The study investigates the development of thrombotic thrombocytopenia (TTP) following vaccination with the ChAdOx1 nCov-19 vaccine, a recombinant adenoviral vector encoding the spike protein of SARS-CoV-2. The authors report on 11 patients in Germany and Austria who developed thrombotic events, including cerebral venous thrombosis, splanchnic-vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation, following vaccination. All patients presented with thrombocytopenia, and none had received heparin before symptom onset. The study found that serum from these patients strongly activated platelets in the presence of platelet factor 4 (PF4)–heparin antibodies, which were detected using a PF4-enhanced platelet-activation test. The findings suggest that vaccination with ChAdOx1 nCov-19 can lead to immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, similar to autoimmune heparin-induced thrombocytopenia. The authors recommend using PF4-dependent ELISA or PF4-enhanced platelet-activation assays to diagnose this novel condition and suggest high-dose intravenous immune globulin and nonheparin anticoagulants as potential treatments.The study investigates the development of thrombotic thrombocytopenia (TTP) following vaccination with the ChAdOx1 nCov-19 vaccine, a recombinant adenoviral vector encoding the spike protein of SARS-CoV-2. The authors report on 11 patients in Germany and Austria who developed thrombotic events, including cerebral venous thrombosis, splanchnic-vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation, following vaccination. All patients presented with thrombocytopenia, and none had received heparin before symptom onset. The study found that serum from these patients strongly activated platelets in the presence of platelet factor 4 (PF4)–heparin antibodies, which were detected using a PF4-enhanced platelet-activation test. The findings suggest that vaccination with ChAdOx1 nCov-19 can lead to immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, similar to autoimmune heparin-induced thrombocytopenia. The authors recommend using PF4-dependent ELISA or PF4-enhanced platelet-activation assays to diagnose this novel condition and suggest high-dose intravenous immune globulin and nonheparin anticoagulants as potential treatments.