Thromboembolism after Astra Zeneca COVID-19 vaccine: Not always PF4- antibody mediated

Cases of thromboembolic events in 2021 flared up the discussion about the safety of Astra Zeneca's AZD1222 vaccine. We hereby report three cases of pulmonary embolism (PE), one case of extended portal vein thrombosis, and one case of combined portal vein thrombosis and PE within 2 weeks after vaccination with the Astra Zeneca AZD1222 vaccine in a 60-year-old, a 50-year old, a 33-year-old, a 30-year old, and a 40-year-old male in that year. All patients were healthy before. In three patients, we observed thrombocytopenia and to some extent unusually low antibody levels for the Spike Protein (S-protein), while the other two had normal thrombocyte counts. Only one patient had anti-platelet factor 4 (PF4)-antibodies detectable as it has been described in the "heparin-induced thrombocytopenia (HIT)-like" disease of "vaccine-induced prothrombotic immune thrombocytopenia" (VIPIT) and we therefore assume that heterogeneous mechanisms led to PE. Therefore, we advise to collect and report more cases, in order to determine the age-related risks of vaccination balanced against the benefits of immunity to SARS-COV-2 for the AZD1222 vaccine in order to gain knowledge for the next pandemic.