# Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2020 · —

## Abstract

This CSR&D VA Career Development Award (CDA-2) will develop Dr. Khanh Nguyen as a
vascular surgeon-scientist trained in both basic and translational research approaches to study
vascular disease and apply discoveries to improve the care of patients. With the support of an
excellent mentorship team at the VA Portland Health Care System (VAPORHCS) and Oregon Health
& Science University (OHSU) headed by her primary mentor, Dr. Edward Neuwelt, she will study
deep vein thrombosis (DVT), where clots form in the deep veins of the body. Despite modern medical
treatment, chronic or recurrent DVT and post thrombotic syndrome (PTS), where signs and
symptoms of DVT persist or worsen causing lifelong disability. Recent clinical trials have shown that
even with the addition of catheter directed thrombolysis to standard anticoagulation therapy, PTS still
occurs. Anticoagulation treatment, primarily with warfarin or direct oral anticoagulants (DOAC) such
as rivaroxaban or apixaban, are inadequate to prevent PTS, although some early studies suggest that
the DOAC rivaroxaban may decrease the incidence of PTS but does not eliminate it.
 The goal of this proposal is to understand the process of inflammation and fibrosis in DVT
resolution. During DVT healing, these processes may be beneficial by directing tissue remodeling and
dissolving thrombus but may be detrimental by damaging vein walls, valves and surrounding tissues;
thereby leading PTS. Aim 1 of this proposal will examine the role of relaxin (RLX), that has anti-
inflammatory and anti-fibrotic effects in other vascular diseases, on the molecular, structural and
biomechanical changes of the thrombus and vein wall during DVT resolution using advanced
molecular, immunohistochemical, biomechanical and in-vivo imaging techniques including a novel
contrast, ferumoxytol enhanced-Magnetic Resonance Imaging (Fe-MRI). We will use in-vivo mouse
models of DVT, transgenic mice with deficiency in RLX (RLX -/-) under anticoagulant conditions
(warfarin versus rivaroxaban). Aim 2 will study the incidence of PTS defined by the clinical Villalta
score in patients after acute proximal lower extremity DVT that have been randomized to either
standard warfarin or rivaroxaban and explore RLX as a plasma biomarker and Fe-MRI as a
radiographic biomarker in a small, double blinded, randomized, controlled trial. RLX's potential as an
effective anti-inflammatory or anti-fibrotic makes it a promising therapeutic agent for preventing PTS.
 This award will provide the support for Dr. Nguyen to develop expertise in: (1) advanced molecular
and imaging techniques including ultrasound (US), Fe-MRI and in-vivo molecular imaging, (2) pre-
clinical approaches and models, (3) training in advanced patient-oriented research including research
design, implementation and biostatistics, and (4) professional academic training including
management and leadership. To achieve these goals, Dr. Nguyen has assembled a diverse and
multidisciplinary team of phys...

## Key facts

- **NIH application ID:** 9666570
- **Project number:** 1IK2CX001720-01A1
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Khanh P. Nguyen
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9666570

## Citation

> US National Institutes of Health, RePORTER application 9666570, Mechanisms of Deep Vein Thrombosis (DVT) and Vein Wall Fibrosis (1IK2CX001720-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9666570. Licensed CC0.

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