Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination.
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination.
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DOI：
10.1056/nejmoa2105385
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发表时间：
2021-06-10
期刊：
影响因子：
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通讯作者：
Lester W
中科院分区：
文献类型：
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作者：
Scully M;Singh D;Lown R;Poles A;Solomon T;Levi M;Goldblatt D;Kotoucek P;Thomas W;Lester W
控制2019冠状病毒病（Covid-19）大流行的主要措施是接种严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）疫苗。在一年之内，已经开发出几种疫苗，并提供了数百万剂。不良事件报告是一项关键的上市后活动。我们报告了23名患者的结果，这些患者在接受第一剂ChAdOx 1 nCoV-19疫苗（阿斯利康）后6至24天出现血栓形成和血小板减少症。在其临床和实验室特征的基础上，我们确定了一个新的潜在机制，并解决治疗的影响。在既往无血栓前疾病的情况下，22例患者出现急性血小板减少症和血栓形成，主要是脑静脉血栓形成，1例患者出现孤立性血小板减少症和出血表型。所有患者在就诊时纤维蛋白原水平低或正常，d-二聚体水平升高。未发现血栓形成倾向或致病沉淀物的证据。22例患者的血小板因子4（PF 4）抗体检测结果为阳性（1例结果不明确），1例患者为阴性。根据这些患者的病理生理学特征，我们建议避免血小板输注治疗，因为血栓形成症状有进展的风险，首次出现这些症状时应考虑使用非肝素抗凝剂和静脉注射免疫球蛋白。针对SARS-CoV-2的疫苗接种对于控制Covid-19大流行仍然至关重要。ChAdOx 1 nCoV-19疫苗接种后可能发生与肝素治疗无关的致病性PF 4依赖性综合征。快速识别这种罕见的综合征是重要的，因为治疗的影响。
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.