CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(03): 415-426
DOI: 10.1055/a-1522-4507
Stroke, Systemic or Venous Thromboembolism

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke

Takaya Kitano
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
2   Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan
,
Yumiko Hori
3   Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Shuhei Okazaki
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Yuki Shimada
4   Department of Neurology, Osaka General Medical Center, Osaka, Japan
,
Takanori Iwamoto
2   Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan
,
Hideaki Kanki
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Shintaro Sugiyama
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Tsutomu Sasaki
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hajime Nakamura
5   Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan
,
Naoki Oyama
2   Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan
,
Taku Hoshi
4   Department of Neurology, Osaka General Medical Center, Osaka, Japan
,
Goichi Beck
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hiroki Takai
6   Department of Neurosurgery, Kawasaki Medical School, Okayama, Japan
,
Shunji Matsubara
6   Department of Neurosurgery, Kawasaki Medical School, Okayama, Japan
,
Hiroya Mizuno
7   Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hirotake Nishimura
8   Department of Pathology, Kawasaki Medical School, Okayama, Japan
,
Ryo Tamaki
9   Department of Neurosurgery, Osaka General Medical Center, Osaka, Japan
,
Junichi Iida
9   Department of Neurosurgery, Osaka General Medical Center, Osaka, Japan
,
Jiro Iba
10   Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
,
Masaaki Uno
6   Department of Neurosurgery, Kawasaki Medical School, Okayama, Japan
,
Haruhiko Kishima
5   Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hiroaki Fushimi
11   Department of Pathology, Osaka General Medical Center, Osaka, Japan
,
Satoshi Hattori
12   Department of Integrated Medicine, Biomedical Statistics, Osaka University Graduate School of Medicine, Osaka, Japan
13   Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan
,
Shigeo Murayama
14   Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University, Osaka, Japan
15   Department of Neurology and Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
,
Eiichi Morii
3   Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Manabu Sakaguchi
4   Department of Neurology, Osaka General Medical Center, Osaka, Japan
,
Yoshiki Yagita
2   Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan
,
Takeshi Shimazu
10   Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hideki Mochizuki
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Kenichi Todo
1   Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
› Author Affiliations
Funding This work was supported by JSPS KAKENHI [grants TK19K20729 and JSPS KAKENHI 21K15696].

Abstract

Background Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism.

Methods We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age.

Results Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6–21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24–0.99).

Conclusion An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Supplementary Material



Publication History

Received: 02 March 2021

Accepted: 22 May 2021

Publication Date:
02 June 2021 (online)

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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