Thrombolysis: Observations and numerical models

Petkantchin, Rémy; Padmos, Raymond M.; Boudjeltia, Karim Zouaoui; Raynaud, Franck; Chopard, Bastien

doi:10.1016/j.jbiomech.2021.110902

Cited by 6 publications

(5 citation statements)

References 44 publications

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“…What further complicates the modeling is that one cell type can have completely opposite effects on fibrinolysis. We have recently shown that platelets can have a profibrinolytic or antifibrinolytic action depending on the clinical situation of the patients 6 . Numerical experimentation will be a complementary tool to address these issues.…”

Section: Discussionmentioning

confidence: 99%

“…This agent, typically tissue-Plasminogen-Activator (tPA), binds to the fibrin fibers to facilitate the conversion of plasminogen to plasmin, which will then cut the fibrin strands and result in thrombus breakdown. Although the biochemistry of fibrinolysis is well understood 5 , our knowledge of many aspects of the complete process in vivo and in vitro remains sparse 6 , 7 . For example, the permeability of the thrombus, which is central to the transport of active macromolecules in the bloodstream, is only estimated via indirect measurements like perviousness 8 ; the exact amount of drug that reaches the thrombus is unknown; even the dynamics of fibrin strands degradation is still actively investigated 9 – 14 .…”

Section: Introductionmentioning

confidence: 99%

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A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

Petkantchin,

Rousseau,

Eker

et al. 2023

Sci Rep

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One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

Petkantchin,

Rousseau,

Eker

et al. 2023

Sci Rep

Self Cite

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“…The molecular makeup of flavonoids determines how effective they are as antioxidants. 7 A lot of work has gone into finding and developing natural compounds with antiplatelet, anticoagulant, antithrombotic, and thrombolytic activities from various plant and animal sources. Epidemiologic research has shown that foods with an antithrombotic effect that has been experimentally proven can lower the risk of thrombosis.…”

Section: Introductionmentioning

confidence: 99%

In-vitro Evaluation of Antithrombin and Thrombolytic Activity of Leaves Extract of Lantana camara Linn

Mujbaile¹,

Khobragade²,

Mundhada³

2023

IJPQA

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Thrombosis is possible outcomes of excessive coagulation or inhibition of anticoagulant processes. The pathophysiology of thrombosis is primarily caused by irregularities of the vascular wall, changes in blood flow, and changes in blood composition. Now a day’s, various natural antithrombotic or thrombolytic medications are used for the treatment. This study evaluated the pharmacognostical, antithrombin and thrombolytic activity of leaves extract of plant Lantana camara. The extractive value of leaves extract of plant L. camara was higher (20.58%) in methylene chloride as solvent. Total ash of plant L. camara was about 9.00% w/w. In comparison with heparin L. camara extract shown 50.10, 60.23, 62.32, 68.48 and 71.32% antithrombin activity at 10, 20, 40, 60, 80 and 100 mg/mL concentration, respectively. When different extract concentrations were added in the tubes containing blood clots, L. camara showed a good thrombolytic activity. We conclude that the leaves extract of plant L. camara shows significant antithrombin and thrombolytic activity.

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“…Thrombolysis [2] and thrombectomy [1] revolutionised stroke treatment but up to 66% of patients remain functionally dependent [3,4]. The IN Silico clinical trials for the treatment of acute Ischaemic STroke (INSIST) consortium [5,6] set out to improve existing stroke treatments based on computational models [7][8][9][10][11]. In AIS, perfusion shortage is the primary driver of infarct formation associated with irreversible brain tissue and function loss.…”

Section: Introductionmentioning

confidence: 99%

MRI-based computational model generation for cerebral perfusion simulations in health and ischaemic stroke

Jozsa

Petr

Barkhof

et al. 2022

Preprint

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Cerebral perfusion models were found to be promising research tools to predict the impact of acute ischaemic stroke and related treatments on cerebral blood flow (CBF) linked to patients' functional outcome. To provide insights relevant to clinical trials, perfusion simulations need to become suitable for group-level investigations, but computational studies to date have been limited to a few patient-specific cases. This study set out to overcome issues related to automated parameter inference, that restrict the sample size of perfusion simulations, by integrating neuroimaging data. Seventy-five brain models were generated using measurements from a cohort of 75 healthy elderly individuals to model resting state CBF distributions. Computational perfusion model geometries were adjusted using healthy reference subjects' T1-weighted MRI. Haemodynamic model parameters were determined from CBF measurements corresponding to arterial spin labelling perfusion MRI. Thereafter, perfusion simulations were conducted for 150 acute ischaemic stroke cases by simulating an occlusion and cessation of blood flow in the left and right middle cerebral arteries. The anatomical (geometrical) fitness of the brain models was evaluated by comparing the simulated grey and white matter (GM and WM) volumes to measurements in healthy reference subjects. Statistically significant, strong positive correlations were found in both cases (GM: Pearson's r 0.74, P-value< 0.001; WM: Pearson's r 0.84, P-value< 0.001). Haemodynamic parameter tuning was verified by comparing total volumetric blood flow rate to the brain in reference subjects and simulations resulting in Pearson's r 0.89, and P-value< 0.001. In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based proxy was 197±25 ml. Computational results showed excellent agreement with anatomical and haemodynamic literature data corresponding to T1-weighted, T2-weighted, and phase-contrast MRI measurements both in healthy scenarios and in acute ischaemic stroke cases. Simulation results represented solely worst-case stroke scenarios with large infarcts because compensatory mechanisms, e.g. collaterals, were neglected. The established computational brain model generation framework provides a foundation for population-level cerebral perfusion simulations and for in silico clinical stroke trials which could assist in medical device and drug development.

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Thrombolysis: Observations and numerical models

Cited by 6 publications

References 44 publications

A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

In-vitro Evaluation of Antithrombin and Thrombolytic Activity of Leaves Extract of Lantana camara Linn

MRI-based computational model generation for cerebral perfusion simulations in health and ischaemic stroke

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