Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance: Incidence between 2017 and 2019 and patient profiles from 38.6 million people in six European countries

BackgroundThrombosis with thrombocytopenia syndrome (TTS) has been reported among individuals vaccinated with adenovirus-vectored COVID-19 vaccines. In this study, we describe the background incidence of non-vaccine induced TTS in six European countries. MethodsElectronic medical records from France, the Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction or ischemic stroke, all with concurrent thrombocytopenia, were estimated among the general population of persons in a database between 2017 and 2019. A range of additional potential adverse events of special interest for COVID-19 vaccinations were also studied in a similar manner. FindingsA total of 38611617 individuals were included. Background rates ranged from 1.0 (95% CI: 0.7-1.4) to 8.5 (7.4-9.9) per 100000 person-years for DVT with thrombocytopenia, from 0.5 (0.3-0.6) to 20.8 (18.9-22.8) for PE with thrombocytopenia, from 0.1 (0.0-0.1) to 2.5 (2.2-2.7) for SVT with thrombocytopenia, and from 1.0 (0.8-1.2) to 43.4 (40.7-46.3) for myocardial infarction or ischemic stroke with thrombocytopenia. CVST with thrombocytopenia was only identified in one database, with incidence rate of 0.1 (0.1-0.2) per 100000 person-years. The incidence of non-vaccine induced TTS increased with age, and was typically greater among those with more comorbidities and greater medication use than the general population. It was also more often seen in men than women. A large proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their event. InterpretationAlthough rates vary across databases, non-vaccine induced TTS has consistently been seen to be a very rare event among the general population. While still remaining very rare, rates were typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population.