Thrombosis with thrombocytopenia syndrome (TTS), also known as Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or vaccine-induced immune thrombotic thrombocytopenia (VITT), was a rare syndrome reported in people who received adenoviral vector COVID-19 vaccines such as Vaxzevria (AstraZeneca) and the Johnson & Johnson/Janssen COVID-19 vaccine.

Please note: adenoviral vector COVID-19 vaccines are no longer available for use in Australia. The following information remains for reference purposes.

What is TTS?

The syndrome is characterised by thrombosis formation (blood clots) combined with thrombocytopenia (low platelet count) with symptoms typically presenting in the 4-42 days after vaccination.

According to the Center for Diseases Control (CDC) TTS is classified into 2 tiers based on the location of thrombosis and severity of symptoms. Cases are further classified based on if there has been recent exposure to heparin or not.

Tier 1:

  • uncommon site of thrombosis (eg. brain – cerebral venous sinus thrombosis [CVST] or gut – eg. splanchnic vein, associated with bowel ischaemia and surgery, portal vein or other rare venous and arterial thromboses)
  • may also concurrently have thrombosis in more common locations (eg. deep vein thrombosis or pulmonary embolism)
  • platelet count < 150,000 per microliter
  • positive (+) anti-PF4 ELISA result is supportive, but not required for diagnosis.

Tier 2:

  • common sites of thrombosis such as leg or lungs (eg. venous thromboembolism, deep vein thrombosis, pulmonary embolism)
  • platelet count < 150,000 per microliter
  • positive anti-PF4 ELISA result is required.

Tier 1 tends to be associated with more severe presentations and carries a higher risk of morbidity and mortality than Tier 2. Evidence suggests that Tier 1 is more common in younger age groups.

How did adenoviral vector vaccines trigger TTS?

The exact mechanism of how TTS is triggered is still under investigation, however the majority of cases were associated with the finding of anti-PF4 antibodies. There are no clear diagnostic markers to indicate who is at risk of this syndrome. This is currently under investigation.

TTS appears to be similar to an autoimmune condition known as heparin induced thrombocytopenia (HIT), which is where an immune reaction to the medication heparin impacts platelet function, leading to thrombosis (clots).

The risk of TTS

It is estimated that the risk of developing TTS after dose 1 of Vaxzevria (AstraZeneca) was approximately 2.6 per 100,000 persons, with those under 60 years experiencing more severe outcomes. The risk of developing TTS following dose 2 occurred at a much lower rate.

The risk of developing other clotting disorders after receiving adenviral vector vaccines

There is currently no evidence that adenoviral vector vaccines increase the overall risk of developing other standalone thromboses (eg. other clotting disorders leading to deep vein thromboses, pulmonary emboli, myocardial infarction, stroke) beyond the baseline rate in the general population.

TTS was different to other commonly diagnosed thromboses as it was triggered by an immune response to a specific type of vaccine which then results in the combination of both thrombosis (clots) and thrombocytopenia (low platelet count).

Authors: Daryl Cheng (Paediatricican, Royal Children’s Hospital), Francesca Machingaifa (MVEC Education Nurse Coordinator), Davina Buntsma (MVEC Immunisation Fellow) and Rachael McGuire (MVEC Education Nurse Coordinator)

Reviewed by: Linny Kimly Phuong (Immunisation Consultant, SAEFVIC), Rachael McGuire (MVEC Education Nurse Coordinator) and Hannah Morgan (Epidemiologist, SAEFVIC)

Date: May 2, 2023

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

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