ABSTRACT
Background: SARS-CoV-2 adenoviral-vector-DNA vaccines have been linked to the rare but serious thrombotic post-vaccine complication vaccine-induced immune thrombotic thrombocytopenia (VITT). This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 healthcare personnel, 521 were recruited post-vaccination after a first dose of adenoviral vector ChAdOx1-S (Vaxzevria®, AstraZeneca) vaccine, and 46 prospectively before vaccination with an mRNA vaccine, either Spikevax® (Moderna, n=38) or Comirnaty® (Pfizer-BioNTech, n=8). In the mRNA group, samples were acquired before and 1-2 weeks after vaccination. In addition to pre-vaccination samples, 56 unvaccinated blood donors were recruited as controls (total n=102). Thrombin generation, D-dimer and free tissue factor pathway inhibitor (TFPI) were analyzed. Results: No participant experienced thrombosis, VITT or thrombocytopenia (platelet count <100·109/L) one week to one month post-vaccination. There was no increase in thrombin generation, D-dimer or TFPI in the ChAdOx1-S vaccine group compared with controls, or after the mRNA vaccines compared with baseline values. Eleven of 513 vaccinated with ChAdOx1-S (2.1%) had anti-PF4/polyanion antibodies without concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer or TFPI levels compared with baseline or unvaccinated controls. These findings argue against subclinical activation of coagulation post-COVID-19 vaccination.