A mechanism related to adverse effects of free haem may explain why stored blood increases mortality from pneumonia compared to fresh blood when used in large volume resuscitation, US research suggests.

Working with animal models, researchers at the University of Alabama at Birmingham found that stored blood had resulted in worse outcomes compared to fresh blood via pathways related to free haem, which could be overcome by hemopexin and toll-like receptor 4 (TLR4)  inhibition.

The findings, published in PLOS Medicine suggest that methods that limit haem exposure or prevent haem toxicity would help to improve safety of stored red blood cell transfusions.

In the study, mice were resuscitated after trauma and haemorrhage, using either fresh or two-week-old stored blood (equivalent to storage of human red blood cells for 42 days). Two days later, they were challenged by instilling the lungs with the bacteria Pseudomonas aeruginosa.

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.

In vitro experiments showed that human trauma-haemorrhage patients who received large amounts of transfused blood were also receiving amounts of free haem, sufficient to overwhelm the normal amounts of hemopexin found in a person’s blood.

And in animal models, the researchers showed that P. aeruginosa-induced mortality was completely prevented by the addition of hemopexin, which removes free haem from the blood.

They also showed that bacterial-induced mortality could be prevented by adding an inhibitor of toll-like receptor 4 (TLR4), which is known to activate free haem to cause toxicity.

The  researchers acknowledged that the data was hypothesis-generating, but said their study provided clear clues that free haem was a key player in adverse effects associated with stored RBC transfusion after trauma haemorrhage.

“Clinically, our findings underscore the need to establish whether the storage age of transfused red blood cells correlates with increasing levels of free haem after transfusion, and whether low ratios of hemopexin to free haem will identify patients at greater risk for adverse outcomes after massive transfusions.”