Thrombus stiffness depends on occlusion site and influences thrombectomy outcomes in acute ischemic stroke

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Acute ischemic stroke undergoing endovascular thrombectomy (n=51). Intervention: Proximal M2 occlusion site and thrombus stiffness vs. M1 and ICA occlusion sites. Primary outcome: Thrombus stiffness (kPa) and modified first-pass reperfusion (mFPR, defined as eTICI score >=2b after the first EVT attempt) (MD -0.524 kPa (M2 vs M1), 95% CI -1.024 to -0.093).

Q: What does this research mean for the field?

Thrombi retrieved from distal vessels (proximal M2) are significantly softer than those from proximal intracranial arteries (M1 and ICA), and first-pass thrombectomy reperfusion success is markedly lower for both the stiffest ICA thrombi and the softest M2 thrombi compared to M1 thrombi. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Luca Bontempi; Janneke M. H. Cruts; Rachel M. E. Cahalane; Otilia E Ilie; Nikki Boodt; Daniël Bos; Behrooz Fereidoonnezhad; Pieter‐Jan van Doormaal; Aad van der Lugt; Diederik W.J. Dippel; Frank J H Gijsen

doi:10.1093/esj/aakag132

November 1, 2026European Stroke JournalOpen Access

Thrombus stiffness depends on occlusion site and influences thrombectomy outcomes in acute ischemic stroke

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Key result

Proximal M2 thrombi show ~0.52 kPa lower stiffness than M1 occlusions.

MD -0.524 kPa (M2 vs M1)
95% CI -1.024 to -0.093
n=51

Figures

Graphical abstract published by European Stroke Journal — Graphical abstract · Published by European Stroke Journal · CC BY

Why the study?

Only 60% of patients with acute ischemic stroke achieve successful reperfusion after the first endovascular thrombectomy attempt, and in vitro studies showed that thrombus stiffness influences retrieval efficacy. The clinical, imaging, and histological correlates of thrombus stiffness and its association with first-pass reperfusion required prospective investigation.

Does intracranial occlusion location determine thrombus stiffness, and how does thrombus stiffness influence modified first-pass reperfusion during endovascular thrombectomy in patients with acute ischemic stroke?

Key Points

Investigate how thrombus stiffness relates to occlusion location, clinical and imaging characteristics, and histological composition, and evaluate its association with endovascular thrombectomy success.
Prospective observational study analyzing 281 thrombus samples collected from 51 acute ischemic stroke patients undergoing endovascular thrombectomy.
Quantified thrombus stiffness via compressive mechanical testing, evaluated histological composition with tissue staining, and assessed radiological markers on non-contrast CT and CT angiography.
Modeled associations between stiffness, occlusion sites, and modified first-pass reperfusion using linear and logistic mixed-effects regression.
Thrombi retrieved from the proximal M2 segment had significantly lower stiffness (0.236 kPa, 95% CI, 0.136–0.409) than those from the M1 segment (0.760 kPa, 95% CI, 0.492–1.174) and internal carotid artery (1.106 kPa, 95% CI, 0.558–2.192).
Adjusted modified first-pass reperfusion rates were 40.4% (95% CI, 24.5–67.0) for internal carotid artery occlusions, 89.7% (95% CI, 79.5–97.0) for M1 occlusions, and 53.0% (95% CI, 30.8–84.7) for M2 occlusions.
Procedural complications occurred in 18% (9/51) of procedures, comprising embolic complications in 10% (5/51), significant vasospasm in 6% (3/51), and arterial dissection in 2% (1/51).

Study Design

Type

Observational (n=51)

Multicenter

No

Structured PICO

Does intracranial occlusion location determine thrombus stiffness, and how does thrombus stiffness influence modified first-pass reperfusion during endovascular thrombectomy in patients with acute ischemic stroke?

P

Population

51 adults (median age 77 years, 66.6% female) with acute ischemic stroke due to anterior circulation occlusion undergoing endovascular thrombectomy with 281 retrieved thrombus samples analyzed.

E

Exposure

Ex vivo compressive mechanical testing of retrieved thrombi (unconfined compression in DMEM at 37 °C within 6 hours of retrieval, measuring stiffness at 10% strain), histopathological staining (MSB for RBCs and fibrin/platelet aggregates; CD42b+ immunostaining for platelets), and pre-interventional NCCT/CTA imaging analysis across anterior circulation occlusion sites.

C

Comparator

Comparison across intracranial occlusion locations (ICA vs M1 vs proximal M2 segment of the middle cerebral artery) and across ranges of thrombus stiffness, radiological features, and histological composition.

O

Outcome

Ex vivo thrombus stiffness (kPa) and modified first-pass reperfusion (mFPR, defined as achieving an expanded Thrombolysis in Cerebral Infarction [eTICI] score ≥2b [50%–100% reperfusion] after the first EVT attempt, evaluated on digital subtraction angiography).surrogate

Main Result

Mean Difference: -0.524 (95% CI -1.024–-0.093)

Absolute Event Rate: 0.236% vs 0.76%

This study demonstrates that intracranial occlusion location is the strongest clinical predictor of ex vivo thrombus stiffness—with distal M2 clots being significantly softer than proximal M1 and ICA clots—and that both extreme stiffness in the ICA and extreme softness in the M2 segment are associated with reduced first-pass thrombectomy success.

Limitations

Ex vivo thrombi could only be obtained from successful EVT procedures, excluding those where thrombus retrieval was unsuccessful and potentially introducing selection bias.
Single-center observational study with a relatively small patient sample size (51 independent patient observations for outcome analysis).
Potential fibrinolysis-related effects on thrombus stiffness may have been attenuated due to delays between peripheral hospital IVT administration and mechanical testing.
External validation in an independent AIS cohort is lacking.
Selection bias as ex vivo thrombi can only be obtained from procedures where thrombus retrieval was successful, excluding the most resistant or unretrievable clots
Small effective sample size of 51 independent patients for the clinical outcome (GLMR) analysis, making outcome findings exploratory
Potential attenuation of intravenous thrombolysis (IVT) effects due to delays between peripheral hospital administration and ex vivo mechanical testing
Single-center cohort lacking external validation, with 43.3% of variance in thrombus stiffness remaining unexplained by the full mixed-effects model

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Implication

Occlusion site may guide EVT device trials; extends in vitro data but leaves open prospective validation before practice change.

Abstract

Introduction Only 60% of patients with acute ischemic stroke (AIS) achieve successful reperfusion after the first endovascular thrombectomy (EVT) attempt. In vitro studies have shown that thrombus stiffness influences thrombus-device interaction and retrieval efficacy. This prospective observational study investigates how thrombus stiffness relates to clinical factors, thrombus imaging characteristics and histological composition. It further explores the association between thrombus stiffness and EVT success, as measured by the modified first-pass reperfusion (mFPR). Patients and methods A total of 281 thrombus samples were collected from 51 AIS patients undergoing EVT. Thrombus stiffness was quantified using compressive mechanical testing, composition from histological staining and radiological characteristics from pre-interventional non-contrast computed tomography (CT) and CT angiography. Statistical analysis was performed using linear and logistic mixed-effects regression models. Results Thrombi retrieved from the proximal M2 segment of the middle cerebral artery showed significant lower stiffness (0.236 kPa, 95% CI, 0.136–0.409) compared to those from the M1 segment (0.760 kPa, 95% CI, 0.492–1.174) and from the ICA (1.106 kPa, 95% CI, 0.558–2.192). Occlusion location was the strongest clinical marker of thrombus stiffness. Adjusted mFPR probability was 40.4% (95% CI, 24.5–67.0) for thrombi retrieved from the ICA, 89.7% (95% CI, 79.5–97.0) for M1 occlusions, and 53.0% (95% CI, 30.8–84.7) for M2 occlusions. Conclusion Thrombi in distal vessels of the anterior cerebral circulation are significantly softer than those in proximal intracranial arteries. First-pass EVT success is lower for the stiffest thrombi from the ICA and for the softest thrombi from M2, providing a foundation for future biomechanically informed thrombus removal strategies to optimise AIS treatment.

Discussion

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Cite This Study

Bontempi et al. (2026) conducted an observational in Acute ischemic stroke undergoing endovascular thrombectomy (n=51). Proximal M2 occlusion site and thrombus stiffness vs. M1 and ICA occlusion sites was evaluated on Thrombus stiffness (kPa) and modified first-pass reperfusion (mFPR, defined as eTICI score >=2b after the first EVT attempt) (MD -0.524 kPa (M2 vs M1), 95% CI -1.024 to -0.093). Proximal M2 thrombi had lower stiffness (0.236 kPa) than M1 (0.760 kPa) and ICA (1.106 kPa), with lower mFPR in ICA (40.4%) and M2 (53.0%) vs M1 (89.7%).

synapsesocial.com/papers/6af3463ebdf2424ebd04f7ed https://doi.org/10.1093/esj/aakag132

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Thrombus stiffness depends on occlusion site and influences thrombectomy outcomes in acute ischemic stroke

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Thrombus stiffness depends on occlusion site and influences thrombectomy outcomes in acute ischemic stroke

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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