Research based on clinically validated data has confirmed that thrombosis with thrombocytopenia syndrome (TTS) may be induced by COVID-19 vaccination, but that the risks are lower than from SARS-CoV-2 infection.

Data from a UK analysis showed an increased risk of TTS, or vaccine induced thrombocytopenia (VITT), after vaccination, particularly with AstraZeneca’s ChAdOx1, in younger adults, and within 4-27 days after dosing.

While several studies to date have demonstrated increased risks of TTS following the ChAdOx1 vaccination, the data has often been incomplete or at risk of misclassification bias, largely because of inaccuracies in the diagnostic coding of hospital discharge records.

To address this, researchers at the UK Health Security Agency undertook a clinical audit of hospital radiology reports and clinical case notes across four hospital sites in England, to assess the risk of TTS following COVID-19 vaccination with a more accurate dataset.

According to the paper, published in the journal rpth, “case ascertainment was performed manually by clinical haematologists uninformed of vaccination status via a retrospective clinical review of hospital EHR systems”.

The researchers included data on all adults with an acute thrombotic event (venous or arterial thromboembolism) linked with a new-onset thrombocytopenia between January 1 and March 31, 2021. Importantly, platelet counts were gathered for all thrombotic events to ensure accurate identification of TTS.

Cases that were excluded included those with a symptom onset outside of the study timeframe, those identified by the clinician as not having thrombocytopenia at presentation or within 5 days of hospital admission for the thrombotic event, and those with missing NHS numbers.

The final cohort was comprised of 170 individuals (61.4% aged over 65 years old) who had been admitted to hospital for a TTS event with symptom onset or hospitalisation between January 1 and March 31, 2021.

According to the data, 58.2% were not vaccinated at the time of symptom onset, 40% had received a first dose, and 1.8% a second dose. Of those vaccinated, 45% had received BNT162b2 and 54.9% ChAdOx1.

In total, 17 TTS cases occurred 4 -13 days post vaccination with any COVID-19 vaccine, 13 occurred 14-27 days after vaccination, and 14 occurred 28-41 days after vaccination. However, of these, a larger proportion of cases followed vaccination with ChAdOx1 (64.7% 4-13 days after vaccination; 76.9% 14-27 days after; and 57.1% 28-41 days after).

The researchers said they observed non-significant increased risks of TTS in the 4-13 day period post COVID-19 vaccination (relative incidence [RI] 1.65) and in the larger 4-27 day post-exposure period (RI 1.21).

A small and nonsignificant increased risk of TTS was seen following BNT162b2, but only in the 4-13 day period after vaccination (RI 1.46), “and there was an opposite direction of effect (decreased RI of TTS) for all other periods included in the analysis,” they noted.

In contrast, all exposure windows studied for post ChAdOx1 vaccination had RI point estimates above 1, ranging from 1.08 in the 4- to 27-day period, to 1.83 in the 4- to 13-day period), the authors said.

However, greater increased risks of TTS (5.67, 4-27 days post exposure) were observed following ChAdOx1 vaccination in the youngest age group (18- to 39-year-olds), none of whom had received BNT162b2.

Also of note, the data showed that the risk of TTS from infection was SARS-CoV-2 was even higher across all age groups; an almost 5-fold increase in TTS risk was recorded in the 4-27 days after a positive test (RI 4.36), and this was even higher (RI 5.61) in the smaller 4-13 day post exposure window.

While there were key limitations to the study, such as a lack of power, it was the first to use clinician-validated data to assess the potential association between TTS and COVID-19, and its findings “broadly echo those from similar studies” in showing evidence of an increased risk 4-27 days post vaccination, particular with ChAdOx1.

“Our findings suggest that in younger people, an alternative vaccine may be preferable and short-term monitoring of symptoms 4 to 27 days after vaccination are necessary,” they concluded.

Dr Christina Atchison, a Principal Clinical Academic Fellow at Imperial College London and one of the paper’s authors, told the limbic that while the findings won’t have any direct impact on UK practice, “they support the UK Joint Committee on Vaccination and Immunisation (JCVI) advice to the UK Government to offer an alternative vaccine to AZ in unvaccinated adults under 40”.

It remains unknown why younger adults are particularly at risk from the condition post vaccination she added, and, as such, noted that predisposing factors and biological markers of susceptibility will be the next research priorities for TTS, as well as potential new treatments.