Marie Scully , M.D., Deepak Singh , B.Sc., Robert Lown , M.D., Anthony Poles , M.D., Tom Solomon , M.D., Marcel Levi , M.D., David Goldblatt , M.D., Ph.D., Pavel Kotoucek , M.D., William Thomas , M.D., William Lester , M.D.
16 April 2021
Keyword part (code): 2Keyword part (keyword): Hematology/OncologyKeyword part (code): 2_3Keyword part (keyword): Coagulation , 2, Hematology/Oncology, Keyword part (code): 2_3Keyword part (keyword): Coagulation, 2_3, Coagulation, Keyword part (code): 12Keyword part (keyword): Pulmonary/Critical CareKeyword part (code): 12_5Keyword part (keyword): Anticoagulation/Thromboembolism , 12, Pulmonary/Critical Care, Keyword part (code): 12_5Keyword part (keyword): Anticoagulation/Thromboembolism, 12_5, Anticoagulation/Thromboembolism, Keyword part (code): 14Keyword part (keyword): CardiologyKeyword part (code): 14_5Keyword part (keyword): Anticoagulation/Thromboembolism , 14, Cardiology, Keyword part (code): 14_5Keyword part (keyword): Anticoagulation/Thromboembolism, 14_5, Anticoagulation/Thromboembolism, Keyword part (code): 18Keyword part (keyword): Infectious DiseaseKeyword part (code): 18_2Keyword part (keyword): Vaccines , 18, Infectious Disease, Keyword part (code): 18_2Keyword part (keyword): Vaccines, 18_2, Vaccines
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.
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.
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.
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.