# Impact of turbulence on blood in mechanical circulatory support

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $426,943

## Abstract

PROJECT SUMMARY/ABSTRACT
 Mechanical circulatory support (MCS) is a critical tool to treat heart or lung failure, in the form of
extracorporeal circulation through membrane oxygenation or through a ventricular assist device.
Thrombosis and bleeding remain major complications with MCS. As a result, patients receive systemic
anticoagulation to prevent thrombosis. However, this can increase the risk for bleeding, which is the
most common complication in MCS. To counter this issue, there has been a large effort to eliminate or
minimize the need for anticoagulation. Surprisingly, even if anticoagulation is eliminated, studies
demonstrate that bleeding remains highly prevalent, while thrombosis remains relatively unaffected.
Therefore, there is a need to focus on alternative pathways to bleeding. Almost all patients on MCS
experience the bleeding disorder acquired von Willebrand syndrome. Furthermore, patients, especially
pediatric patients, experience platelet dysfunction and can exhibit low platelet counts. We attribute
these events to the flow environment in MCS. While many groups have focused on the effect of shear
stress on blood, our group discovered an unprecedented role for turbulence in driving loss of high and
even intermediate molecular weight von Willebrand factor (VWF) multimers, reducing the ability for
VWF to bind to platelets and to collagen. Furthermore, there is strong evidence that flow in MCS is
causing signals for platelet activation, but also clearance and cell death, with an unknown effect of
turbulence. The combination of signals in response to flow can lead to both thrombosis and hemorrhage,
depending on the balance of events. Our goal is identify what specific conditions lead to VWF or platelet
functional loss in response to flow by pursuing three aims. 1) We will quantify changes in thrombus
growth in response to turbulence relative to laminar shear conditions for various anticoagulants. 2) We
will quantify the increased cleavage occurring in turbulence relative to laminar flow for similar shear
stress conditions and how VWF function varies after flow exposure with and without flow-induced
extension. 3) We will assess platelet state after exposure to different flow regimes and how this changes
with the presence of VWF or with potential new therapeutic targets. Altogether, this work will distinguish
the impact of turbulence relative to shear stress on blood, which could lead to improved design criteria
for blood-contacting medical devices and potential therapeutics if we identify specific pathways leading
to dysfunctional hemostasis.

## Key facts

- **NIH application ID:** 10497656
- **Project number:** 1R01HL164424-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David Bark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $426,943
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497656

## Citation

> US National Institutes of Health, RePORTER application 10497656, Impact of turbulence on blood in mechanical circulatory support (1R01HL164424-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10497656. Licensed CC0.

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