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.
Thrombosis with thrombocytopenia (TTS)
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 appears to be higher in younger people. The severity of TTS appears to be higher in younger women. This is why an alternative to AstraZeneca is preferred for people under 60 years of age. The other COVID-19 vaccines are not associated with TTS.
People aged under 60 years can still receive the AstraZeneca vaccine if the benefits outweigh the risks and they provide informed consent.
Symptoms of TTS
Symptoms typically occur between 4 and 42 days after a first dose of the AstraZeneca vaccine.
Symptoms of TTS include:
- severe, persistent headache which does 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 should seek urgent medical attention if they experience any symptoms of TTS.
Rates of TTS
TTS is very rare. In Australia, the rate of TTS is 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.
A range of severity of illness has been reported in Australia. Some cases have been relatively mild, some have had significant morbidity, and some have been fatal.
The overall case fatality rate is lower than reported internationally. This is likely to reflect increased detection due to increased awareness, as well as early diagnosis and treatment.
Risk of TTS
No biological or other risk factors have been identified that predict who will develop TTS.
Cases have been reported in all ages, and in both men and women.
TTS appears to be more severe in younger women.
Almost all reported cases of TTS have occurred after the first dose of AstraZeneca. The risk of TTS is much lower after the second dose.
Who should have AstraZeneca vaccine and who should not
People under the age of 60 years are preferred to have an alternative vaccine to AstraZeneca.
Some people with pre-existing conditions are preferred not to have AstraZeneca for their first or second dose. Find out who should not have AstraZeneca vaccine because of pre-existing conditions.
Advice for health professionals
Heparin treatment and the AstraZeneca vaccine
There is no evidence that exposure to heparin increases the risk of developing TTS.
A patient can be given heparin after AstraZeneca is administered, and vice versa.
Patients with suspected TTS should not be given any heparin or platelet transfusions. These treatments may worsen the clinical course of TTS.
Vaccination after a thromboembolic event
If a patent has had a thromboembolic event, as for any acute illness, delay vaccination until the patient is clinically well.
Allow an interval of at least 1 week before administering the AstraZeneca vaccine to give time for anticoagulation therapy to stabilise.
People who develop CVST or HIT after the first dose of AstraZeneca vaccine
If a patient develops Cerebral Venous Sinus Thrombosis (CVST) or Heparin Induced Thrombocytopenia (HIT) after their first dose of AstraZeneca, do not administer a second dose.
An alternative vaccine is preferred as a second dose for patients who develop CVST or HIT after their first dose of AstraZeneca.
Diagnosis of TTS is challenging in patients who develop HIT, because they may have elevated anti-platelet factor 4 (anti-PF4) antibody levels. Anti-PF4 is also a diagnostic marker of TTS.
If your patient has any symptoms of TTS after vaccination, TTS should be investigated. Initial investigations can occur in primary care in some instances. Suspected TTS cases should be referred to a hospital for further investigation and specialist consultation, including with a haematologist. If the patient is acutely unwell, immediately refer them to an emergency department.
Early detection and management of cases, including referral to hospital, can prevent serious complications developing.
Initial investigations can be performed in a primary care setting if:
- the patient is not acutely unwell, and
- the referring practice can obtain and review the results within 6-hours (contact your local pathology service before sending the patient for blood tests to ensure this).
Immediately refer patients with possible TTS to emergency department if:
- they are acutely unwell (e.g., acute neurological deficit, severe abdominal pain, severe bleeding, or any other concerning symptoms or signs)
- blood tests cannot be performed and reviewed within 6 hours
- they have thrombocytopenia (platelets less than 150 x 109/L) and/or D-dimer ≥5 x upper limit of normal).
We have produced guidance for primary care health professionals, for more information see:
COVID-19 vaccination – Primary care approach to thrombosis with thrombocytopenia syndrome after COVID-19 AstraZeneca vaccine
Guidance on the identification and management of TTS is also available from the Thrombosis and Haemostasis Society of Australia and New Zealand.
Adverse events should be reported to the relevant state or territory health department or to the Therapeutic Goods Administration (TGA). For more information see the TGA website.
Possible presentations of TTS
The sites of thrombosis in reported cases are unusual, varied, and usually venous.
Presentation of thrombosis in TTS include:
- Cerebral venous sinus thrombosis (CVST)
- Thrombosis in the splanchnic (abdominal) circulation
- Pulmonary emboli (PE)
- Deep vein thrombosis (DVT)
- Arterial thrombosis.
In Australia, TTS has presented more commonly as DVT and PE than CVST or splanchnic thrombosis.
Patients may less commonly present initially with signs or symptoms of thrombocytopenia.
Concerning signs or symptoms include:
- headache that persists beyond 48 hours after vaccination, or appears later than 48 hours after vaccination where simple analgesia may alleviate headache initially, but it persists, may be worse when lying down or may be 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 (e.g., 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 investigation required will depend on the clinically suspected site of thrombosis.
Further haematology investigations should be arranged in consultation with a haematologist. This should include ELISA testing for anti-PF4 antibodies. If the ELISA is positive, arrange further functional antibody tests. Patients with suspected TTS should not be given any heparin or platelet transfusions. These treatments may worsen the clinical course.
If TTS is confirmed, management is with a non-heparin anticoagulant and/or intravenous immunoglobulin.
For more information, see: