Public policy and personal reticence due to side effects continue to impede the use of Australia’s available and effective AstraZeneca (AZ) COVID-19 vaccine at a time when it is most needed, the now critical 6 months before sufficient supplies of alternate vaccines can deliver the desired 80% vaccination rate required to end the need for crippling lockdowns.
The immediate benefit of a single AZ dose is well understood in the current wave of the delta variant. What is not well understood is a way to reduce the risk in all age groups, further tipping the benefit/risk ratio towards justified, rapid use of every available AZ dose.
At the time of my first dose of AstraZeneca (AZ), COVID-19 vaccine I was not put off in the slightest by the risk of its major complication, the thrombosis thrombocytopenia syndrome (TTS) despite, as a Physician, being very familiar with this serious disorder. This was for two reasons, the first well known; the second, of equal importance, surprisingly absent from public discourse, an important absence I wish to correct here.
The first reason for my confidence in the AZ vaccine was, of course, the extreme rarity of TTS and an overwhelming benefit/risk ratio in my age group.
The second reason was knowledge that the risk of severe disease due to TTS can be all but eliminated by a plan for early detection and treatment with the highly effective combination of intravenous immunoglobulin with an anticoagulant. It is a plan I have applied to myself, family and friends receiving AZ vaccination.
Missing from public discourse is that there are two simple, cheap screening tests for TTS, one or both of which will become abnormal before the onset of serious disease: the d-dimer assay (an early indicator of thrombosis) and a platelet count (thrombocytopenia means low platelet count; TTS is an auto-immune disorder where the vaccine stimulates production of anti-platelet antibodies that both activate the platelets to form clots and result in removal of the platelets from the bloodstream).
The plan to ensure that these tests are carried out, and with expediency, when needed combines personal responsibility of the AZ vaccine recipient with a health system primed to remove avoidable delay.
The first step is for every AZ recipient to be aware of the symptoms to look out for with TTS and to report to a doctor immediately. Which symptoms should trigger this needs to be made very clear.
The Commonwealth Government’s TTS Patient Information Sheet lists: severe, persistent headache (not responding to simple analgesics), blurred vision, difficulty with speech, drowsiness, seizures, chest pain, shortness of breath, swollen leg, persistent belly pain or bleeding into the skin. All of these are essential to respond to, with urgency, but these symptoms occur only after serious intracranial or abdominal clots have already developed and/or the platelet count has dropped from normal at about 250,000 to close to zero.
Minor symptoms can be early warning signs. It is my understanding that almost every person with TTS recalled feeling unwell in the days leading up to life-threatening symptoms. Action at this point, as detailed below, is all but certain to prevent death due to TTS.
The health system’s responsibility lies in providing clear and concise written information on the benefit of early diagnosis of TTS, on the symptoms to look out for and an agreed plan for rapid response.
Access to AZ for people under 60 has required informed consent after discussion of the pros and cons with a GP. It is not an easy line to tread between giving reassurance that TTS is extremely rare on the one hand whilst asking patients to look out for minor symptoms for 6 weeks. But that advice comes with the added reassurance that, if followed, will further reduce, to close to zero, the chance of a life-threatening complication.
The next step is to prime the system for avoidance of delay. At the GP’s discretion, the vaccine recipient could be given a Pathology request form for platelet count and d-dimer assay, marked “Post AZ vaccination, to exclude TTS” with written advice that it can be used if feeling unwell with any new or unusual symptom, however mild, lasting more than a day, 4 to 42 days after vaccination. The vaccinee carries responsibility for informing their GP that they have had the tests performed and, if abnormal, the GP has responsibility for careful follow up or prompt action as appropriate. For the latter, every day lost between first symptom and treatment start represents a system failure.
Such a plan is extremely difficult to implement if the AZ vaccine is administered in a Pharmacy or mass vaccination centre. It is a reason to better resource General Practice where this particular vaccine should be administered, with the TTS risk reduction plan embedded in the discussion for informed consent.
This plan is simple to implement tomorrow by any GP but would benefit greatly by State and Commonwealth Government endorsement and logistic support. It could also be activated by people seeking AZ vaccination who could challenge their GP to provide a pathway to reducing the TTR risk, including expedited access to the screening tests.
The plan varies from current medical practice in two key aspects: facilitating access to pathology tests at the patient’s discretion and advising these tests when any persistent new symptom, however mild, occurs. These are not new concepts in this pandemic; it is, of course, exactly what is done for COVID-19 testing. There could be a lot of normal tests carried out but platelet count and d-dimer assays are very cheap tests, a fraction of the cost of the COVID-19 test, for which hundreds of thousands of negative tests are performed in the public health interest.
It will also place an increased workload on GPs and the Pathology system in ensuring all aspects of the plan work. But this is just for the three months or so before adequate supplies of other vaccines arrive. Perhaps an acceptable impost when the aim is to deliver a first vaccine dose with AZ to as many people and as quickly as possible with the option then of a second dose with an mRNA vaccine if/when available and to encourage those who are due for a second AZ dose to do so.
The need for such rapid action is highlighted by alarming statistics which include: more than 90% of people hospitalised for COVID-19 in the current Sydney wave are yet to receive a single dose of any vaccine; the number of young people, down to teenage, admitted to intensive care; 25% of those over 70 are unvaccinated, awaiting an alternate vaccine. With continuing community spread of the highly contagious and more virulent delta strain, it is time for every line of defense to be activated.
There are two goals in sight. The first, of course, to reduce the risk of serious disease and death from TTS. This has come into closer focus with the increasing number of people under 40 coming forward for AZ vaccination, in large part for the public good. We owe them, in particular, optimised safety. But it should be a priority for all age groups.
The second goal is to increase confidence in the AZ vaccine by better management of the fear of TTS, the cause of AZ resistance.
Could public discussion of minimising risk from TTS enhance anxiety over this rare side effect and further increase AZ vaccine resistance? For some, that is possible.
But for others, it could be a dealmaker. Carrying a blood test form, with control over when to use it, improves autonomy; confidence in an accelerated pathway through the complex medical system, if the tests are abnormal, compounds the feeling of control. Further, not informing people of the option to co-manage their risk with their GP is difficult to justify at several levels.
The starting point is public discussion after which policy can emerge at a pace appropriate to the current parlous state. The human and health service cost of the current delta wave is mounting without an end in sight and the cost, financial and human, of lockdowns, immense.
We will all benefit from a more rapid vaccination programme, delivered with optimised safety. An already very small risk further reduced.
Prof Graeme Stewart retired recently after 40 years as Director of
Clinical Immunology at Westmead Hospital in Sydney with ongoing
contribution to research and teaching. He continues a career-long commitment as an advocate for the public hospital system.
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