In healthy people, donut-shaped red cells in the bloodstream carry oxygen and deliver it to all of the body’s tissues. But in people with the inherited condition known as sickle cell disease, red cells stiffen and take on a sickled appearance. Those inflexible cells can stick to each other and to blood vessel walls, causing blockages that interfere with oxygen delivery and lead to sudden crises.
“I’m not sure why nobody’s thought about this before. It makes sense to repurpose this FDA-approved process, but nobody is using it for this.”
— Ian Welsby
To improve blood flow and prevent dangerous complications, many sickle cell patients receive blood transfusions on a monthly basis. But, say Ian Welsby, a cardiac anesthesiologist and intensivist at Duke, and Jay Raval, a pathologist and transfusion medicine expert at UNC, the red blood cells in stored blood become exhausted over time in ways that might limit their lifespan. Now, with funding support from the Clinical and Translational Science Awards (CTSAs) at Duke(link is external) and UNC(link is external), Welsby and Raval are teaming up to explore whether an FDA-approved method for rejuvenating the red blood cells in banked blood might help to extend the time between transfusions for patients with sickle cell disease.
“I’m not sure why nobody’s thought about this before,” Welsby says. “Perhaps we have a unique perspective as an ICU doctor and a blood banker who also manages sickle cell disease. It makes sense to repurpose this FDA-approved process, but nobody is using it for this.”
Pretreating blood prior to transfusion adds an additional layer of complexity, but, he says, “if patients benefit, it’s worth the extra step. Rejuvenated blood may be a better product.”
GIVING BLOOD A BOOST
The FDA-approved product in question is a special solution known as Rejuvesol(link is external). The treatment is used almost exclusively today to extend the life of donated red blood cells representing rare blood types.
“If donated blood is about to expire, we can rejuvenate it and give it a few days of extra life,” says Raval, the blood banking expert. “Or, we can rejuvenate and then freeze it to [effectively] hit the pause button.”
To treat banked blood, experts inject Rejuvesol and then incubate the blood for about an hour. Before healthcare workers can issue the blood for transfusion, they must ensure that the rejuvenation solution is thoroughly washed out of the blood. As Raval explains, Rejuvesol is beneficial to blood cells — essentially feeding the cells to boost their energy levels — but the rejuvenating solution itself isn’t good for the patients later receiving the blood. Fortunately, the washing procedure removes 99.9 percent of the Rejuvesol before transfusion, and the treatment measurably improves the blood in a variety of ways. Despite these benefits, Raval and Welsby say, no one has ever looked to see whether this rejuvenating process might benefit specific groups of patients who must undergo transfusion on a regular basis even when the blood they receive isn’t nearing its expiration date.
There’s reason to suspect people with sickle cell disease might especially stand to benefit from rejuvenated blood. As red cells in donated blood sit on the refrigerator shelf, they tend to change biochemically in ways that make them both stickier and less efficient in oxygen delivery. Since people with sickle cell disease already struggle with these issues, a treatment that could improve the performance of donated red cells in storage might come with health benefits for these patients. It might also extend the interval between treatments, which would decrease the time, cost, and risks associated with transfusions.
To test this idea in the new pilot study, Welsby and Raval will enroll eight sickle cell disease patients in a clinical trial: four at Duke and four at UNC. These patients, who regularly receive monthly blood transfusion sessions, will be alternately given normal and rejuvenated blood. After each session, the researchers will track how long the red cells survive. Instead of 12 trips to the hospital each year — if red cells survive longer — these patients might be able to manage on just 10 trips, the researchers say, noting that the cost of each transfusion session can be over $5,000.
The pretreatment of donated blood might also limit the risk for other complications in sickle cell patients and others in need of regular transfusion. For example, Raval said, people who receive transfusions can develop antibodies against red cells that make it more difficult to find a match. By reducing the frequency of transfusion, rejuvenation treatment might lower that risk.
UNC and Duke both have Comprehensive Sickle Cell Centers that serve and treat many patients with sickle cell disease.
“This is a great example of the opportunity to collaborate between Duke and UNC,” for the benefit of patients, Welsby said. “By drawing on experts at both institutions, we’ve put together a ‘dream team.'” Key collaborators in the project include Dr. Nirmish Shah (Duke, Medicine and Pediatrics), Dr. Tim McMahon (Duke, Medicine) and Dr. Micah Mooberry (UNC, Medicine and Pediatrics).
Welsby and Raval represent one of four teams to receive collaborative grants from the Duke CTSA and the CTSA at UNC-Chapel Hill this year. These Duke/UNC CTSA Collaborative Pilot Program awards are part of an effort to promote inter-institutional collaborations that can turn basic scientific discoveries into advances in patient care.
UNC and Duke are both members of the Clinical and Translational Awards (CTSA) Program, a national consortium created to improve the way biomedical research is conducted across the country. The CTSA program is funded by the National Center for Advancing Translational Sciences (NCATS(link is external)), part of the National Institutes of Health (NIH).