Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.
Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany.
Semin Hematol. 2022 Apr;59(2):108-114. doi: 10.1053/j.seminhematol.2022.03.001. Epub 2022 Mar 7.
In hundreds of patients worldwide, vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2.S) triggered platelet-activating anti-platelet factor 4 (PF4) antibodies inducing vaccine-induced immune thrombotic thrombocytopenia (VITT). In most VITT patients, platelet-activating anti-PF4-antibodies are transient and the disorder is discrete and non-recurring. However, in some patients platelet-activating antibodies persist, associated with recurrent thrombocytopenia and sometimes with relapse of thrombosis despite therapeutic-dose anticoagulation. Anti-PF4 IgG antibodies measured by enzyme-immunoassay (EIA) are usually detectable for longer than platelet-activating antibodies in functional assays, but duration of detectability is highly assay-dependent. As more than 1 vaccination dose against COVID-19 is required to achieve sufficient protection, at least 69 VITT patients have undergone subsequent vaccination with an mRNA vaccine, with no relevant subsequent increase in anti-PF4 antibody titers, thrombocytopenia, or thrombotic complications. Also, re-exposure to adenoviral vector-based vaccines in 5 VITT patients was not associated with adverse reactions. Although data are limited, vaccination against influenza also appears to be safe. SARS-CoV-2 infection reported in 1 patient with preceding VITT did not influence anti-PF4 antibody levels. We discuss how these temporal characteristics of VITT provide insights into pathogenesis.
在全球数百名患者中，接种腺病毒载体疫苗（ChAdOx1 nCoV-19；Ad26.COV2.S）可引发血小板激活抗血小板因子 4（PF4）抗体，导致疫苗诱导的免疫性血栓性血小板减少症（VITT）。在大多数 VITT 患者中，血小板激活的抗 PF4 抗体是短暂的，且该疾病是离散且非复发性的。然而，在一些患者中，血小板激活抗体持续存在，与复发性血小板减少症相关，有时即使进行治疗剂量的抗凝治疗，也会出现血栓复发。通过酶联免疫吸附测定（EIA）测量的抗 PF4 IgG 抗体通常比功能测定中血小板激活抗体检测时间更长，但检测时间的长短高度依赖于测定方法。由于需要接种至少 2 剂 COVID-19 疫苗才能达到足够的保护效果，因此至少有 69 例 VITT 患者接受了 mRNA 疫苗的后续接种，其抗 PF4 抗体滴度、血小板减少症或血栓性并发症均无明显增加。此外，5 例 VITT 患者再次接触腺病毒载体疫苗也未发生不良反应。尽管数据有限，但接种流感疫苗似乎也是安全的。1 例 VITT 患者先前感染 SARS-CoV-2，其抗 PF4 抗体水平未受影响。我们讨论了 VITT 的这些时间特征如何为发病机制提供新的见解。
