Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Michael G DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada.
J Thromb Haemost. 2023 Oct;21(10):2833-2843. doi: 10.1016/j.jtha.2023.06.026. Epub 2023 Jun 30.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector-based vaccines against SARS-CoV-2. This syndrome is caused by antibodies against platelet factor 4 (PF4; CXCL4) that lead to platelet activation and is characterized by thrombocytopenia and thrombosis in unusual locations, including cerebral venous sinus thrombosis (CVST). VITT can be classified based on anti-PF4 antibodies properties in vitro: those that require PF4 to activate platelets (PF4-dependent) and those that can activate platelets without additional PF4 (PF4-independent) in the serotonin release assay.
We aim to characterize the relationship of VITT platelet-activating profiles with CVST.
We conducted a retrospective cohort study involving patients with confirmed VITT who were tested between March and June 2021. Data were collected with an anonymized form and cases were identified as VITT with high clinical suspicion according to platelet activation assays. Anti-PF4 antibody binding regions on PF4 were further characterized with alanine scanning mutagenesis.
Of the patients with confirmed VITT (n = 39), 17 (43.6%) had PF4-dependent antibodies and 22 (56.4%) had PF4-independent antibodies. CVST occurred almost exclusively in PF4-independent patients (11 of 22 vs 1 of 17; P < .05). Additionally, PF4-independent antibodies bound to 2 distinct epitopes on PF4, the heparin-binding region and a site typical for heparin-induced thrombocytopenia antibodies, whereas PF4-dependent antibodies bound to only the heparin-binding region.
These findings suggest that VITT antibodies that cause PF4-independent platelet activation represent a unique subset of patients more likely to be associated with CVST, possibly due to the 2 different types of anti-PF4 antibodies.
疫苗诱导的免疫性血栓性血小板减少症（VITT）是一种罕见的 SARS-CoV-2 腺病毒载体疫苗的并发症。该综合征是由针对血小板因子 4（PF4；CXCL4）的抗体引起的，导致血小板激活，并以血小板减少和不常见部位的血栓形成为特征，包括脑静脉窦血栓形成（CVST）。VITT 可根据体外抗 PF4 抗体的特性进行分类：那些需要 PF4 激活血小板的（PF4 依赖性）和那些在 5-羟色胺释放试验中无需额外 PF4 即可激活血小板的（PF4 非依赖性）。
我们旨在描述 VITT 血小板激活谱与 CVST 的关系。
我们进行了一项回顾性队列研究，纳入了 2021 年 3 月至 6 月间检测出的确诊 VITT 患者。数据通过匿名表格收集，根据血小板激活试验确定疑似 VITT 病例。进一步用丙氨酸扫描突变法对 PF4 上的抗 PF4 抗体结合区进行了特征描述。
在确诊的 VITT 患者中（n=39），17 例（43.6%）存在 PF4 依赖性抗体，22 例（56.4%）存在 PF4 非依赖性抗体。CVST 几乎仅发生于 PF4 非依赖性患者（22 例中的 11 例 vs 17 例中的 1 例；P<0.05）。此外，PF4 非依赖性抗体结合到 PF4 上的 2 个不同表位，肝素结合区和肝素诱导的血小板减少症抗体的典型位点，而 PF4 依赖性抗体仅结合肝素结合区。
这些发现表明，导致 PF4 非依赖性血小板激活的 VITT 抗体代表了一组独特的患者亚群，更有可能与 CVST 相关，可能是由于存在 2 种不同类型的抗 PF4 抗体。
