further medical advice.
Further investigation for VITT may sometimes be prudent because some people with confirmed VITT do not have thrombocytopenia when they first seek medical attention, but it develops later. The panel agreed that it was important for clinicians to recognise that an initial normal platelet count would not fully exclude VITT. However, they appreciated the need to balance avoiding missing cases against the small number of people who may have VITT but no thrombocytopenia at initial testing.
6 – Ongoing management
6.1 – Patient-centred care
Consider referral for psychological support for people who have, or have had, VITT. Take into account that family members and carers of people with VITT may also benefit from psychological support, particularly if the person has been seriously ill, and give them information on available support services.
Thrombosis UK has produced patient information and support for people with VITT.
The panel highlighted that people with VITT may have need of psychological support, even if they did not have clinically-diagnosed anxiety or post-traumatic stress disorder. VITT is a disorder that only occurs in the context of vaccination, which people have to protect their health and that of the population. In the panel’s experience, VITT mainly affects people who are previously fit and healthy, but now have an ongoing potentially life-threatening medical condition. People with VITT may therefore have lost confidence in vaccination, which is a notable psychological challenge to be addressed.
The panel noted that people with VITT may have differing levels of support needs and that this may be related to the severity of their condition. Post-intensive care syndrome is a recognised condition, meaning that people with VITT who need treatment in intensive care may have higher psychological support needs than other people with VITT. However, some people with VITT may have their psychological needs met by good communication and information provision, particularly when interacting with primary care services.
The panel’s experience indicated that psychological support services were not always made available to people with VITT. The panel agreed that making a recommendation about psychological support was important to improve practice in this area. The psychological needs of family members and carers of people with VITT were also recognised as important by the panel.
6.2 – Monitoring response and treating relapse
After discharge from hospital, keep the person under the care of the haematology department and assess symptoms and monitor as follows:
- measure D-dimer, fibrinogen and platelet counts every 2 to 3 days for the first 2 weeks
- repeat ELISA for platelet factor 4 antibodies weekly for the first 4 weeks
- after the initial periods noted above, repeat monitoring tests monthly for the first 6 months and, if no relapses occur, reduce the frequency of testing to every 3 months.
When platelet 4 antibodies are no longer detected, review the need for ongoing treatment and monitoring.
Monitoring of platelet factor 4 antibodies is done by secondary care services.
Monitoring of D-dimer, fibrinogen and platelets is generally done in secondary care, but blood tests could be done in primary care. If the person with VITT prefers monitoring in primary care, ensure that both the person’s GP and their local haematology service are aware that the person’s haematology department are responsible for interpreting blood test results and making treatment decisions.
The panel discussed that the natural history of VITT is still not well understood, with little published evidence available, so based the recommendations on monitoring on their experience of treating people with VITT. They noted that relapses after initial response to treatment can happen quickly, meaning that intensive monitoring is advisable in the first weeks after diagnosis. Most people with VITT continue to have platelet factor 4 antibodies after discharge from hospital, and the panel expected that monitoring would need to continue until these antibodies were no longer detected. If no relapses were detected after 6 months, the panel agreed that reducing the frequency of monitoring to every 3 months would be justified.
The panel discussed the need for monitoring to be managed by clinical haematologists. It was acknowledged that some people with VITT might not be able to attend hospital for all monitoring. In these circumstances, blood samples could be taken in primary care but the responsibility for interpreting those results and making treatment decisions would remain with the haematology department.