New Options for Improving Blood Transfusions

Researchers at Duke University Medical Center (Duke; Durham, NC, USA) conducted a prospective, controlled, mechanistic study to test the hypothesis that RBC storage impairs their ability to release ATP, and that impaired ATP release is injurious in vivo, in part through increasing RBC adhesion. The researchers used human and mouse blood in nude mouse transfusion recipients, performing in vitro and in vivo manipulation of ATP release, supplemental ATP, and antibodies to RBC and endothelial adhesion receptors, to probe the roles of released ATP and adhesion in responses to transfused RBCs.

The researchers found that ATP levels declined markedly within 14 days after blood collection, despite relatively stable levels of ATP within the red blood cells. Inhibiting ATP release promoted the adhesion of stored RBCs to endothelial cells in vitro and RBC sequestration in the lungs of transfused mice in vivo. Unlike transfusion of fresh human RBCs, stored RBC transfusion in mice decreased blood oxygenation and increased extravasation of RBCs into the lung's alveolar air spaces. Similar findings were seen with transfusion of fresh RBCs treated with the ATP release inhibitors glibenclamide and carbenoxolone. These results were prevented by either coinfusion of an ATP analog or pretransfusion incubation of the RBCs with an antibody against the erythrocyte adhesion receptor Landsteiner-Wiener (intercellular adhesion molecule-4). The study was published on July 14, 2011, in the journal Critical Care Medicine.

“We show that the export of ATP is important to prevent red blood cells from sticking to the inner lining of blood vessel walls,” said lead author Timothy McMahon, MD, PhD, an associate professor of medicine at Duke. “With the supply and demand balance for red blood cells very, very tight, it's important to find ways to optimize the benefit of transfusions and extend the shelf life of stored blood.”

ATP is a multifunctional nucleotide used in cells as a coenzyme, often called the "molecular unit of currency" of intracellular energy transfer. It is produced by photophosphorylation and cellular respiration, formed from inorganic phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP), and contains three phosphate groups. ATP transports chemical energy within cells for metabolism and is used by enzymes and structural proteins in many cellular processes, including biosynthetic reactions, motility, and cell division.

Related Links:
Duke University Medical Center