Estimating the Incidence of Co-occurring Thrombosis and Thrombocytopenia in a Healthcare Database

Background: The safety of COVID-19 vaccines remains an important global public health priority. Thrombosis with thrombocytopenia syndrome (TTS) is an important but very rare prothrombotic disorder that is a safety concern for some COVID-19 vaccines. Definitions of TTS have been published by the Brighton Collaboration and US CDC but have only been used for confirming individual cases. A few real-world data studies have evaluated patterns of co-occurrence of thrombosis and thrombocytopenia as a potentially sensitive and non-specific proxy for TTS in claims and electronic health record databases.

Objectives: To assess the incidence of co-occurrence of thrombosis with thrombocytopenia (TWT) diagnosis codes prior to the pandemic using the National Health Insurance Research Database in Taiwan, which covers >99% of the population of Taiwan and is linked to the Taiwan death registry.

Methods: We conducted a population-based retrospective cohort study to estimate TWT rates over the 3-year-period prior to the SARS-COV-2 pandemic (2017-2019). TWT was defined as patients with newly diagnosed thrombosis (ICD-10 G43.6, I26, I60, I61, I62, I63, I67.6, I70.92, I74, I75, I80.2, I82, P91), and with co-occurrence of newly diagnosed thrombocytopenia (D69.3, D69.4, D69.5, D69.6) within a ± 7-day period. All newly diagnosed cases were linked to the Death Registry to estimate mortality

Results: We identified 2010 patients with newly diagnosed TWT between 1 Jan 2017 and 31 Dec 2019. The median age was 66 years and female to male ratio was 1: 1.45. The most frequent thrombotic events were hemorrhagic stroke (21%), coronary artery disease-related (19%), cerebral infarction (17%), and disseminated intravascular coagulation (13%). Fewer than 0.1% were cerebral venous sinus thromboses.
The mean annual incidence rate of TWT per 100,000 population was 2.84, and increased with age; from 0.3 in 0 — 19 year old, 0.62 in adults aged 20 — 39 years, and increased steadily to 19.42 in adults ≥ 80 years of age. The overall observed incidence rate was higher in men (3.38 per 100 000 population) than women (2.3 per 100 000 population) except in the age-group of 20-39 years old, where a higher risk was observed in young females. 20.6% of patients died within the first month after the occurrence of thrombosis with thrombocytopenia.

Conclusions: The TWT rate was low during the pre- COVID pandemic period. However, demographic and disease characteristics of TWT is different from TTS, Further research is needed to use suitable data sources with clinical laboratory results to identify the TTS.