• Marie Scully, Deepak Singh, Robert Lown, Anthony Poles, Tom Solomon, Marcel Levi, David Goldblatt, Pavel Kotoucek, William Thomas, and William Lester.
• From the Department of Haematology, University College London Hospitals NHS Foundation Trust (M.S., M.L.), National Institute for Health Research University College London Hospitals Biomedical Research Centre (M.S., M.L.), Special Coagulation, Health Services Laboratories (D.S.), Great Ormond Street Institute of Child Health, University College London (D.G.), and National Institute for Health Research Great Ormond Street Biomedical Research Centre (D.G.), London, the Department of Haematology, University Hospital Southampton, Southampton (R.L.), National Health Service Blood and Transplant, Bristol (A.P.), National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool (T.S.), the Department of Haematology, Mid Essex Hospitals, Chelmsford (P.K.), the Department of Haematology, Addenbrookes Hospital, Cambridge (W.T.), and the Department of Haematology, University Hospitals Birmingham, and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (W.L.) - all in the United Kingdom; and the Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam (M.L.).
• N. Engl. J. Med. 2021 Jun 10; 384 (23): 2202-2211.

BackgroundThe 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.MethodsWe 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.ResultsIn 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.ConclusionsVaccination 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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