Device Thrombogenicity Emulation: An In Silico Predictor of In Vitro and In Vivo Ventricular Assist Device Thrombogenicity

Wei Che Chiu, Phat L. Tran, Zain I Khalpey, Eric Lee, Yi Ren Woo, Marvin J Slepian, Danny Bluestein

Research output: Contribution to journalArticle

Abstract

Ventricular assist devices (VAD), a mainstay of therapy for advanced and end-stage heart failure, remain plagued by device thrombogenicity. Combining advanced in silico and in vitro methods, Device Thrombogenicity Emulation (DTE) is a device design approach for enhancing VAD thromboresistance. Here we tested DTE efficacy in experimental VAD designs. DTE incorporates iterative design modifications with advanced CFD to compute the propensity of large populations of platelets to activate by flow-induced stresses (statistically representing the VAD ‘Thrombogenic Footprint’). The DTE approach was applied to a VAD (MIN DTE ) design with a favorable thromboresistance profile and compared against a design (MAX DTE ) that generated an intentionally poor thromboresistance profile. DTE predictions were confirmed by testing physical prototypes in vitro by measuring VAD thrombogenicity using the modified prothrombinase assay. Chronic in vivo studies in VAD implanted calves, revealed MIN DTE calf surviving well with low platelet activation, whereas the MAX DTE animal sustained thromboembolic strokes. DTE predictions were confirmed, correlating with in vitro and in vivo thrombogenicity, supporting utility in guiding device development, potentially reducing the need for animal studies.

Original languageEnglish (US)
Article number2946
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Heart-Assist Devices
Computer Simulation
Equipment and Supplies
Equipment Design
In Vitro Techniques
Platelet Activation
Thromboplastin
Blood Platelets
Heart Failure
Stroke

ASJC Scopus subject areas

  • General

Cite this

Device Thrombogenicity Emulation : An In Silico Predictor of In Vitro and In Vivo Ventricular Assist Device Thrombogenicity. / Chiu, Wei Che; Tran, Phat L.; Khalpey, Zain I; Lee, Eric; Woo, Yi Ren; Slepian, Marvin J; Bluestein, Danny.

In: Scientific reports, Vol. 9, No. 1, 2946, 01.12.2019.

Research output: Contribution to journalArticle

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