Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction

Rojano, Rodrigo Méndez; Mendez, Simon; Lucor, Didier; Ranc, Alexandre; Giansily‐Blaizot, Muriel; Schved, Jean‐François; Nicoud, Franck

doi:10.1007/s10237-019-01134-4

Cited by 20 publications

(25 citation statements)

References 57 publications

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“…As mentioned above, a more detailed representation of chemical activation (Hill-like activation and consideration of further chemical species) should be a next possible step. In addition, the influence of the coagulation cascade and the influence of artificial materials on platelet activation could be included, like in the model by Mendez et al 21 Validation of a numerical thrombosis model remains a tremendous challenge, as it is extremely difficult to obtain experimental data on thrombus formation in medical devices. Hence, computational studies about thrombus formation should be handled with care.…”

Section: Discussionmentioning

confidence: 99%

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps

Blum

Groß-Hardt²,

Steinseifer

et al. 2022

Cardiovasc Eng Tech

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Purpose Thrombosis ranks among the major complications in blood-carrying medical devices and a better understanding to influence the design related contribution to thrombosis is desirable. Over the past years many computational models of thrombosis have been developed. However, numerically cheap models able to predict localized thrombus risk in complex geometries are still lacking. The aim of the study was to develop and test a computationally efficient model for thrombus risk prediction in rotary blood pumps. Methods We used a two-stage approach to calculate thrombus risk. The first stage involves the computation of velocity and pressure fields by computational fluid dynamic simulations. At the second stage, platelet activation by mechanical and chemical stimuli was determined through species transport with an Eulerian approach. The model was compared with existing clinical data on thrombus deposition within the HeartMate II. Furthermore, an operating point and model parameter sensitivity analysis was performed. Results Our model shows good correlation (R2 > 0.93) with clinical data and identifies the bearing and outlet stator region of the HeartMate II as the location most prone to thrombus formation. The calculation of thrombus risk requires an additional 10–20 core hours of computation time. Conclusion The concentration of activated platelets can be used as a surrogate and computationally low-cost marker to determine potential risk regions of thrombus deposition in a blood pump. Relative comparisons of thrombus risk are possible even considering the intrinsic uncertainty in model parameters and operating conditions.

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Section: Discussionmentioning

confidence: 99%

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps

Blum

Groß-Hardt²,

Steinseifer

et al. 2022

Cardiovasc Eng Tech

View full text Add to dashboard Cite

show abstract

“…As already mentioned above, a more detailed representation of chemical activation (Hill-like activation and consideration of further chemical species) might be a next possible steps. In addition, influence of the coagulation cascade and the influence of artificial materials on platelet activation could be included, like in the model by Mendez et al [34].…”

Section: Discussionmentioning

confidence: 99%

An accelerated thrombosis model for computational fluid dynamics simulations in rotary blood pumps

Blum¹,

Groß-Hardt²,

Steinseifer³

et al. 2021

Preprint

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Thrombosis is one of the major complications in blood-carrying medical devices and a better understanding to influence design of such devices is desirable. Over the past years many computational models of thrombosis have been developed. However, open questions remain about the applicability and implementation within a pump development process. The aim of the study was to develop and test a computationally efficient model for thrombus risk prediction in rotary blood pumps. We used a two-stage approach to calculate thrombus risk. At the first stage, the velocity and pressure fields were computed by computational fluid dynamic (CFD) simulations. At the second stage, platelet activation by mechanical and chemical stimuli was determined through species transport with an Eulerian approach. The model was implemented in ANSYS CFX and compared with existing clinical data on thrombus deposition within the HeartMate II. Our model shows good correlation (R2>0.94) with clinical data and identifies the bearing and outlet stator region of the HeartMate II as the location most prone to thrombus formation. The calculation of platelet activation requires an additional 10-20 core hours of computation time. The concentration of activated platelets can be used as a surrogate marker to determine risk regions of thrombus deposition in a blood pump. Model expansion, e.g. by including more chemical species can easily be performed. We make our model openly available by implementing it for the FDA benchmark blood pump.

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“…This reduced-order scheme economized computational time by using a minimal number of biochemical species. 34 The hallmark model of Hockin et al 35 was used here as a reference to calibrate the reduced model. Least square optimization was performed with the Python module S-timator (https:// webpa ges.cienc ias.ulisb oa.pt/~aefer reira/ stima tor/) to identify parameters that best fit the numerical data of Hockin et al (See Table 2).…”

Section: Coagulation Reactions Triggered By Tissue Factormentioning

confidence: 99%

Multi‐constituent simulation of thrombus formation at LVAD inlet cannula connection: Importance of Virchow’s triad

2021

Self Cite

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As pump thrombosis is reduced in current‐generation ventricular assist devices (VAD), adverse events such as bleeding or stroke remain at unacceptable rates. Thrombosis around the VAD inlet cannula (IC) has been highlighted as a possible source of stroke events. Recent computational fluid dynamics (CFD) studies have attempted to characterize the thrombosis risk of different IC‐ventricle configurations. However, purely CFD simulations relate thrombosis risk to ad hoc criteria based on flow characteristics, with little consideration of biochemical factors. This study investigates the genesis of IC thrombosis including two elements of the Virchow's triad: endothelial injury and hypercoagulability. To this end a multi‐scale thrombosis simulation that includes platelet activity and coagulation reactions was performed. Our results show significant thrombin formation in stagnation regions (|u| < 0.005 m/s) close to the IC wall. In addition, high shear‐mediated platelet activation was observed over the leading‐edge tip of the cannula. The current study reveals the importance of biochemical factors to the genesis of thrombosis at the ventricular‐cannula junction in a perioperative state. This study is a first step toward the long‐term objective of including clinically relevant pharmacological kinetics such as heparin or aspirin in simulations of inflow cannula thrombosis.

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Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction

Cited by 20 publications

References 57 publications

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps

An accelerated thrombosis model for computational fluid dynamics simulations in rotary blood pumps

Multi‐constituent simulation of thrombus formation at LVAD inlet cannula connection: Importance of Virchow’s triad

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