(340) Epidemiology of Thrombotic Thrombocytopenia Syndrome before, during and post COVID-19 pandemic: English sentinel network cohort studies

Background: A very rare and serious condition comprising the co-occurrence of thrombosis and thrombocytopenia was seen in early 2021 after vaccination with AZD1222 (ChAdOx1 nCoV-19). Previous studies on this condition were limited by low cases and relied on only primary or secondary care data

Objectives: To estimate thrombotic thrombocytopenia syndrome (TTS) rates pre, during, and post-COVID-19 pandemic, describe patients’ characteristics, and identify risk factors.

Methods: We used the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) database of routinely collected primary care data for 18M people in England, linked to national vaccination, laboratory tests, hospitalisation, and death records.
All individuals aged 16+ years with >1 year enrolment in ORCHID were included. Three study cohorts were examined:
Pre-COVID-19 cohort: 1/1/2011–31/12/2019.
COVID-19 cohort: Those with confirmed COVID-19 disease (diagnostic code & positive PCR +/-10 days) between 1/7/2020–31/12/2020.
COVID-19 vaccination cohort: Those with AZD1222 (ChAdOx1 nCoV-19) vaccination between 1/1/2021–4/7/2022.
As codes for TTS are unavailable, TTS was defined algorithmically as occurrence of thromboembolism (TE) and thrombocytopenia (TCP) within 7 days. Incident cases were those with no TE or TCP in the prior year.
Unadjusted incident event rates of TTS per 100,000 person-years (100KPY) were calculated with associated Poisson exact 95% confidence intervals (95%CI). Multivariable logistic regression was used to assess risk factors.

Results: Pre-COVID-19 cohort (N=9,062,313): 201 incident TTS cases were seen, with an incidence rate of 0.42 (95%CI=0.36–0.48) per 100KPY.
COVID-19 cohort (N=39,448): Few incident TTS cases were seen between 28–84 days post COVID-19 disease, precluding incidence rate calculations.
COVID-19 vaccination cohort (N=5,544,761), 20 incident TTS cases were observed within 28 days post vaccination. The TTS incidence rate was 2.41 (95%CI=1.47–3.72) per 100KPY.
In the pre-COVID-19 cohort several risk factors were directly associated with incident TTS: age, deprivation, having a chronic disease, being immunosuppressed, and exposure to anticoagulants or oral contraception. In other cohorts, insufficient cases prevented investigating risk factors.

Conclusions: TTS was rare in all cohorts. Differential covariate distributions preclude crude comparisons of TTS rates across cohorts. In the pre-COVID-19 cohort, the crude TTS incidence rate was comparable to previous studies, whilst the crude incidence rate of TTS after vaccination with AZD1222 (ChAdOx1 nCoV-19) was found to be lower than reported elsewhere. Risk factors for TTS in the pre-COVID cohort overlapped with those for TE and TCP.