Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Ann Neurol. 2022 Oct;92(4):562-573. doi: 10.1002/ana.26431. Epub 2022 Jul 4.
Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.
We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.
Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54).
In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
疫苗诱导的免疫性血栓性血小板减少症（VITT）引起的脑静脉血栓形成（CVT）是腺病毒载体严重急性呼吸综合征冠状病毒 2 （SARS-CoV-2）疫苗的罕见不良反应。2021 年 3 月，在发现 VITT 的自身免疫发病机制后，制定了治疗建议。这些建议包括免疫调节、非肝素抗凝剂和避免血小板输注。本研究旨在评估这些建议的依从性及其与死亡率的关系。
我们使用了腺病毒载体 SARS-CoV-2 疫苗接种后 CVT 国际前瞻性登记处的数据。我们分析了截至 2022 年 1 月 18 日纳入的可能、可能或明确的 VITT-CVT 病例。免疫调节包括静脉注射免疫球蛋白和/或血浆置换。
分析了来自 17 个国家 71 家医院的 99 例 VITT-CVT 患者。3 月、4 月和 5 月以后诊断的 38 例中的 5 例（13%）、24 例中的 11 例（46%）和 37 例中的 28 例（76%）分别按照 VITT 建议进行治疗（p<0.001）。总体而言，根据建议进行治疗对死亡率没有统计学显著影响（44 例中的 14 例[32%]与 55 例中的 29 例[52%]，调整后的比值比[OR]为 0.43，95%置信区间[CI]为 0.16-1.19）。然而，接受免疫调节治疗的患者死亡率较低（65 例中的 19 例[29%]与 34 例中的 24 例[70%]，调整后的 OR 为 0.19，95% CI 为 0.06-0.58）。使用非肝素抗凝剂而不是肝素抗凝剂治疗与较低的死亡率无关（51 例中的 17 例[33%]与 35 例中的 13 例[37%]，调整后的 OR 为 0.70，95% CI 为 0.24-2.04）。血小板输注也未显著影响死亡率（27 例中的 17 例[63%]与 72 例中的 26 例[36%]，调整后的 OR 为 2.19，95% CI 为 0.74-6.54）。
在 VITT-CVT 患者中，VITT 治疗建议的依从性随着时间的推移而提高。免疫调节似乎对降低 VITT-CVT 的死亡率至关重要。
