Background: Anti-SARS-CoV-2 adenoviral-vectored-DNA vaccines have been linked to a rare but serious thrombotic post-vaccine complication called the vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT has raised concerns regarding the possibilities of increased thrombotic risk and thrombocytopenia after anti-COVID-19 vaccines.
Aims: To investigate whether anti-SARS-CoV-2 vaccines can cause thrombocytopenia, coagulation activation and increased thrombin generation leading to a hypercoagulable state.
Methods: In this study, 567 healthcare personnel were included from two hospitals in Norway after obtaining informed consent. Of these, 521 were recruited 11-57 days post-vaccination with the first dose of ChAdOx1-S (Vaxzevria®, AstraZeneca, UK) vaccine, and 46 were recruited prospectively prior vaccination with an mRNA vaccine, either elasomeran (Spikevax, Moderna, n=38) or tozinameran (Comirnaty, Pfize-BioNTech, n=8). In the latter group, samples were acquired before and 1-2 weeks after vaccination. In addition to pre-vaccination samples, 56 unvaccinated healthy blood donors were recruited as controls (total n=102). Thrombin generation and D-dimer were analyzed.
Results: None of the participants developed thrombosis/VITT. 12% reported cutaneous bleeding after vaccination, however, none had thrombocytopenia with platelet count <100·109/L. There were no significant differences in D-dimer or the parameters of thrombin generation between the two vaccine groups and the controls (Table 1). Anti-PF4/polyanion antibodies (optical density ≥0.4) were found in 11 of 513 individuals vaccinated with ChAdOx1-S vaccine (2.1%). None of the controls had anti-PF4/polyanion antibodies. Thrombin generation and D-dimer were not found to be higher in the ChAdOx1-S vaccinated individuals with anti-PF4 antibodies than in those without anti-PF4/polyanion antibodies. No differences in thrombin generation between the ChAdOx1-S group and the mRNA group. The median D-dimer level was slightly higher in the ChAdOx1-S group than the mRNA group, but both were within the normal range (Table 1). Thrombin generation and D-dimer showed no changes after mRNA vaccination compared with baseline.
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Summary/Conclusion: Anti-COVID-19 vaccines, both ChAdOx1-S and mRNA vaccines, did not lead to an increase in thrombin generation or D-dimer compared with controls, not even in the ChAdOx1-S vaccinated individuals with anti-PF4/polyanion antibodies. No differences were found between ChAdOx1-S and mRNA vaccines, and no increase in thrombin generation or D-dimer was found after mRNA vaccines compared with baseline levels. Our results are reassuring in the sense that no subclinical activation in the coagulation system was observed with these vaccines.