Vaxzevria (AstraZeneca) vaccine and thrombosis with thrombocytopenia (TTS)

Thrombosis with thrombocytopenia (TTS) is a rare syndrome that occurred in around 2 to 3 people per 100,000 who were vaccinated with AstraZeneca. AstraZeneca is no longer available in Australia from 21 March 2023.

AstraZeneca is no longer available in Australia

There was a link between the AstraZeneca vaccine and a rare but serious side effect called thrombosis with thrombocytopenia syndrome (TTS). 

TTS was very rare. In Australia, the rate of AstraZeneca-related TTS was estimated to be:

  • about 2 per 100,000 people vaccinated with AstraZeneca aged 60 years or older
  • about 2 to 3 per 100,000 people vaccinated with AstraZeneca under 60 years of age.

Symptoms typically occurred between 4 and 42 days after a first dose of the AstraZeneca vaccine.

AstraZeneca is no longer available in Australia from 21 March 2023, so no further cases of AstraZeneca-related TTS can occur in Australia.

On 8 April 2021, the Australian Government received advice and recommendations from the Australian Technical Advisory Group on Immunisation (ATAGI) about the Vaxzevria (AstraZeneca) vaccine and a syndrome called Thrombosis with Thrombocytopenia Syndrome (TTS).

On 17 June 2021, ATAGI issued a statement recommending an alternative to AstraZeneca for those aged under 60 years. 

The following information remains for reference purposes.

Thrombosis with thrombocytopenia syndrome (TTS)

There was a link between the AstraZeneca vaccine and a rare but serious side effect – thrombosis  with thrombocytopenia syndrome (TTS). TTS can cause long-term disability and death. 

TTS involves blood clotting (thrombosis) combined with low platelets (thrombocytopenia). Blood clots can appear in different parts of the body such as the brain or abdomen (belly). TTS is thought to be immune mediated.

The risk of TTS was higher in younger people, so ATAGI preferred  an alternative to AstraZeneca for people under 60 years of age. The other COVID-19 vaccines are not associated with TTS.

People aged under 60 years were able to receive the AstraZeneca vaccine if the benefits outweighed the risks and they provided informed consent, such as during the outbreak of the Delta variant in 2022.

Symptoms of TTS

Symptoms typically occurred between 4 and 42 days after a first dose of the AstraZeneca vaccine.

Symptoms of TTS included:

  • severe, persistent headache that did not improve with regular painkillers
  • blurred vision 
  • confusion or seizure
  • weakness of face or limbs
  • shortness of breath or chest pain
  • severe abdominal (belly) pain
  • leg swelling
  • unexplained pin-prick rash or bruising away from the injection site.

Patients were urged to seek urgent medical attention if they experienced any symptoms of TTS.

Rate of TTS

TTS was very rare. In Australia, the last case of TTS reported by the Therapeutic Goods Administration was in December 2021.1 At that time, the rates of TTS were estimated to be:1

  • about 2 per 100,000 people vaccinated with AstraZeneca aged 60 years or older.
  • about 2 to 3 per 100,000 people vaccinated with AstraZeneca under 60 years of age.

A range of severity of illness was reported in Australia. Some cases were relatively mild, some had significant morbidity, and some were fatal.

The overall case fatality rate in Australia was lower than reported internationally. This was likely due to  increased detection due to increased awareness, as well as early diagnosis and treatment.

Risk of TTS

No biological or other risk factors were identified that predicted who developed TTS.

Cases were reported in all ages, and in both men and women.

TTS appeared to be more severe in younger women.

Almost all reported cases of TTS occurred after the first dose of AstraZeneca. The risk of TTS was much lower after the second dose.

Alternative vaccines

People under the age of 60 years were preferred to have an alternative vaccine to AstraZeneca.

Some people with pre-existing conditions were preferred not to have AstraZeneca for their first or second dose.

Advice for health professionals

Heparin treatment and the AstraZeneca vaccine

There was no evidence that exposure to heparin increased the risk of developing TTS.

A patient could be given heparin after an AstraZeneca vaccine is administered, and vice versa.

Patients with suspected TTS were advised  not to be given any heparin or platelet transfusions. These treatments may have worsened the clinical course of TTS.

Vaccination after a thromboembolic event

If a patient had a thromboembolic event, as for any acute illness, providers were advised to delay vaccination until the patient was clinically well.

Providers were advised to allow an interval of at least 1 week before administering the AstraZeneca vaccine to give time for anticoagulation therapy to stabilise.

People who developed CVST or HIT after first dose of AstraZeneca vaccine

If a patient developed cerebral venous sinus thrombosis (CVST) or heparin-induced thrombocytopenia (HIT) after their first dose of AstraZeneca, providers were advised  not to administer a second dose.

ATAGI preferred an alternative vaccine as a second dose for patients who developed CVST or HIT after their first dose of AstraZeneca.

Diagnosis of TTS was challenging in patients who developed HIT, because they may have elevated anti-platelet factor 4 (anti-PF4) antibody levels. Anti-PF4 is also a diagnostic marker of TTS.

Previously recommended actions

If patients had any symptoms of TTS after vaccination, providers were urged to investigate for TTS . Initial investigations could occur in primary care in some instances. ATAGI recommended that suspected TTS cases be referred to a hospital for further investigation and specialist consultation, including with a haematologist. Providers were advised to refer acutely unwell patients to an emergency department.

Early detection and management of cases, including referral to hospital, could prevent serious complications developing.

Initial investigations could be performed in a primary care setting if:

  • the patient was not acutely unwell, and
  • the referring practice could obtain and review the results within 6 hours .

Providers were advised to immediately refer patients with possible TTS to an emergency department if:

  • they were acutely unwell (for example, acute neurological deficit, severe abdominal pain, severe bleeding, or any other concerning symptoms or signs)
  • blood tests could not be performed and reviewed within 6 hours
  • they had thrombocytopenia (platelets <150 x 109/L) and/or D-dimer ≥5 x upper limit of normal.

ATAGI produced a guidance for primary care health professionals, which has now been archived, as the vaccine is no longer available in Australia.

Guidance on the identification and management of TTS is available from the Thrombosis and Haemostasis Society of Australia and New Zealand.

Adverse events associated with COVID-19 vaccines should be reported to the relevant state or territory health department or to the Therapeutic Goods Administration (TGA).  

Possible presentations of TTS

The sites of thrombosis in reported cases were unusual, varied and usually venous.

Presentations of thrombosis in TTS included:

  • cerebral venous sinus thrombosis (CVST)
  • thrombosis in the splanchnic (abdominal) circulation
  • pulmonary emboli (PE)
  • deep vein thrombosis (DVT)
  • arterial thrombosis.

In Australia, TTS presented more commonly as DVT and PE than CVST or splanchnic thrombosis.

Patients may less commonly have presented initially with signs or symptoms of thrombocytopenia.

Concerning signs or symptoms included:

  • headache that persisted beyond 48 hours after vaccination, or appeared later than 48 hours after vaccination where simple analgesia may alleviate headache initially, but it persisted, may have worsened when lying down or may have been accompanied by nausea and vomiting
  • signs and symptoms of raised intracranial pressure or focal neurological deficits or seizures
  • signs or symptoms suggestive of thrombosis in other anatomical locations (for example, abdominal pain suggestive of thrombosis in the splanchnic circulation, or chest pain suggestive of pulmonary embolism)
  • signs suggestive of clinically significant thrombocytopenia, such as petechial rash or bleeding, or bruising not at the vaccine injection site that cannot be explained.

Assessment and management of TTS after referral to emergency department

The imaging investigations required depended on the clinically suspected site of thrombosis.

Further haematology investigations were advised to  be arranged in consultation with a haematologist. This  included ELISA testing for anti-PF4 antibodies. If the ELISA was positive, providers were advised to arrange further functional antibody tests.

Providers were advised that patients with suspected TTS should not be given any heparin or platelet transfusions. These treatments may have worsened the clinical course.

If TTS was confirmed, management was with a non-heparin anticoagulant and/or intravenous immunoglobulin.

For more information, see:

Injection Technique

Some scientific reports have proposed that inadvertent injection of a COVID-19 vaccine into a blood vessel may have been a contributing cause of serious adverse events following immunisation, such as thrombosis with thrombocytopenia syndrome (TTS) and myocarditis.

ATAGI has reviewed the available evidence and considers that injection technique is highly unlikely to be a contributor to these adverse events for several reasons:

  • The majority of TTS cases occurred after the first dose of a viral vector vaccine (AstraZeneca). The majority of myocarditis cases occur after the second dose of an mRNA vaccine such as Pfizer or Moderna. If intravascular injection was an important contributor, there would not be a differential distribution of cases by vaccine dose.
  • Direct injection into a blood vessel is unlikely in recommended injection sites.
  • TTS typically occurred some days or even weeks after vaccination, which does not fit with the proposed theory of direct vascular injury which occurs early in animal models.

Based on a review of the available evidence, ATAGI does not recommend routinely aspirating (drawing back) needles before injection. This practice was rejected some decades ago, due to several disadvantages including prolonging the procedure, potentially associated pain, and increasing the risk of needle–syringe disconnection.

Further information on vaccine administration is available in the Australian Immunisation Handbook.


  1. Therapeutic Goods Administration (TGA). COVID-19 vaccines weekly safety report: 27 January 2022. Australian Government Department of Health; 2022. (Accessed 9 March 2023).
Date last updated:

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