Is blood safe for you? Blood transfusions are one of the most common procedures in medicine, but a host of recent studies have suggested many blood transfusions can actually inflict harm, such as heart attack, kidney injury, multi-organ failure and death. Scientists now suggest that modifying banked blood could help it deliver more oxygen and prevent these problems, findings detailed this week in the Proceedings of the National Academy of Sciences.
Red blood cells possess the pigment hemoglobin, which helps deliver oxygen around the body. With this in mind, doctors carry out blood transfusions with the aim of keeping tissues alive, with roughly 85 million units of human blood collected each year.
Although the world’s blood supplies are generally safe from the point of view of disease, blood can undergo a number of biochemical changes while stored. This knowledge led physician scientist Jonathan Stamler at Case Western Reserve University in Cleveland and his colleagues to suspect that stored blood might actually fail to deliver oxygen properly, thus causing damage.
“Contrary to what one might think, giving people blood usually does not make people better and actually runs the risk of making them worse,” Stamler says. “It suggests there’s something wrong with blood. Nowadays people are transfused with blood only if they’ve lost very large amounts of it already — doctors are waiting longer and longer before transfusion.
The molecule that most people think of when it comes to hemoglobin is oxygen, but there are others — for instance, the pigment helps remove carbon dioxide from tissues as well. Another key chemical linked with hemoglobin is nitric oxide, which helps dilate blood vessels and enable oxygen-loaded red blood cells to reach tissues. Nitric oxide is carried in red blood cells in the form of S-nitrosothiol (SNO), which is commonly bound with hemoglobin to form SNO-hemoglobin.
“The two most famous examples of nitric oxide’s uses for dilating blood vessels are nitroglycerin and Viagra,” Stamler says.
Banked red blood cells are stored in a mildly acidic solution that accelerates the decay of SNO-hemoglobin. Indeed, past studies revealed SNO-hemoglobin levels in blood dropped by more than 80 percent within seven days of storage and remains low thereafter. The scientists reasoned that restoring SNO-hemoglobin to banked blood could help prevent ischemia — that is, inadequate blood flow to organs and tissues — during blood transfusions.
“Nobody is really using blood therapeutically right now — the way we give blood today is in the hope of preventing someone from getting worse, and no one gives it to help people get better,” Stamler says. “I think this work might open doors for blood as a new line of therapy — it might even serve as a treatment for heart attacks, for sickle cell anemia, for stroke, for shock.”
Stamler and his colleagues performed a variety of blood transfusion experiments with renitrosylated cells — that is, cells with restored SNO-hemoglobin levels. In mice, administering banked red blood cells decreased oxygen levels in skeletal muscle, but infusing renitrosylated cells kept tissue oxygen levels regular. In rats, hemorrhage-triggered drops in muscle oxygen levels were also corrected with renitrosylated cells. Similar results were seen in sheep that were anemic after a few days of bloodletting, both with anesthetized and awake.
Future clinical trials could see if restoring SNO-hemoglobin to banked blood could indeed help protect millions of patients.
“We’ve developed ways to renitrosylate blood effectively and fairly cheaply,” Stamler adds. He also notes they have patented technologies for renitrosylation.