Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Multimeric Structural Degradation of vWF in Turbulent Flows

Award Number: R01HL166334
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/05/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Multimeric Structural Degradation of vWF in Turbulent Flows - ABSTRACT Acquired von Willebrand Syndrome (AvWS) characterized by the loss of high molecular weight multimers (HMWMs) of von Willebrand factor (vWF) is often associated with nonphysiologic blood flows. AvWS is found in patients with severe aortic stenosis (AS) or continuous-flow left ventricular assist devices (cf-LVADs). Interestingly, this hemostatic abnormality associated with severe AS is fully corrected on the first day after surgery. For AvWS associated with cf-LVADs, it disappears quickly after removal of the device, strongly suggesting that the device itself is responsible for the syndrome. It is widely believed that the supraphysiologic shear stress and/or long exposure time in severe AS and cf-LVADs are responsible for the loss of HMWM. Although the destruction of HMWM is believed to be a combination of mechanical and enzymatic cleavage, the complete mechanism still remains unclear. Also notable is that AvWS is rarely observed in pulsatile blood flow devices. There is a need to understand the degradation mechanism of vWF and exposure time especially when nonphysiologic blood flows are expected. The objective of this proposal is to characterize the degradation of HMWM under fully controlled laminar through turbulent blood flow conditions in terms of power density (energy dissipation rate per unit mass) and clinically relevant exposure times. The central hypothesis is that the degradation of HMWM of vWF is a time-sensitive mechanoenzymatic event that occurs primarily under turbulent flow conditions by exposing the ADAMTS13 to cleavage sites on vWF. Based on our previous publications as well as evidence in the literature, we believe that the majority of vWF multimer degradation is ADAMTS13 mediated. However, we recognize that there are other potential sinks and sources of vWF including adsorption to the surfaces of a device, binding to platelets, and release of vWF from ⍺-granules of activated platelets. We will test and account for these sinks and sources in these experiments. Successful completion of the proposed study will allow us to i) determine the relationship between nonphysiologic blood flow and exposure time involved in the loss of HMWM in cf-LVADs, ii) evaluate the degradation mechanism of HMWM, and iii) characterize the mechanism in terms of mechanoenzymatic, mechanistic, and enzymatic sensitivity through comprehensive vWF biology. Ultimately, the prospective model is expected to be a tool for device design optimization leading to a next-generation blood pump and better clinical outcomes for patients with AvWS.


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 = $500,715 )
2026	2026	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	001	4	3/24/2026	NON-COMPETING CONTINUATION	$15,327
2026	2026	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	4	2/11/2026	NON-COMPETING CONTINUATION	$485,388
														Subtotal = $500,715

Issue Date FY: 2025 ( Subtotal = $643,325 )
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	3	11/28/2024	NON-COMPETING CONTINUATION	$578,994
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	001	3	1/28/2025	NON-COMPETING CONTINUATION	$0
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	002	3	9/1/2025	NON-COMPETING CONTINUATION	$64,331
														Subtotal = $643,325

Issue Date FY: 2024 ( Subtotal = $628,507 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	2	11/27/2023	NON-COMPETING CONTINUATION	$577,201
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	001	2	6/12/2024	NON-COMPETING CONTINUATION	$51,306
														Subtotal = $628,507

Issue Date FY: 2023 ( Subtotal = $664,971 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	1	1/5/2023	NEW	$664,971
														Subtotal = $664,971

Grand Total All Awards = $2,437,518

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Multimeric Structural Degradation of vWF in Turbulent Flows

Award Number: R01HL166334

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/05/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer