Here’s something that might surprise: blood transfusions are the most common medical procedure in the United States, with millions of Americans receiving them each year. They help save lives and that’s in part because the nation’s supplies of donated blood are safer than ever from pathogens such as HIV, hepatitis viruses, and Zika, researchers say.
What’s not so surprising is that existing threats to the blood supply remain, and new ones continue to emerge—which is why a longstanding research program conducted by the NHLBI has been working proactively to minimize the risks and ensure even healthier outcomes for both blood donors and their recipients.
The program, called the Recipient Epidemiology and Donor Evaluation Study, or REDS, is the largest research program of its kind in the United States, and after 30 years, it is about to enter a new, important phase: it will expand its study beyond adults—who have been its exclusive focus—to infants and children.
Originally launched in response to the emerging HIV/AIDS epidemic of the 1980s, REDS already has gone a long way in reducing transfusion-transmitted threats and making donated blood more available, said W. Keith Hoots, M.D., director of the Division of Blood Diseases and Resources at the NHLBI, which has funded the REDS program for the past three decades. “Our mission is to make blood donations as safe as possible,” he noted. “We can greatly reduce risks and we must remain ever vigilant.”
That, he said, means making sure the youngest of the young are protected—and this fourth phase of the study hopes to do just that. Called REDS-IV-Pediatrics (REDS-IV-P), it is a seven-year, multicenter program, which began April 1, 2019 and continues until March 2026. While it will continue conducting epidemiologic and laboratory studies in blood donors and transfusion recipients, researchers said the shift in focus is much-needed.
"For years, we’ve adopted transfusion strategies that were evaluated in adults to babies and children without much attention to the fact that they are physiologically different than adults and may have different transfusion needs,” said Simone Glynn M.D., M.Sc., M.P.H., chief of the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI and project officer for REDS-IV-P.
“The time is right to address critical needs in transfusion safety among infants and children, who as a group are understudied in transfusion research—but highly vulnerable to adverse outcomes,” Glynn noted. “A better understanding of how transfusions affect the neonatal and pediatric populations can lead to improved outcomes and save lives.”
Critically ill pre-term babies need frequent blood transfusions and are among the most heavily transfused pediatric groups. One major reason for blood loss in this population is iatrogenic anemia, or the loss of red blood cells due to frequent blood sampling or testing. But the frequent transfusions that keep them alive carry health risks, including allergic reactions, and studying those responses can help improve safety, Glynn noted.
Unlike for adult transfusion patients, little epidemiologic data on pediatric transfusions currently exists. That means the incidence of adverse transfusion outcomes among infants and children—and the long-term effects of those transfusions—are largely unknown. REDS-IV-P will help fill this existing knowledge gap, Glynn said.
But the research will go far beyond that. As with previous phases of the REDS program, REDS-IV-P will continue to focus on improving the safety and effectiveness of transfusion practices among people with sickle cell disease, the most prevalent genetic blood disorder worldwide. That group is also among the most widely transfused, and to learn more about the impact, the program will study a well-characterized group of about 2,800 people with sickle cell disease in Brazil.
Brazil is a perfect partner for the REDS-IV-P sickle cell program, said Iman Martin, Ph.D., M.Sc., M.P.H., a program director in the NHLBI Blood Epidemiology and Clinical Therapeutics branch who oversees the Brazil component of the REDS-IV-P program. The wide genetic diversity of the country’s sickle cell population and the centralized structure of its health care system provides an optimal research setting for studying transfusion-related outcomes, she noted.
The partnership “allows researchers to study sickle cell transfusion practices faster and more efficiently than researchers could do in a larger, more geographically dispersed sickle cell population elsewhere in the world,” Martin said. “On the other hand, it allows Brazil to have access to cutting-edge technology and other resources that help improve transfusion practices in that country.”
The Brazil component of REDS-IV-P will also continue to monitor emerging infectious threats, such as the Zika, Dengue, and Chikungunya viruses, all of which can pose a danger to the U.S. blood supply. Because mosquito-borne pathogens are widespread in Brazil, the country has helped NHLBI identify new pathogens much more quickly than it could by studying the U.S. blood supply in isolation, Martin noted.
“Partnering with Brazil gives us a head start in finding ways to detect and mitigate these threats, not only in the U.S. but worldwide,” Martin said. “REDS-IV-P allows us to work collaboratively with researchers there to come up with solutions, such as better blood screening techniques, to prevent the spread of emerging threats.”
NHLBI’s Hoots agreed that new technology is critical to ensuring the safety of the blood supply. State-of-the art tests can directly detect the DNA and RNA of pathogens, for example, and also help researchers quickly and accurately spot viral threats in a way that they could not have done just a decade ago.
“While it once took years to identify an unknown pathogen in the blood supply, new technologies are now able to detect pathogens within weeks or even less,” Hoots said.
NHLBI is not alone in this intensive, ongoing effort to safeguard the blood supply. Other federal agencies, including the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration, play key roles. So do state and local health departments, hospitals, blood banks, industry, and associations, such as the American Red Cross, America’s Blood Centers, and AABB (formerly known as the American Association of Blood Banks).
But researchers working with REDS-IV-P said this added level of research makes for an especially thorough study. From infants to people with sickle cell disease— “we’ve got them covered,” Glynn said.
Still, she said, research is just part of the transfusion equation. “Blood donation also plays a crucial part, so please consider being a blood donor,” she added. “It can save lives.”