Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination
- PMID: 33861525
- PMCID: PMC8112532
- DOI: 10.1056/NEJMoa2105385
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination
Abstract
Background: The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity.
Methods: We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.
Results: In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.
Conclusions: Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.
Copyright © 2021 Massachusetts Medical Society.
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Comment in
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Covid-19 vaccine- induced thrombosis and thrombocytopenia-a commentary on an important and practical clinical dilemma.Prog Cardiovasc Dis. 2021 Jul-Aug;67:105-107. doi: 10.1016/j.pcad.2021.05.001. Epub 2021 May 18. Prog Cardiovasc Dis. 2021. PMID: 34019911 Free PMC article. Review. No abstract available.
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VITT after ChAdOx1 nCoV-19 Vaccination.N Engl J Med. 2021 Dec 2;385(23):2202-2203. doi: 10.1056/NEJMc2111026. Epub 2021 Nov 3. N Engl J Med. 2021. PMID: 34731555 No abstract available.
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VITT after ChAdOx1 nCoV-19 Vaccination.N Engl J Med. 2021 Dec 2;385(23):2203-2204. doi: 10.1056/NEJMc2111026. Epub 2021 Nov 3. N Engl J Med. 2021. PMID: 34731556 No abstract available.
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References
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- Johns Hopkins Coronavirus Disease Resource Center. April 2021. (https://coronavirus.jhu.edu).
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