Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S

Abstract

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare disorder described after vaccination with adenoviral vector-based COVID-19 vaccines. Co-occurring thrombosis with thrombocytopenia reported after vaccination can be a proxy for identification of TTS.

Methods: Descriptive database review of all cases of co-occurring (within 42 days) thrombosis with thrombocytopenia in participants in Ad26.COV2.S clinical trials or recipients of Ad26.COV2.S in real-world clinical practice. Cases were retrieved from Janssens' clinical trial and Global Medical Safety databases.

Results: There were 34 cases of co-occurring thrombosis with thrombocytopenia in Ad26.COV2.S recipients (46 per 100,000 person-years) and 15 after placebo (75 per 100,000 person-years) in clinical trials. Among Ad26.COV2.S recipients, mean age at the time of the event was 63 years (range 25-85), 82 % were male, mean time-to-onset 112 days (range 8-339) post-last Ad26.COV2.S dose, 26 events occurred post-dose-1, and 7 within a 28-day risk window post-vaccination. Diagnostic certainty was evaluated using Brighton Collaboration, US Centers for Disease Control and Prevention, and European Medicines Agency Pharmacovigilance Risk Assessment Committee case definitions. One case met the highest level of diagnostic certainty for all 3 definitions. There were 355 spontaneous reports of co-occurring thrombosis with thrombocytopenia in the Global Medical Safety database, 47 % males, 85 % within 28-days after vaccination. Twenty-seven cases met the highest level of diagnostic certainty for all definitions, 21 female, 19 with cerebral venous sinus thrombosis, age-range 18-68 years. Time-to-onset was 7-14 days post-vaccination in 20 cases. There were 8 fatalities.

Conclusion: TTS induced by Ad26.COV2.S is very rare. Most co-occurring thrombosis with thrombocytopenia does not constitute TTS.

Keywords: COVID-19; Clinical trial; SARS.CoV.2; Surveillance; Thrombosis with thrombocytopenia syndrome; Vaccine; Vaccine-induced thrombocytopenia with thrombosis.