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Impact of turbulence on blood in mechanical circulatory support

Award Number: R01HL164424
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Impact of turbulence on blood in mechanical circulatory support - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $23,322 )
2026	2026	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Blood Diseases and Resources Research	002	5	8/14/2026	NON-COMPETING CONTINUATION	$376,108
2026	2025	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Blood Diseases and Resources Research	001	4	4/10/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2026	2024	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Blood Diseases and Resources Research	000	3	2/18/2026	NON-COMPETING CONTINUATION	-$352,787
														Subtotal = $23,322

Issue Date FY: 2025 ( Subtotal = $381,946 )
2025	2025	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Blood Diseases and Resources Research	001	4	9/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$381,946
2025	2024	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Blood Diseases and Resources Research	000	3	9/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $381,946

Issue Date FY: 2024 ( Subtotal = $413,092 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Blood Diseases and Resources Research	000	3	7/2/2024	NON-COMPETING CONTINUATION	$413,092
														Subtotal = $413,092

Issue Date FY: 2023 ( Subtotal = $421,522 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Blood Diseases and Resources Research	000	2	6/7/2023	NON-COMPETING CONTINUATION	$421,522
														Subtotal = $421,522

Issue Date FY: 2022 ( Subtotal = $426,943 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Blood Diseases and Resources Research	000	1	6/3/2022	NEW	$426,943
														Subtotal = $426,943

Grand Total All Awards = $1,666,825

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Impact of turbulence on blood in mechanical circulatory support

Award Number: R01HL164424

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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