ChAdOx1疫苗接种后抗血小板因子4的病理抗体分析
2021-04-28   阅读:645   来源:新英格兰医学杂志

英国伦敦大学学院医院NHS基金会信托基金Marie Scully团队研究了新冠病毒ChAdOx1疫苗接种后抗血小板因子4的病理抗体。2021年4月16日,该研究发表在《新英格兰医学杂志》上。

控制Covid-19大流行的主要措施是接种SARS-CoV-2疫苗。在一年之内,科研人员已经研制出了几种疫苗,并提供了数百万剂供人们接种。不良事件报告是一项重要的上市后活动。

研究组报告了23例在接种第一剂ChAdOx1-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的患者的研究结果。根据这些患者的临床和实验室特点,研究组确定了一种新的潜在机制,并提出治疗方案。

在既往无血栓前疾病的情况下,22例患者表现为急性血小板减少和血栓形成,主要是脑静脉血栓形成,1例表现为孤立性血小板减少和出血表型。所有患者均出现低或正常的纤维蛋白原水平和D-二聚体水平升高。未发现血栓形成或致病沉淀的证据。

血小板因子4(PF4)抗体检测阳性22例(1例可疑),阴性1例。根据这些患者的病理生理学特征,研究组建议避免血小板输注治疗,因为血小板输注有进展血栓症状的风险,并且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。

总之,接种SARS-CoV-2疫苗对于控制Covid-19大流行仍然至关重要。接种ChAdOx1-nCoV-19疫苗后,可出现与肝素治疗无关的致病性PF4依赖综合征。出于治疗对策,快速识别这种罕见的综合征尤为重要。

附:英文原文

Title: Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination

Author: Marie Scully, M.D.,, Deepak Singh, B.Sc.,, Robert Lown, M.D.,, Anthony Poles, M.D.,, Thomas Solomon, M.D.,, Marcel Levi, M.D.,, David Goldblatt, M.D., Ph.D.,, Pavel Kotoucek, M.D.,, William Thomas, M.D.,, and William Lester, M.D.

Issue&Volume: 2021-04-16

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.

DOI: 10.1056/NEJMoa2105385

 

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