AZ vaccine related thrombosis – when do you suspect?

13th May 2021, Dr Chee L Khoo

Thrombosis with thrombocytopaenia syndrome (TTS)

Thrombosis with thrombocytopaenia syndrome (TTS) has been reported following vaccination with AstraZeneca (AZ) and Johnson and Johnson (JJ) covid-19 vaccines. It is also called VITT (vaccine-induced immune thrombotic syndrome) and VIPIT (vaccine-induced prothrombotic immune thrombocytopenia). It is rare and primarily occurs in those under 50 years old. Although the government recommend that people under 50 years have the Pfizer vaccine, there are people who are in Phase 1A and 1B who can’t and should not wait for the Pfizer vaccine where supplies are limited. If and when they occur, the vast majority of these patients will be presenting to their GP. When do we suspect TTS and how do we diagnosed TTS if we suspect this rare clotting disorder?

The exact pathophysiology of TTS is still unknown however, the vast majority of cases are associated with the presence of antibodies against platelet factor 4 (PF4) or PF4/polyanion complexes. These antibodies are only detectable by specific ELISA methods in specialised laboratories. These clots are not your usual DVT or PEs but clotting in unusual sites such as cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis, or arterial thrombosis, combined with thrombocytopenia.

It is currently estimated that the overall incidence of CVST following the AZ vaccine is around 4 per million first doses administered. Suspected cases have been reported in patients of all ages and genders and currently, no specific predisposing factors have been identified.

TTS should be considered in a patient presenting to primary care between 4 – 28 days after a coronavirus vaccination with any of the following symptoms:

  • New onset of severe headache, which is getting worse and does not respond to simple painkillers
  • Unusual headache which seems worse when lying down or bending over, or may be accompanied by blurred vision, nausea and vomiting, difficulty with speech, weakness, drowsiness or seizures
  • New unexplained pinprick bruising or bleeding shortness of breath, chest pain, leg swelling or persistent abdominal pain

So, if you suspect TTS, how do you confirm or exclude TTS? Pretty simple. If the patient is not acutely unwell, organise an urgent full blood count, D-dimer and fibrinogen. The results should be available the same day to be acted upon then. Patients who are acutely unwell and need urgent attention will referred to your nearest emergency department.

Now, most patients who had the AZ vaccine will have a sore arm for a week and likely will have mild flu-like symptoms for about 1-2 days. They should be well after 1-2 days and if they have any symptoms that may be suspicious of TTS after 4-5 days, then they should see you for assessment and investigations. There will be many with “similar” symptoms as we are in the sinus and flu season and many will present with “suspicious” symptoms but a normal full blood count, d-dimer and fibrinogen may be used to exclude TTS in primary care. It’s that simple.

Let’s not be carried away by the media hype. We are the agent to explain the pros and cons. The general prevalence is about 4 in 1 million AZ vaccines administered. The mortality of TTS is supposed to be 1:4 which translate to a mortality rate of AZ vaccination of 1: 1 million. Timely diagnosis of TTS is life saving. Together we can keep mortality rates low if diagnosed early and appropriate treatment commenced in a timely manner. 

At the end of the day, the decision to go ahead with the AZ vaccine belongs to the patient. We are agents to present the pros and cons in a scientific manner.


UK RCGP: Primary Care Management of Suspected Thromboembolism with Thrombocytopenia after COVID-19 Vaccination