Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study,The Lancet

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Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study
The Lancet ( IF 98.4 ) Pub Date : 2021-08-06 , DOI: 10.1016/s0140-6736(21)01608-1
Richard J Perry ₁ , Arina Tamborska ₂ , Bhagteshwar Singh ₃ , Brian Craven ₄ , Richard Marigold ₅ , Peter Arthur-Farraj ₆ , Jing Ming Yeo ₇ , Liqun Zhang ₈ , Ghaniah Hassan-Smith ₉ , Matthew Jones ₁₀ , Christopher Hutchcroft ₁₀ , Esther Hobson ₁₁ , Dana Warcel ₄ , Daniel White ₉ , Phillip Ferdinand ₁₂ , Alastair Webb ₁₃ , Tom Solomon ₁₄ , Marie Scully ₁₅ , David J Werring ₁ , Christine Roffe ₁₆ ,

Affiliation

Comprehensive Stroke Service, National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust, London, UK; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool University Hospital, Liverpool, UK.
Department of Haematology, UCL Hospitals NHS Foundation Trust, London, UK.
Department of Stroke Medicine, University Hospital Southampton NHS Foundation Trust, Southampton UK.
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge, UK.
Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Department of Neurology, St George's University Hospital NHS Foundation Trust, London, UK.
Department of Neurology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.
Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Stroke Service, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Department of Neurology, Walton Centre NHS Foundation Trust, Liverpool, UK.
Department of Haematology, UCL Hospitals NHS Foundation Trust, London, UK; Haemostasis Research Unit, University College London, London, UK.
Stroke Service, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK; Faculty of Medicine and Health Sciences, Keele University, Stoke-on-Trent, UK.

Background

A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes.

Methods

For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 10⁹ per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3–6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis.

Findings

Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32–55) was lower than in the non-VITT group (57 years; 41–62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2–4) than non-VITT patients (two, 2–3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022).

Interpretation

Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate.

Funding

None.

中文翻译：

在英国接种 COVID-19 疫苗后的脑静脉血栓形成：一项多中心队列研究

背景

疫苗诱导的免疫性血栓性血小板减少症 (VITT) 的新综合征已成为 COVID-19 疫苗接种的罕见副作用。脑静脉血栓形成是该综合征最常见的表现，但据我们所知，此前并未对其进行详细描述。我们的目的是记录有和没有 VITT 的疫苗接种后脑静脉血栓形成的特征，并评估 VITT 是否与较差的结果相关。

方法

对于这项多中心队列研究，临床医生被要求提交在脑静脉血栓形成之前接种 COVID-19 疫苗的所有病例，无论疫苗的类型、疫苗接种与脑静脉血栓形成症状发作之间的间隔或验血结果如何。我们收集了接种 COVID-19 疫苗后脑静脉血栓形成患者入院时的临床特征、实验室结果（包括可用的抗血小板因子 4 抗体检测结果）和放射学特征，没有排除标准。如果入院期间记录的最低血小板计数低于 150 × 10 ^{9 ，我们将脑静脉血栓形成病例定义为 VITT 相关病例}每升，如果测量 D-二聚体，记录的最高值大于 2000 微克/升。我们比较了 VITT 组和非 VITT 组在入院结束时死亡或依赖他人帮助他们进行日常生活活动（改良 Rankin 评分 3-6）的患者比例（主要结果是研究）。还将 VITT 组与国际脑静脉和硬脑膜窦血栓形成研究中描述的大量脑静脉血栓形成患者进行了比较。

发现

2021 年 4 月 1 日至 5 月 20 日期间，我们从英国 43 家医院的合作者那里收到了 99 名患者的数据。四名患者被排除在外，因为他们在影像学上没有明确的脑静脉血栓形成证据。在其余 95 名患者中，70 名有 VITT，25 名没有。VITT 组的中位年龄（47 岁，IQR 32-55）低于非 VITT 组（57 岁；41-62；p=0·0045）。VITT 相关脑静脉血栓形成患者比非 VITT 患者（2 个，2-3；p=0·041）颅内静脉血栓形成更多（中位数 3 个，IQR 2-4），并且颅外血栓形成更频繁（31 [44 %] 的 70 名患者）与非 VITT 患者（25 名患者中的一名 [4%]；p=0·0003）进行比较。与非 VITT 对照组（25 名患者中的 4 名 [16%]；p=0 ·0061). 与未接受非肝素抗凝剂的患者（20 名患者中的 15 名 [75%]；p=0·0031）相比，接受非肝素抗凝剂的 VITT 患者（50 名患者中的 18 名 [36%]）发生这种不良结果的频率较低，并且接受静脉注射免疫球蛋白的患者（55 名患者中的 22 名 [40%]）与未接受静脉注射免疫球蛋白的患者（15 名患者中的 11 名 [73%]；p=0·022）。