Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT

IF 3.4 3区 医学 Q2 HEMATOLOGY
Hannah Stevens , James D. McFadyen , Natalie A. Mellett , David J. Lynn , Thy Duong , Corey Giles , Jane James , Rochelle Botten , Georgina Eden , Miriam Lynn , Paul Monagle , Peter J. Meikle , Sanjeev Chunilal , Karlheinz Peter , Huyen Tran
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Abstract

Background

VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination.

Objectives

Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored. Here, we examined the plasma lipidome of patients with VITT and compared it with those following ChAdOx1-S vaccination and with unprovoked venous thromboembolism (VTE) to understand the role of lipids in VITT pathophysiology.

Methods

This was a multicenter, prospective cohort study evaluating plasma lipidomics in newly diagnosed VITT samples, which were compared with both healthy controls following ChAdOx1-S vaccination and with unprovoked VTE.

Results

Comparison with ChAdOx1-S controls reveals a distinct lipid signature in VITT, characterized by elevations in phosphatidylserine and ceramide species, alongside reductions in several plasmalogens and acylcarnitine species. Notably, similarities between VITT lipid profiles and insulin resistance phenotypes suggest potential metabolic susceptibility. While few significant associations were found between VITT and VTE, an inverse correlation with several acylcarnitine species was demonstrated. Given the known anticoagulant role of acylcarnitine species, these findings suggest a plausible mechanistic pathway elevating the thrombotic potential of VITT above that of standard VTE.

Conclusion

These findings underscore the important role of lipid metabolism in VITT pathophysiology and highlight the complex interplay between lipids, coagulation, and pathologic thrombosis.
超越血小板活化:在定义VITT的风险和病理生理中的脂质代谢失调
vitt已成为一种罕见但严重的不良事件,主要与腺病毒载体COVID-19疫苗接种有关,如ChAdOx1-S(牛津/阿斯利康)疫苗接种。该综合征的特征是在接种疫苗42天内形成血栓伴血小板减少、d -二聚体升高和病理性血小板因子4抗体。尽管脂质代谢失调是许多血栓形成条件的基础,但脂质改变在VITT中的作用仍未被探索。在这里,我们检测了VITT患者的血浆脂质组,并将其与接种ChAdOx1-S疫苗和无因性静脉血栓栓塞(VTE)患者的血浆脂质组进行比较,以了解脂质在VITT病理生理中的作用。方法:这是一项多中心、前瞻性队列研究,评估新诊断的VITT样本的血浆脂质组学,将接种ChAdOx1-S疫苗的健康对照组和非诱发性静脉血栓栓塞对照组进行比较。结果与ChAdOx1-S对照相比,VITT中有明显的脂质特征,其特征是磷脂酰丝氨酸和神经酰胺种类升高,同时几种磷脂原和酰基肉碱种类减少。值得注意的是,VITT脂质谱和胰岛素抵抗表型之间的相似性表明潜在的代谢易感性。虽然VITT和VTE之间没有明显的关联,但与几种酰基肉碱物种呈负相关。鉴于已知的酰基肉碱的抗凝作用,这些发现提示了一种可能的机制途径,使VITT的血栓形成电位高于标准静脉血栓栓塞电位。结论这些发现强调了脂质代谢在VITT病理生理中的重要作用,并强调了脂质、凝血和病理性血栓形成之间的复杂相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.60
自引率
13.00%
发文量
212
审稿时长
7 weeks
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