Modelling Combined Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischaemic Stroke: Understanding the Relationship between Stent Retriever Configuration and Clot Lysis Mechanisms

Background: Combined intravenous thrombolysis and mechanical thrombectomy (IVT-MT) is a common treatment in acute ischaemic stroke, however the interaction between IVT and MT from a physiological standpoint is poorly understood. In this pilot study, we conduct numerical simulations of combined IVT-MT with various idealised stent retriever configurations to evaluate performance in terms of complete recanalisation times and lysis patterns. Methods: A 3D patient-specific geometry of a terminal internal carotid artery with anterior and middle cerebral arteries is reconstructed, and a thrombus is artificially implanted in the MCA branch. Various idealised stent retriever configurations are implemented by varying stent diameter and stent placement, and a configuration without a stent retriever provides a baseline for comparison. A previously validated multi-level model of thrombolysis is used, which incorporates blood flow, drug transport, and fibrinolytic reactions within a fibrin thrombus. Results: Fastest total recanalisation was achieved in the thrombus without a stent retriever, with lysis times increasing with stent retriever diameter. Two mechanisms of clot lysis were established: axial and radial permeation. Axial permeation from the clot front was the primary mechanism of lysis in all configurations, as it facilitated increased protein binding with fibrin fibres. Introducing a stent retriever channel allowed for radial permeation, which occurred at the fluid-thrombus interface, although lysis was much slower in the radial direction because of weaker secondary velocities. Conclusions: Numerical models can be used to better understand the complex physiological relationship between IVT and MT. Two different mechanisms of lysis were established, providing a basis towards improving the efficacy of combined treatments.

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Mechanical thrombectomy in acute ischaemic stroke patients with pre-interventional intracranial haemorrhage following intravenous thrombolysis

The Neuroradiology Journal ◽

10.1177/19714009211009112 ◽

2021 ◽

pp. 197140092110091

Author(s):

Hanna Styczen ◽

Matthias Gawlitza ◽

Nuran Abdullayev ◽

Alex Brehm ◽

Carmen Serna-Candel ◽

...

Keyword(s):

Clinical Outcome ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Intracranial Haemorrhage ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Modified Rankin Scale ◽

Large Vessel Occlusion ◽

Stroke Patients ◽

Vessel Occlusion

Background Data on outcome of endovascular treatment in patients with acute ischaemic stroke due to large vessel occlusion suffering from intravenous thrombolysis-associated intracranial haemorrhage prior to mechanical thrombectomy remain scarce. Addressing this subject, we report our multicentre experience. Methods A retrospective analysis of consecutive acute ischaemic stroke patients treated with mechanical thrombectomy due to large vessel occlusion despite the pre-interventional occurrence of intravenous thrombolysis-associated intracranial haemorrhage was performed at five tertiary care centres between January 2010–September 2020. Baseline demographics, aetiology of stroke and intracranial haemorrhage, angiographic outcome assessed by the Thrombolysis in Cerebral Infarction score and clinical outcome evaluated by the modified Rankin Scale at 90 days were recorded. Results In total, six patients were included in the study. Five individuals demonstrated cerebral intraparenchymal haemorrhage on pre-interventional imaging; in one patient additional subdural haematoma was observed and one patient suffered from isolated subarachnoid haemorrhage. All patients except one were treated by the ‘drip-and-ship’ paradigm. Successful reperfusion was achieved in 4/6 (67%) individuals. In 5/6 (83%) patients, the pre-interventional intracranial haemorrhage had aggravated in post-interventional computed tomography with space-occupying effect. Overall, five patients had died during the hospital stay. The clinical outcome of the survivor was modified Rankin Scale=4 at 90 days follow-up. Conclusion Mechanical thrombectomy in patients with intravenous thrombolysis-associated intracranial haemorrhage is technically feasible. The clinical outcome of this subgroup of stroke patients, however, appears to be devastating with high mortality and only carefully selected patients might benefit from endovascular treatment.

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European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

European Stroke Journal ◽

10.1177/2396987321989865 ◽

2021 ◽

pp. 239698732198986

Author(s):

Eivind Berge ◽

William Whiteley ◽

Heinrich Audebert ◽

Gian Marco De Marchis ◽

Ana Catarina Fonseca ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Clinical Decision Making ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Late Time ◽

High Quality ◽

High Quality Evidence ◽

Consensus Statements ◽

Quality Evidence

Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.

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Stress hyperglycaemia is associated with poor functional outcomes in patients with acute ischaemic stroke after intravenous thrombolysis

QJM ◽

10.1093/qjmed/hcaa253 ◽

2020 ◽

Author(s):

J N Ngiam ◽

C W S Cheong ◽

A S T Leow ◽

Y -T Wei ◽

J K X Thet ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Functional Outcomes ◽

Mechanical Thrombectomy ◽

Venous Blood ◽

Intravenous Thrombolysis ◽

Glycated Haemoglobin ◽

Stress Hyperglycaemia ◽

As Stress

Summary Background Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as ‘stress hyperglycaemia’. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT). Methods We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3–6 at 3 months) after IVT. Results Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P < 0.001), male (70.7% vs. 51.5%, P < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59–9.09, P = 0.003). Conclusion SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.

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Mechanical thrombectomy after intravenous thrombolysis for acute ischaemic stroke

The Lancet Neurology ◽

10.1016/s1474-4422(16)30379-9 ◽

2017 ◽

Vol 16 (2) ◽

pp. 103-104 ◽

Cited By ~ 4

Author(s):

Nicola Morelli ◽

Eugenia Rota ◽

Emanuele Michieletti ◽

Donata Guidetti

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis

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Initial experience with the novel EmboTrap II clot-retrieving device for the treatment of ischaemic stroke

Interventional Neuroradiology ◽

10.1177/1591019918819709 ◽

2019 ◽

Vol 25 (3) ◽

pp. 271-276 ◽

Cited By ~ 3

Author(s):

Iacopo Valente ◽

Sergio Nappini ◽

Leonardo Renieri ◽

Alessandro Pedicelli ◽

Emilio Lozupone ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Artery Occlusion ◽

Large Artery ◽

The Novel ◽

Neurological Outcomes ◽

Stent Type ◽

Radiological Data

Introduction We report our experience with the novel stent-type clot-retrieval device EmboTrap II for the revascularization of large artery occlusions in acute ischaemic stroke. Materials and methods Twenty-nine patients with acute ischaemic stroke due to large artery occlusion underwent mechanical thrombectomy with the new EmboTrap II in two Italian centres. Clinical, procedural and radiological data were collected. Angiographic results and neurological outcomes were analysed. Results Only large vessel occlusions were included. Intravenous thrombolysis was administered in 72% of patients. Successful reperfusion (TICI 2b-3) was obtained in 76% of patients treated exclusively with EmboTrap II. No device-related permanent complications occurred. Conclusion In our experience, mechanical thrombectomy with EmboTrap II is safe and effective. Reperfusion rate was comparable to that obtained with other stent retrievers.

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Mechanical thrombectomy after intravenous thrombolysis for acute ischaemic stroke – Authors' reply

The Lancet Neurology ◽

10.1016/s1474-4422(16)30378-7 ◽

2017 ◽

Vol 16 (2) ◽

pp. 104 ◽

Cited By ~ 1

Author(s):

Serge Bracard ◽

Xavier Ducrocq ◽

Francis Guillemin ◽

Thierry Moulin ◽

Jean-Louis Mas

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis

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Mechanical thrombectomy for the treatment of acute ischaemic stroke following pulmonary lobectomy

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2019.0028 ◽

2019 ◽

Vol 101 (5) ◽

pp. e115-e118 ◽

Cited By ~ 1

Author(s):

JM Ali ◽

I Wolff ◽

F Falconieri ◽

G Aresu ◽

AS Coonar ◽

...

Keyword(s):

Quality Of Life ◽

Ischaemic Stroke ◽

Postoperative Complication ◽

Acute Ischaemic Stroke ◽

Mechanical Thrombectomy ◽

Cerebral Arteries ◽

Standard Of Care ◽

Artery Occlusion ◽

Pulmonary Lobectomy

Acute ischaemic stroke is a devastating postoperative complication that significantly impacts upon a patient’s quality of life. Endovascular retrieval of thromboembolic material from proximal cerebral arteries by mechanical thrombectomy is the new standard of care for patients presenting with a proximal artery occlusion. We report the case of a patient developing an acute ischaemic stroke following pulmonary lobectomy, who was transferred to the regional neurosciences unit, despite the absence of an established referral pathway, to undergo mechanical thrombectomy, with significant prognostic neurological benefit. We would advocate all cardiothoracic centres identify their regional neurosciences unit and initiate discussion to establish a referral pathway.

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Mathematical Modelling of Intravenous Thrombolysis in Acute Ischaemic stroke: Effects of Dose Regimens on Levels of Fibrinolytic Proteins and Clot Lysis Time

Pharmaceutics ◽

10.3390/pharmaceutics11030111 ◽

2019 ◽

Vol 11 (3) ◽

pp. 111 ◽

Cited By ~ 1

Author(s):

Boram Gu ◽

Andris Piebalgs ◽

Yu Huang ◽

Colin Longstaff ◽

Alun Hughes ◽

...

Keyword(s):

Mathematical Modelling ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Blood Clot ◽

Intravenous Thrombolysis ◽

Drug Dose ◽

Clot Lysis ◽

Bolus Infusion ◽

Increased Risk ◽

Fibrinolytic Proteins

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.

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