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

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 111 ◽  
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.

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

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1271
Author(s):  
Emily Louise Manchester ◽  
Dylan Roi ◽  
Boram Gu ◽  
Xiao Yun Xu ◽  
Kyriakos Lobotesis
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Drug Transport ◽  
Mechanical Thrombectomy ◽  
Numerical Models ◽  
Cerebral Arteries ◽  
Intravenous Thrombolysis ◽  
Stent Retriever ◽  
Patient Specific ◽  
Clot Lysis

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.

Carotid endarterectomy following thrombolysis for acute ischaemic stroke

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 116-120 ◽  
Author(s):  
Naz Ahmed ◽  
Damian Kelleher ◽  
Manmohan Madan ◽  
Sarita Sochart ◽  
George A. Antoniou
Keyword(s):  
Ischaemic Stroke ◽  
Carotid Endarterectomy ◽  
Acute Ischaemic Stroke ◽  
Intravenous Thrombolysis ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Wound Complications ◽  
Cardiac Complications ◽  
High Dependency ◽  
Low Incidence

Abstract. Background: Insufficient evidence exists to support the safety of carotid endarterectomy (CEA) following intravenous thrombolysis (IVT) for acute ischaemic stroke. Our study aimed to report a single-centre experience of patients treated over a five-year period. Patients and methods: Departmental computerised databases were interrogated to identify patients who suffered an ischaemic stroke and subsequently underwent thrombolysis followed by CEA. Mortality and stroke within 30 days of surgery were defined as the primary outcome end points. Results: Over a five-year period, 177 out of a total of 679 carotid endarterectomies (26 %) were performed in patients presenting with acute ischaemic stroke. Twenty-five patients (14 %) received IVT prior to CEA in the form of alteplase. Sixty percent of patients were male with a mean age of 68 years. Sixteen patients (64 %) underwent CEA within 14 days of IVT and the median interval between thrombolysis and CEA was 7.5 days (range, 3–50 days). One female patient died of a further intraoperative stroke within 30 days of surgery, yielding a mortality rate of 4 %. Two patients (8 %) suffered from cardiac complications postoperatively resulting in a short high dependency unit stay. Another two patients (8 %) developed local wound complications, which were managed conservatively without the need for re-operation. The median hospital length of stay was 4.5 days (range, 1–33 days). Conclusions: Our experience indicates that CEA post-thrombolysis has a low incidence of mortality. Further high quality evidence is required before CEA can be routinely recommended following IVT for acute ischaemic stroke.

scholarly journals Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e045559
Author(s):  
Xuelei Zhang ◽  
Anxin Wang ◽  
Jing Yu Zhang ◽  
Baixue Jia ◽  
Xiaochuan Huo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Endovascular Treatment ◽  
Functional Outcome ◽  
Acute Ischaemic Stroke ◽  
Controlled Trial ◽  
Intravenous Thrombolysis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ischaemic Injury ◽  
Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

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

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.

Obesity in acute ischaemic stroke patients treated with intravenous thrombolysis therapy

2021 ◽  
pp. 1-8
Author(s):  
Hongmin Li ◽  
Suliman Khan ◽  
Rabeea Siddique ◽  
Qian Bai ◽  
Yang Liu ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
Thrombolysis Therapy

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

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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