Characteristics of Spontaneous Reports of Thrombosis with Thrombocytopenia Syndrome after COVID-19 Vaccines in the Netherlands: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: In March 2021 first cases of thrombosis with thrombocytopenia syndrome (TTS), also called vaccine induced thrombosis with thrombocytopenia (VITT), were published and reported, raising a concern with the adenovector vaccine of AstraZeneca [1, 2]. One month later, TTS was also associated with the Janssen vaccine [3]. No conclusive evidence of VITT with mRNA vaccines is found [4]. In Europe, vaccination programmes were put on hold and the indications for use restricted. The role of pharmacovigilance was to monitor the events closely and estimate its frequency of occurrence. While mass vaccination campaigns were ongoing, information on case criteria and definitions was limited. In the Netherlands, internists wrote guidelines, organised centralised diagnostics for PF4 ELISA and HIPA tests and encouraged expert physicians to report suspected cases to The Netherlands Pharmacovigilance Centre Lareb [5]. Lareb managed to monitor TTS cases closely by a fast triage of relevant reports and strong collaboration with external specialists. Objective: Spontaneously reported cases of TTS in The Netherlands are described. Methods: We used CDC classification criteria combined with Dutch guidelines to determine confirmed and strongly suspected cases. CDC classification recognizes 'tier 1' with thrombosis at unusual sites not requiring tests and 'tier 2' with common types of thrombosis and requiring confirmatory tests [6]. Results: In total, 75 cases of thrombocytopenia with any kind of thrombosis were reported. Only 26 reports met criteria of TTS, concerning 19 AstraZeneca, 5 Janssen and 2 mRNA vaccines. The majority (23;89%) of the cases was reported following the first dose. Reporting rates for AstraZeneca and Janssen were 7.7 and 5.7 per million vaccinations in total, respectively, and 13.4 per million vaccinations of the first dose with AstraZeneca. Patient and report characteristics are described in table 1. 'Tier 1' criteria were met in 15 cases. 'Tier 2' criteria were met in 6 cases and in 5 cases TTS was strongly suspected based on the Dutch guidelines. A functional HIPA test was performed in 20 cases of which 17 were positive and 3 negative. Also, two reports were received with mRNA vaccines, one well documented with positive PF4-ELISA and HIPA-tests (Moderna, 3rd dose) and the other poorly documented but meeting 'tier 1' criteria (Pfizer, 1st dose). Conclusion: In The Netherlands, TTS was predominantly reported after the first dose of the AstraZeneca vaccine, similar to other countries [1]. Intensive collaboration between clinical practice and pharmacovigilance resulted in good monitoring of TTS cases with spontaneous reporting.