Brolucizumab and Platelet Activation and Reactivity.

IF 1.7 4区 医学 Q3 OPHTHALMOLOGY
Current Eye Research Pub Date : 2025-04-01 Epub Date: 2025-01-06 DOI:10.1080/02713683.2024.2441245
B Sobolewska, S Poeschel, H Kalbacher, K Bieber, A M Paczulla Stanger, Konstantinos Stellos, F Ziemssen
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引用次数: 0

Abstract

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.6 µg/mL, 3 µg/mL, 6 µg/mL, 300 µg/mL, and 3000 µ/mL or its solvent or PBS. The surface expression of platelet activation markers GPIIb/IIIa and P-selectin was determined by multispectral imaging flow cytometry, which combines flow cytometry and fluorescence microscopy. Two different methods were used to examine the interaction of brolucizumab with platelets: 1) A cross-pretreatment experiment was performed with FITC-labeled brolucizumab and bevacizumab; 2) Resting and activated platelets were pretreated with brolucizumab or its solvent or PBS, followed by anti-brolucizumab antibody generated by rabbit immunization.

Results: Brolucizumab did not significantly affect platelet activation compared to solvent or PBS, across a range of concentrations. No significant upregulation of CD62P and no activation of the fibrinogen receptor (GPIIb/IIa) were observed in resting and TRAP-activated platelets. After pretreatment with PBS, the level of brolucizumab-FITC was significantly lower in comparison to bevacizumab-FITC (normalized MFI = 3.32, CI = 3.16-3.48 vs. normalized MFI = 7.19, CI = 7.04-7.35; p < 0.001). Both brolucizumab- and bevacizumab-FITC were downregulated after pretreatment with brolucizumab or bevacizumab compared to pretreatment with PBS. Antibodies against brolucizumab did not show any significant difference between pretreatment with brolucizumab and its solvent in resting and TRAP-activated platelets.

Conclusion: Brolucizumab does not appear to directly affect platelet activation or reactivity to thrombin receptor agonists. No platelet interaction was observed after increasing brolucizumab concentrations or anti-brolucizumab antibodies in resting and activated platelets. However, brolucizumab might be taken up in platelets.

Brolucizumab与血小板活化和反应性。
目的:本研究探讨brolucizumab与血小板的潜在相互作用及其对血小板活化和反应性的影响,血小板活化和反应性在视网膜血管炎和视网膜血管闭塞中至关重要。安全性问题仍然值得关注,尽管与其他许可的抗vegf药物相比,brolucizumab显示出更好的视网膜疗效和更少的注射频率。方法:健康志愿者静息血小板和活化血小板分别以以下浓度(0.6µg/mL、3µg/mL、6µg/mL、300µg/mL、3000µg/mL或其溶剂或PBS)预处理。采用流式细胞术和荧光显微镜相结合的多光谱成像流式细胞术检测血小板活化标志物GPIIb/IIIa和p -选择素的表面表达。采用两种不同的方法检测brolucizumab与血小板的相互作用:1)采用fitc标记的brolucizumab与贝伐单抗进行交叉预处理实验;2)静息血小板和活化血小板用brolucizumab或其溶剂或PBS预处理,然后兔免疫产生抗brolucizumab抗体。结果:在不同浓度范围内,与溶剂或PBS相比,Brolucizumab对血小板活化没有显著影响。在静息和trap活化的血小板中,未观察到CD62P的显著上调和纤维蛋白原受体(GPIIb/IIa)的激活。PBS预处理后,brolucizumab-FITC水平明显低于bevacizumab-FITC(归一化MFI = 3.32, CI = 3.16-3.48 vs归一化MFI = 7.19, CI = 7.04-7.35;P < 0.001)。与PBS预处理相比,布卢珠单抗或贝伐单抗预处理后,布卢珠单抗和贝伐单抗- fitc均下调。在静息血小板和trap活化血小板中,抗brolucizumab的抗体在brolucizumab预处理和其溶剂之间没有显示出任何显著差异。结论:Brolucizumab似乎不会直接影响血小板活化或对凝血酶受体激动剂的反应性。在静息血小板和活化血小板中增加brolucizumab浓度或抗brolucizumab抗体后,未观察到血小板相互作用。然而,brolucizumab可能被血小板吸收。
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
Current Eye Research
Current Eye Research 医学-眼科学
CiteScore
4.60
自引率
0.00%
发文量
163
审稿时长
12 months
期刊介绍: The principal aim of Current Eye Research is to provide rapid publication of full papers, short communications and mini-reviews, all high quality. Current Eye Research publishes articles encompassing all the areas of eye research. Subject areas include the following: clinical research, anatomy, physiology, biophysics, biochemistry, pharmacology, developmental biology, microbiology and immunology.
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