Therapeutic says NO more to harmful blood transfusions

Research emerging from the Case Western Reserve University School of Medicine may offer a means to an end for some of blood transfusion’s most harmful aftereffects.

The report released by the medical school outlines a novel approach to restoring nitric oxide (NO) to donated blood in like-animal test subjects. The method — coined renitrosylation therapy by the study team — reinvigorates the bioactive form of NO in blood known as S-nitrosohemoglobin (SNO-Hb), and thus improves tissue blood flow, oxygen delivery and kidney functions in one clean swoop.

“Inasmuch of the world’s supply of banked blood is deficient in SNO-Hb, efforts to restore its levels may hold great therapeutic promise,” said Jonathan Stamler, MD, director of the Institute for Transformative Molecular Medicine and the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation, director of the Harrington Discovery Institute and lead investigator of the study, in a news release.

“One important aspect of our study is the insight that knowledge of banked blood’s SNO-Hb status may be used to judge the efficacy of a transfusion,” he continued.

Access to such information would offer physicians the ability to weed out blood donations that could be potentially harmful and opt for those that would have more restorative power following transfusion.

According to the report: “The loss of NO compromises the ability to dilate blood vessels and thereby deliver oxygen to tissues, which is critical for survival. Red blood cells lacking NO instead would plug small blood vessels and cause heart attacks and kidney failure. In contrast, restoration of NO would ensure oxygen delivery.”

The results aligned with what had been predicted: Whereas tested mice, rats and sheep treated with blood that was not renitrosylated suffered from decreased oxygen levels, those given the NO-enhanced blood showed oxygenation improvement. As such, the therapeutic could make for the reversal of transfusion toxicity and the prevention of heart attack, stroke and kidney damage as well as the better treatment of sickle disease, malaria and other blood disorders.

Moreover, the findings may be reason enough for the Food and Drug Administration to amend current guidelines which peg a successful transfusion as promoting the circulation of 75 percent of banked red blood cells 24 hours after administration.

“Based on our findings, the criteria might need to be revised to include measures of red blood cell function — namely the ability of banked blood to deliver oxygen,” Stamler concluded.

The study crew has obtained a grant from the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health to begin clinical trials to evaluate the method’s effect on banked human blood and a grant that would pave the way for blood transfusion clinical trials has since been applied for.

The study can be found in the latest edition of PNAS: Proceedings of the National Academy of Sciences of the United States of America; it was funded by the NHLBI.