Source: University of Alabama at Birmingham
Summary: In a collaborative study, researchers have found mechanistic links between older stored red blood cell transfusions and subsequent bacterial pneumonia.
Human blood from donors can be stored for use up to 42 days, and it is a mainstay therapy in transfusion medicine. However, recent studies looking back at patient records have shown that transfusion with older, stored blood is associated with adverse effects. For severely injured patients who have massive bleeding and receive many transfusion units, older blood was associated with dysfunction in blood flow, increased injury and inflammation in critical end organs, and lung infection. During storage and upon transfusion, stored red blood cells lyse open, releasing free heme (a component of hemoglobin responsible for binding to oxygen). While in the red blood cell, heme is relatively safe; but once outside the confines of the red cells, free heme is toxic and can cause tissue injury. Researchers from the University of Alabama at Birmingham in a collaborative study using a mouse model have found mechanistic links between older stored red blood cell transfusions and subsequent bacterial pneumonia. This may reveal new approaches to improve the safety of stored red blood cell transfusions. The study findings were published in the journal PLOS Medicine.
In this study, mice were resuscitated after trauma and hemorrhage, using either fresh or two-week-old stored blood. Two days later, they were challenged by instilling the lungs with the bacteria Pseudomonas aeruginosa. A two-week storage of mouse blood approximates storage of human RBCs for 42 days. Compared to fresh blood, resuscitation with the stored blood significantly increased bacterial lung injury, as shown by higher mortality, and increases in fluid accumulation and bacterial numbers in the lungs. A connection between free heme and infection susceptibility and severity was shown two ways. First, Pseudomonas aeruginosa-induced mortality was completely prevented by the addition of hemopexin, a scavenging protein in humans that removes free heme from the blood. Second, adding an inhibitor of a cell surface receptor called toll-like receptor 4, or genetically removing that receptor from mice, also prevented the bacteria-induced mortality.
Finally, in a 16-month study, the researchers found that human trauma-hemorrhage patients who received large amounts of transfused blood were also receiving amounts of free heme sufficient to overwhelm the normal amounts of hemopexin found in a person’s blood.
Patel, Pittet and colleagues said, “Clinically, our findings underscore the need to establish whether the storage age of transfused red blood cells correlates with increasing levels of free heme after transfusion, and whether low ratios of hemopexin to free heme will identify patients at greater risk for adverse outcomes after massive transfusions.”
More Information: Brant M. Wagener et al, “Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study”, PLOS Medicine (2018). DOI: 10.1371/journal.pmed.1002522