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富含纤维蛋白/血小板的凝块组织学提示隐源性卒中中心源性栓塞性卒中病因:血栓-CARE(用于明确病因的构型分析)

Thrombo-CARE-cardioembolic stroke etiology in cryptogenic stroke suggested by fibrin-/platelet-rich clot histology : Thrombo-CARE (configuration analysis to refine etiology).

作者信息

Schwarzenhofer Daniel C, von Oertzen Tim, Weis Serge, Sonnberger Michael, Gruber Joachim, Tröscher Anna, Wagner Helga, Hermann Philipp, Grubauer Birgit, Wagner Judith

机构信息

Department of Neurology, Neuromed Campus, Kepler University Hospital, Wagner-Jauregg-Weg 15, 4020, Linz, Austria.

Division of Neuropathology, Neuromed Campus, Department of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.

出版信息

Wien Med Wochenschr. 2025 Jun;175(9-10):227-236. doi: 10.1007/s10354-024-01060-w. Epub 2024 Nov 11.

DOI:10.1007/s10354-024-01060-w
PMID:39527331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12089195/
Abstract

BACKGROUND

Despite extensive diagnostic efforts, the etiology of stroke remains unclear in up to 30% of patients. Mechanical thrombectomy (MT) potentially enhances etiological determination by (immuno)histological analysis of retrieved thrombotic material.

METHODS

In this monocentric exploratory study, clots from 200 patients undergoing MT were investigated by hematoxylin and eosin, CD3, and CD45 staining. Semiquantitative and computer-based image analysis defined the histological composition and relative fractions of immunohistochemically stained areas. First, we correlated these results with strokes of known etiology. Subsequently, clots of unknown source were characterized with regard to their (immuno)histological profile to attempt etiological classification.

RESULTS

Samples from 198 patients were accessible for analysis. Fibrin-/platelet-rich histology appeared in 45 (23%), erythrocyte-rich in 18 (9%), and mixed histology in 123 (62%) patients. Etiology was classified as cardioembolic in 87 (44%), arterioembolic in 37 (19%), and as cryptogenic stroke (CS) in 26 (13%) cases. 20 (23%) patients with cardioembolic stroke and 5 (14%) patients with arterioembolic stroke had fibrin-/platelet-rich clots. 8 (22%) patients with arterioembolic stroke and 1 (1%) patient with cardioembolic stroke had erythrocyte-rich clots. In CS, cardioembolic clot features appeared more than twice as often as arterioembolic clot features. Whereas the association between histology and etiology was significant (p = 0.0057), CD3/CD45 staining did not correlate.

CONCLUSION

A significant association between histology and etiology was observed, with the proportion of erythrocyte-rich thrombi being largest among arterioembolic strokes and the proportion of fibrin-/platelet-rich thrombi highest among cardioembolic strokes. A high number of clots from CS presented histological features of cardioembolic clots. Thus, patients with CS and fibrin-/platelet-rich clots particularly require long-term cardiac rhythm monitoring and may benefit from oral anticoagulation.

摘要

背景

尽管进行了广泛的诊断工作,但仍有高达30%的患者中风病因不明。机械取栓术(MT)有可能通过对取出的血栓物质进行(免疫)组织学分析来加强病因判定。

方法

在这项单中心探索性研究中,对200例行MT的患者的血凝块进行苏木精-伊红染色、CD3和CD45染色。半定量和基于计算机的图像分析确定了免疫组织化学染色区域的组织学组成和相对比例。首先,我们将这些结果与已知病因的中风进行关联。随后,对来源不明的血凝块的(免疫)组织学特征进行描述,以尝试进行病因分类。

结果

198例患者的样本可用于分析。45例(23%)患者的组织学表现为富含纤维蛋白/血小板,18例(9%)为富含红细胞,123例(62%)为混合组织学。病因分类为心源性栓塞的有87例(44%),动脉源性栓塞的有37例(19%),不明原因卒中(CS)的有26例(13%)。20例(23%)心源性栓塞性中风患者和5例(14%)动脉源性栓塞性中风患者的血凝块富含纤维蛋白/血小板。8例(22%)动脉源性栓塞性中风患者和1例(1%)心源性栓塞性中风患者的血凝块富含红细胞。在CS中,心源性栓塞性血凝块特征出现的频率是动脉源性栓塞性血凝块特征的两倍多。虽然组织学与病因之间存在显著关联(p = 0.0057),但CD3/CD45染色无相关性。

结论

观察到组织学与病因之间存在显著关联,富含红细胞的血栓比例在动脉源性栓塞性中风中最高,富含纤维蛋白/血小板的血栓比例在心源性栓塞性中风中最高。大量CS患者的血凝块呈现心源性栓塞性血凝块的组织学特征。因此,CS且血凝块富含纤维蛋白/血小板的患者尤其需要长期心律监测,可能会从口服抗凝治疗中获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f747/12089195/ec3543571f14/10354_2024_1060_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f747/12089195/36607aac3751/10354_2024_1060_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f747/12089195/ec3543571f14/10354_2024_1060_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f747/12089195/36607aac3751/10354_2024_1060_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f747/12089195/ec3543571f14/10354_2024_1060_Fig2_HTML.jpg

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本文引用的文献

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JAMA. 2024 Feb 20;331(7):573-581. doi: 10.1001/jama.2023.27188.
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Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.阿哌沙班与阿司匹林用于不明来源栓塞性脑卒中的比较。
NEJM Evid. 2024 Jan;3(1):EVIDoa2300235. doi: 10.1056/EVIDoa2300235. Epub 2023 Dec 22.
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Thromboinflammatory challenges in stroke pathophysiology.血栓炎症挑战在中风病理生理学。
Semin Immunopathol. 2023 May;45(3):389-410. doi: 10.1007/s00281-023-00994-4. Epub 2023 Jun 5.
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Is Composition of Brain Clot Retrieved by Mechanical Thrombectomy Associated with Stroke Aetiology and Clinical Outcomes in Acute Ischemic Stroke?-A Systematic Review and Meta-Analysis.机械取栓术取出的脑血凝块成分与急性缺血性卒中的病因及临床结局相关吗?一项系统评价和Meta分析
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Prolonged Cardiac Monitoring and Stroke Recurrence: A Meta-analysis.长期心脏监测与卒中复发:一项荟萃分析。
Neurology. 2022 May 10;98(19):e1942-e1952. doi: 10.1212/WNL.0000000000200227. Epub 2022 Mar 9.
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Stroke Etiology and Outcomes after Endovascular Thrombectomy: Results from the SITS Registry and a Meta-Analysis.血管内血栓切除术治疗后的卒中病因与预后:来自SITS注册研究及一项荟萃分析的结果
J Stroke. 2021 Sep;23(3):388-400. doi: 10.5853/jos.2021.00850. Epub 2021 Sep 30.
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First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule.应用组织学 THROMBEX 分类规则,初步区分个体脑卒中患者的心脏性和动脉粥样硬化性栓子。
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