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Andreas Greinacher, Thomas Thiele, Theodore Earl Warkentin, Karin Weißer, Paul Alexander Kyrle, Sabine Eichinger
BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).
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Greinacher, A., Thiele, T., Warkentin, T. E., Weißer, K., Kyrle, P. A., & Eichinger, S. (2021). Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. New England Journal of Medicine, 384(22), 2092–2101. https://doi.org/10.1056/nejmoa2104840
Greinacher, Andreas, et al. "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination." New England Journal of Medicine, vol. 384, no. 22, 2021, pp. 2092–2101, https://doi.org/10.1056/nejmoa2104840.
Greinacher, Andreas, Thomas Thiele, Theodore Earl Warkentin, Karin Weißer, Paul Alexander Kyrle, and Sabine Eichinger. "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination." New England Journal of Medicine 384, no. 22 (2021): 2092–2101. https://doi.org/10.1056/nejmoa2104840.
Greinacher A., Thiele T., Warkentin T. E. [и др.] Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination // New England Journal of Medicine. — 2021. — Vol. 384, № 22. — P. 2092–2101. — URL: https://doi.org/10.1056/nejmoa2104840
@article{greinacher2021thrombotic,
title = {{Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination}},
author = {Andreas Greinacher and Thomas Thiele and Theodore Earl Warkentin and Karin Weißer and Paul Alexander Kyrle and Sabine Eichinger},
journal = {New England Journal of Medicine},
year = {2021},
volume = {384},
number = {22},
pages = {2092--2101},
doi = {10.1056/nejmoa2104840},
url = {https://doi.org/10.1056/nejmoa2104840}
}TY - JOUR AU - Greinacher, Andreas AU - Thiele, Thomas AU - Warkentin, Theodore Earl AU - Weißer, Karin AU - Kyrle, Paul Alexander AU - Eichinger, Sabine TI - Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination JO - New England Journal of Medicine VL - 384 IS - 22 SP - 2092 EP - 2101 PY - 2021 DA - 2021/04/09 DO - 10.1056/nejmoa2104840 UR - https://doi.org/10.1056/nejmoa2104840 ER -
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