# Contact Pathway Activation on Vascular Devices

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $743,402

## Abstract

Project Summary
This project evaluates the contribution of contact activation to the progression of vascular device-related
blood coagulation and thrombus formation. The research will generate new knowledge supporting the
development of novel anticoagulants that lack dose-limiting toxicity, are significantly safer, and cause less
bleeding than current drugs while also helping to identify medical conditions that could benefit from the
therapeutic use of these contact activation inhibitors.
Vascular devices such as stents, hemodialyzers and oxygenators can activate blood and often require the
use of systemic antithrombotics to reduce the incidence or severity of device failure and thrombotic
events. Currently marketed antithrombotic drugs can help reduce clot formation on vascular devices, but
all increase the risk of bleeding. For instance, 30% of severely ill neonates that are treated with
extracorporeal membrane oxygenation (ECMO) experience severe bleeding complications, including
gastrointestinal, pulmonary and brain hemorrhage, which contribute to the high mortality rate of neonatal
ECMO. These and other vascular device-associated thrombotic and treatment-associated bleeding
complications signify the unmet medical need to improve the safety and outcome of vascular interventions,
including permanent intravascular devices like stents and various forms of temporal extracorporeal organ
support (ECOS). This project aims at identifying and characterizing the molecular mechanisms that drive
propagation of vascular device surfaces-initiated thrombus formation under flow. Our preliminary data now
suggest that coagulation factors (F)XII and XI of the contact activation pathway play important roles in not
only the initiation but also the propagation of the thrombotic process. We focus on FXII and FXI because
(1) there appears to be a causal relationship between contact activation and vascular device failure, and
(2) targeting the contact activation pathway as a therapeutic approach is less likely to have detrimental
bleeding side effects for patients. Each Aim will have 3 subaims that will translate our (A) molecular
mechanistic in vitro studies to (B) ex vivo blood flow studies of artificial surface-related thrombus formation
and (C) in vivo studies of vascular device-related thrombus propagation in primate models.
The potential significance of this translational project is that the knowledge generated will lead to
verification of promising, safe, and druggable molecular targets within the contact activation pathway to
both prevent and interrupt vascular device-related thrombosis. Our research may ultimately support the
rationale for the development of selective contact activation inhibitors that could benefit a large number of
patients exposed to vascular interventions and devices.

## Key facts

- **NIH application ID:** 10198027
- **Project number:** 5R01HL144113-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Monica T Hinds
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $743,402
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198027

## Citation

> US National Institutes of Health, RePORTER application 10198027, Contact Pathway Activation on Vascular Devices (5R01HL144113-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198027. Licensed CC0.

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