An interesting editorial in The Lancet Haematology published May 2021 explores this issue.
COVID-19 vaccines are being rolled out globally, yet the AstraZeneca vaccine still continues to be marred with controversy.
This varies from its slow and still awaited approval by the US Food and Drug Administration amid the concerns about the lack of large scale trial data from the USA, to safety alerts around the development of rare blood clotting events. This couples with thrombocytopaenia which is low platelets, particularly central venous sinus thrombosis, CVST and splanchnic vein thrombosis, SVT.
As of April 4th 2021, 169 cases of CVST and 53 cases of SVT have been reported in the EEC and the UK after administration of over 34 million vaccines.
On April 7th 2021, the EMA, the European Medicines Agency and the UK’s Medicines and Healthcare products Regulatory Agency, MHRA updated their guidance with the EMA recommending that these thrombotic events be listed as very rare side effects in the product information.
They requesting new studies and amendments to ongoing studies to provide more information on these rare events, and the UK advising that people younger than 30 years should be offered an alternative to the AstraZeneca vaccine if available.
However, both regulators made it clear that in the vast majority of people, the benefits of the vaccine outweighed the risks of the side effects.
The exact cause and nature of these thrombotic events is still unclear – although they have been likened to heparin–induced thrombocytopaenia HIT triggered by the immune response and also termed vaccine induced prothrombotic immune thrombocytopaenia.
Regulators and societies have published guidance on how to diagnose and treat HIT after vaccination.
This includes alerting vaccine recipients to seek medical assistance immediately if they have side effects such as dizziness, headache and visual disturbance occurring more than three days after vaccination.
Several European countries halted or changed the age limit for the AstraZeneca vaccine, guidance from regulators is welcome to avoid further erosion of public trust and to ensure the coordinated rollout of vaccines.
Flexibility in policies and quick actions from regulatory agencies and governments, such as the rear distribution of Pfizer vaccines from EU countries to other countries in the union that only have the AstraZeneca vaccine available that are now experiencing delays in delivery that authors argue are needed to maximise the efficiency of the rollout.
Although more women than men are reported to have had these thrombotic events.
The MRHA and EMA have not highlighted any significant risk factors such as age and sex because the data is limited for any robust estimate to be made.
A known risk factor for CVST is the use of oestrogen containing oral contraceptives and pregnancy, with an estimated incidence of 2.78 per 100,000 person years in women aged 31-50 years, compared with 1.32 overall, according to data from two Dutch provinces.
The editor argues that continued publication of age and sex disaggregated data for the incidence of CVST in both vaccinated and unvaccinated populations is important to help guide the assessments of people’s individual risk factors for these rare events.
The discussion around the safety of the vaccine also raises the point of what is an acceptable amount of risk for any intervention.
Women have lived with the increased risk of CVST as a result of taking oestrogen–containing oral contraceptives for many years and ensuring that patients are informed of such risks is vital regardless of any intervention.
For the AstraZeneca vaccine, transparent and clear communication of the ongoing assessments of the risks is needed the editor argues to ensure that public trust is not eroded further.
A YouGov poll involving nearly 9,000 Europeans in mid-March 2021 suggested that people in France, Germany, Spain and Italy are more likely to see the AstraZeneca vaccine as unsafe rather than safe.
Continued surveillance will provide stronger evidence on the possible link between rare thrombotic events and the AstraZeneca vaccine.
Risk benefit assessments for different age groups need to be defined as safety data on rare events emerge.
What is clear is the evidence for the benefits of all the approved COVID-19 vaccines, including AstraZeneca, for preventing serious COVID-19 are helping nations control the disease.
The editor continues to argue that as the pandemic continues, the enormous undertaking of vaccinating billions of people around the world still poses one of the biggest challenges.
Transparent reporting of safety is vital to ensure that the public trust in the vaccination programme is improved and maintained, as we continue with one of the largest global vaccination programmes ever undertaken.
The London General Practice, as one of the leading London doctors’ clinics in London provides a full COVID testing service and is proud that the Government has achieved such marvellous results with its vaccination programme.
The London General Practice commends the Government and as a London doctors’ clinic recommends all those who are eligible for COVID vaccination to be vaccinated.
Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed