Australia well positioned to respond to COVID vaccine-induced thrombotic thrombocytopenia

Associate Professor Vivien Chen

Australia has recorded its second case of vaccine-induced immune thrombotic thrombocytopenia (VITT) and clinicians will have a high index of suspicion for the new syndrome associated with the AstraZeneca COVID-19 vaccine.

However the risk of VITT, also known as vaccine induced prothrombotic immune thrombocytopenia (VIPIT), remains extremely low and distinguishing it from other conditions has become the focus for a THANZ vaccine thrombocytopenia working group.

Their advisory statement has become a living guidance document and will be updated on a weekly basis as the international experience – here and here – understanding of the science, and consensus on the terminology changes rapidly.

Associate Professor Vivien Chen, from Concord Hospital and head of the Platelet and Thrombosis Research Laboratory at the ANZAC Research Institute, told the limbic that there had been a fast pivot of local research and diagnostic platforms in order to offer a diagnostic pathway for suspected VITT patients.

“Within Australia, there are a number of thrombosis and haemostasis experts whose work crosses the clinical, the diagnostic laboratory and research into these areas and so there is certainly some depth within the community for looking at this.”

“We have tried to, as rapidly as we can, set up some diagnostic pathways so that we have rapid recognition of the syndrome and the ability to rule in or rule out the syndrome in patients that are presenting.”

She said VITT was quite a specific syndrome, in that it was analogous to autoimmune heparin-induced thrombocytopenia which was different to regular heparin-induced thrombocytopenia (HIT).

She said HIT was also caused by antibodies that recognise platelet antigens PF4 in association with heparin, but the VITT antibody was probably recognising a slightly different target.

“For that reason, some of the tests that we use to screen for HIT are actually negative in VITT. That’s a really important message to get out there,” she said.

Rapid tests such as the Stago STiC, AcuStar, and gel particle assay were not sensitive for detecting VITT.

“Only the HIT ELISA recognises the VITT antibody.”

Associate Professor Chen said some people who are positive in a HIT ELISA do not have HIT.

“And we believe it is going to be the same for VITT – that there are people who are ELISA positive that do not end up having the full syndrome. Thus, similar to our German colleagues, we have added a functional test to our diagnostic algorithm.”

She said the constellation of features and diagnostic criteria for VITT included:

  • thrombosis with a predilection for the cerebral sinus and splanchnic veins that drain the GI tract.
  • the right time frame – currently 4-20 days after vaccine exposure
  • antibody recognised in the HIT ELISA
  • demonstrated activation / hyperactivity of platelets,
  • thrombocytopenia and a significantly raised D-Dimer or thrombocytopenia and low fibrinogen.

And the clinical presentation could be nuanced.

“For example, some patients with cerebral venous sinus thrombosis develop cerebral infarction and secondary haemorrhage as a complication. So patients may present with what appears to be a cerebral haemorrhage but actually the underlying pathophysiology is thrombosis secondary to the VITT syndrome.”

She noted also that just because VITT has only been reported in association with the AstraZeneca vaccine, didn’t mean it didn’t exist in association with other vaccines.

Better outcomes coming

Associate Professor Chen said the case series in the NEJM were being treated at a time when the syndrome was not yet recognised.

“These were the first cases which defined the syndrome and there was mortality associated with it. From our point of view, we are focussed on maximising good outcomes for patients who might exhibit this syndrome. Our international colleagues are expressing confidence that better outcomes will be seen with early recognition and early intervention.”

“If patients meet the entry criteria, then patients need to be treated as if they have VITT until those negative confirmatory tests are available. But as soon as the confirmatory test results are returned and VITT is excluded, then treat down a normal thrombosis pathway.”

Associate Professor Chen, whose lab is currently hosting the confirmatory functional tests for Australia and New Zealand, said the testing was looking very robust for being able to detect VITT.

However not all thrombosis after vaccination is going to be VITT.

“The majority of patients that we have seen in the last few weeks with thrombosis have not been VITT…and it is probable that their thrombosis is just coincidental with the timing of the vaccine.”

“Likewise, thrombocytopenia is not uncommon – sometimes vaccine-associated and sometimes vaccine-independent.”

“And particularly in Phase Ib where there are patients with underlying medical conditions being vaccinated, sometimes the thrombocytopenia will be related to their underlying medical condition and completely unrelated to the vaccine and sometimes it will just be immune thrombocytopenia which is a known immune complication of vaccination.”

While the ATAGI and TGA are responsible for vaccination recommendations, Associate Professor Chen said VITT was a rare but very serious complication.

“But the context is that if we have a COVID outbreak, in patients with severe COVID-19, 1 in 4 will have thrombosis.”

For current sites performing the VITT ELISA and functional testing, see the THANZ testing request form.

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