Focusing on Inflammation to Treat DVT Clots, Without Adverse Bleeding

A 25-year journey leads to the first calf vein thrombosis patients treated with a selectin inhibitor strategy.

7:00 AM

Author | Haley Otman

Targeting inflammation could be important to reducing morbidity and mortality in venous thromboembolism, a serious diagnosis that up to 900,000 Americans will receive annually, according to a Michigan Medicine team.

MORE FROM THE LAB: Sign up for our weekly newsletter

Thomas Wakefield, M.D., and Sumi Sood, M.D., recently tested a selectin inhibitor in normal volunteers and then treated calf vein thrombosis (deep vein thrombosis found below the knee) with the selectin inhibitor strategy to target inflammation. It's a global first, and the next step in their longtime National Institutes of Health-funded research.

"This has been a 25-year odyssey from the basic concept to the first-in-human clinical usage of the drug, and it worked well in the first patients," says Wakefield, head of vascular surgery and a director of Michigan Medicine's Frankel Cardiovascular Center.

Patients with DVT, or blood clots in the veins, are at risk of pulmonary embolism, in which a piece of the clot breaks loose and travels to the lungs, as well as recurrent DVT, extension of their DVT, and pain and swelling in the leg after DVT, the so-called post-thrombotic syndrome. They are typically put on blood thinners, but blood thinners also come with a bleeding risk.

"Our goal was to stop clotting without increasing the bleeding complications," says Sood, a Michigan Medicine hematologist and assistant professor in internal medicine and surgery.

Wakefield says the interplay between inflammation and thrombosis is significant.

"We now know it's a vicious cycle: The clots in the veins lead to inflammation, which leads to more clotting and then vein wall changes," he says.

The 25-year odyssey

Wakefield and his team started studying different formulations of P-selectin inhibitors in the early 1990s, finding they worked well to inhibit thrombosis in rodent and primate models.

In 2008, Wakefield and Denisa Wagner, M.D., of Harvard University, shared a five-year, $3.7 million grant from the NIH to partner with biopharmaceutical company Archemix to work toward clinical application of VTE treatment, starting with basic laboratory studies to understand the biology of the condition and identify which drugs had potential.

"We found P-selectin inhibitors are a way to inhibit the clotting and the inflammation that occurs in the vein," Wakefield says.

And in 2014, Wakefield and Sood received NIH funding through the National Heart, Lung, and Blood Institute's VITA program to treat clinical DVT for the first time with this anti-inflammatory approach. VITA, short for vascular interventions/innovations and therapeutic advances, helps accelerate promising therapies for underserved medical needs.

"We found an E-selectin inhibitor that was ready for trial and confirmed it worked as well as the P-selectin inhibitors," Wakefield says.

Calf vein DVT

Wakefield and Sood's team selected subjects with calf vein DVT, based on the current clinical approach.

SEE ALSO: Can Cancer Cause Blood Clots?

"Not all physicians feel all patients with calf vein DVT should be treated with anticoagulants, as the incidence of post-thrombotic syndrome is less when below the knee," Wakefield says.

Sood says calf vein DVT was also a good choice because more than half of DVTs involve the calf to some degree.

"It was a safer population to study than those with clots from the knee up, but a good population for studying venous thrombosis," Sood says. "Patients develop pain and swelling in their leg and are at risk of developing post-thrombotic syndrome."

Continuing the process

The patients treated so far have had positive results. Researchers hope the next step will be a multicenter trial with a combination of the selectin inhibitor strategy and standard therapy or this drug alone.

"Our contract has now ended with this proof of concept and initial foray into understanding how these drugs could work," Wakefield says. The next contract, VITA 2, will last until 2018 and is co-headed by Daniel D. Myers, DVM, MPH, and Wakefield. "Being able to reduce bleeding events could eventually be important to all sorts of clinical situations where you need an anticoagulant."

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure: Wakefield: Decision Resources Group


More Articles About: Rounds Deep Vein Thrombosis (DVT) Cardiovascular: Diseases & Conditions
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories Microscopic image of bone marrow with pink and white hues
Health Lab
Novel risk score for cardiovascular complications after bone marrow transplant
More bone marrow transplants, also known as hematopoietic stem cell transplantation, are being offered to older patients, a population at greater risk of cardiovascular disease.
dna strand
Health Lab
Female genetic markers may have greater effect on hypertension, certain cardiovascular diseases
Female genetic markers may have greater effect on hypertension, certain cardiovascular diseases
Adult performs CPR on a young athlete, illustration with red and blue figures
Health Lab
Sudden cardiac arrest in young athletes: 5 things parents should know
Sudden cardiac arrest in young athletes: 5 things parents should know
Provider takes a pulse oximetry reading from a patient's finger
Health Lab
Inaccurate pulse oximeter readings could limit transplants, heart pumps for Black patients with heart failure
Racially biased readings of oxygen levels in the blood using pulse oximeters may further limit opportunities for Black patients with heart failure to receive potentially lifesaving treatments, such as heart pumps and transplants
Illustration of a magenta heart with white plaque on a golden background.
Health Lab
What is heart disease?
Tanuka Piech, M.D., a cardiologist at the University of Michigan Health Frankel Cardiovascular Center, answers questions about heart disease, why we should care and what we can do to help prevent it.
Woman sweating hot flash fan
Health Lab
Menopause and migraines: New findings point to power of prevention
Women who have both migraines and a long-term history of hot flashes and/or night sweats have a slightly higher risk of heart disease and stroke, and young women who have migraines have a higher risk of later persistent menopause symptoms.