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Why Von Willebrand Factor Could be the Key to Understanding Diseases Like COVID-19

November 01, 2020

Von Willebrand factor, a protein in platelets, helps blood to clot and plays an important role in human health.


Von Willebrand disease (VWD), the most common bleeding disorder, is a genetic condition caused by missing or malfunctioning von Willebrand factor (VWF), a protein in platelets that helps blood to clot. According to the Centers for Disease Control and Prevention, approximately 3.2 million Americans are affected by VWD, 85% of whom are diagnosed with Type 1 VWD. These patients have lower levels of VWF than their healthy peers and often experience serious nosebleeds, easy bruising, heavy menstrual bleeding, and bleeding that lasts longer than normal after an injury or surgery. Oftentimes, patients with VWD require treatment to boost or replace their VWF to minimize the risk of bleeding episodes. 

Early days at Versiti Blood Research Institute

When she first came to Versiti Blood Research Institute (BRI), chemist and Director of Hemostasis Sandra Haberichter, PhD, had a lot to learn. Under the tutelage of Senior Investigator Robert Montgomery, MD, she began studying VWD and worked with Dr. Montgomery to collect samples from patients with VWD to better understand and identify the cell mechanisms that cause the disease.

Together, the two identified a subset of Type 1 von Willebrand disease patients with reduced survival of VWF. They found that these patients make VWF, but instead of it living in the blood for a typical 12-14 hour half-life, it has a reduced half-life of 1-3 hours, which puts patients at risk for serious bleeding. Together, Dr. Haberichter and Dr. Montgomery developed several assays (or tests) through Versiti Diagnostic Labs that have been offered to patients nationwide and help them identify and treat VWD these high-risk patients.

Current von Willebrand disease research

More recently, Dr. Haberichter has focused on understanding why patients with von Willebrand disease clear their von Willebrand factor so quickly. She believes the answer lies in glycosylation, a process that helps determine the structure, function and stability of cell proteins. “Most of these patients have some sort of sequence variation that causes VWD and causes glycosylation to be altered, which would result in clearing VWF,” she said. Dr. Haberichter was just beginning this research when glycobiology expert Karin Hoffmeister, MD, joined the BRI team. Together, they have collected and studied plasma samples from VWD patients to determine if their glycosylation differs from healthy individuals. But there’s a catch.

But because of the VWF’s short half-life, “one of the problems with looking at samples from patients that have reduced VWF survival is that the ‘bad’ VWF has already been cleared from circulation,” Dr. Haberichter said. To combat this phenomenon, Dr. Haberichter and her colleagues are interested in collecting samples from patients treated with a medication called desmopressin, which releases VWF from endothelial cells (the cells that line blood vessels), allowing investigators more time to study the glycosylation process.

Helping in the fight against COVID-19

Compared to other diseases, little is known about COVID-19, but investigators at Versiti Blood Research Institute are hard at work to better understand it. Recently, researchers have found that COVID patients are often at risk for blood clots—and VWF is a key player in initial clot formation. “From what little data is out there, COVID patients have high levels of von Willebrand factor, which may or may not contribute to clotting,” Dr. Haberichter said. “And until you understand the mechanism, you can’t understand the solution.” Dr. Haberichter is working closely with Associate Investigator Shawn Jobe, MD, PhD, medical director at the Comprehensive Center for Bleeding Disorders, to collect samples from COVID patients and study their VWF function, which could potentially lead to better treatments for COVID-19 and subsequent blood clots.

One thing is for sure: Dr. Haberichter feels Versiti Blood Research Institute is perfectly positioned to make an impact in the fight against von Willebrand disease, COVID-19 and many other diseases that affect patients in our communities and around the world. “There are not many other places like the BRI,” she said. “It’s really unique that you have all these experts in one building.” She credits the BRI’s collaborative environment with helping propel innovative research discoveries: “It’s great to have a center of experts working on similar projects with a good opportunity for collaboration.”

About the expert: Sandra Haberichter, PhD, is the director of hemostasis at Versiti Diagnostic Laboratories, Senior Investigator at Versiti Blood Research Institute and an associate professor of pediatrics at the Medical College of Wisconsin.

Versiti Blood Research Institute Articles
Research articles that explore Versiti Blood Research Institute investigators and their expertise in blood health innovation.
Robert Montgomery, MD
Dr. Montgomery is a senior investigator at Versiti Blood Research Institute whose work focuses on understanding bleeding and clotting disorders.
Versiti Blood Research Institute
Versiti Blood Research Institute investigators study blood disorders like hemophilia, blood cancers like leukemia, and other blood diseases.
Sandra L Haberichter, PhD
Dr. Haberichter is a director of hemostasis and senior investigator whose lab is focused on defining the mechanisms that cause Von Willebrand disease (VWD).