Device thrombogenicity emulation: A novel methodology for optimizing the thromboresistance of cardiovascular devices

Danny Bluestein, Shmuel Einav, Marvin J Slepian

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers-before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase-achieving minimization of the device thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.

Original languageEnglish (US)
Pages (from-to)338-344
Number of pages7
JournalJournal of Biomechanics
Volume46
Issue number2
DOIs
StatePublished - Jan 18 2013

Fingerprint

Platelets
Equipment and Supplies
Hemodynamics
Coagulation
Shearing
Chemical activation
Computer simulation
Blood Platelets
Costs
Technology
Platelet Activation

Keywords

  • Blood flow
  • Device optimization
  • Device thrombogenicity emulation (DTE)
  • Mechanical circulatory support (MCS)
  • Platelets
  • Thrombogenicity
  • Ventricular assist devices (VAD)

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

Device thrombogenicity emulation : A novel methodology for optimizing the thromboresistance of cardiovascular devices. / Bluestein, Danny; Einav, Shmuel; Slepian, Marvin J.

In: Journal of Biomechanics, Vol. 46, No. 2, 18.01.2013, p. 338-344.

Research output: Contribution to journalArticle

@article{230768f7bbd14805a6f1559c755578b3,
title = "Device thrombogenicity emulation: A novel methodology for optimizing the thromboresistance of cardiovascular devices",
abstract = "Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers-before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase-achieving minimization of the device thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.",
keywords = "Blood flow, Device optimization, Device thrombogenicity emulation (DTE), Mechanical circulatory support (MCS), Platelets, Thrombogenicity, Ventricular assist devices (VAD)",
author = "Danny Bluestein and Shmuel Einav and Slepian, {Marvin J}",
year = "2013",
month = "1",
day = "18",
doi = "10.1016/j.jbiomech.2012.11.033",
language = "English (US)",
volume = "46",
pages = "338--344",
journal = "Journal of Biomechanics",
issn = "0021-9290",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Device thrombogenicity emulation

T2 - A novel methodology for optimizing the thromboresistance of cardiovascular devices

AU - Bluestein, Danny

AU - Einav, Shmuel

AU - Slepian, Marvin J

PY - 2013/1/18

Y1 - 2013/1/18

N2 - Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers-before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase-achieving minimization of the device thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.

AB - Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers-before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase-achieving minimization of the device thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.

KW - Blood flow

KW - Device optimization

KW - Device thrombogenicity emulation (DTE)

KW - Mechanical circulatory support (MCS)

KW - Platelets

KW - Thrombogenicity

KW - Ventricular assist devices (VAD)

UR - http://www.scopus.com/inward/record.url?scp=84872601869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872601869&partnerID=8YFLogxK

U2 - 10.1016/j.jbiomech.2012.11.033

DO - 10.1016/j.jbiomech.2012.11.033

M3 - Article

C2 - 23219278

AN - SCOPUS:84872601869

VL - 46

SP - 338

EP - 344

JO - Journal of Biomechanics

JF - Journal of Biomechanics

SN - 0021-9290

IS - 2

ER -