19 March 2018

Blood stored for longer periods of time may not be suitable for patients suffering massive blood loss and shock, new US research has suggested.

Researchers at the University of Alabama, Birmingham, (UAB) have found mechanistic links between older stored red blood cell transfusions and subsequent bacterial pneumonia, which may lead to new approaches to improve safety of stored red blood cell transfusions.

The research team, made up of scientists from the departments of anaesthesiology and perioperative medicine, biostatistics, emergency medicine, pathology, and surgery, say that haem, a breakdown product from degraded red blood cells, is key.

While it remains in the red blood cell, haem is relatively safe, but free haem is toxic and can cause tissue injury.

Researchers Dr Rakesh Patel, professor of pathology and director of the Center for Free Radical Biology, and Dr Jean-Francois Pittet, professor of anaesthesiology and perioperative medicine at UAB say that finding ways to limit haem exposure or prevent haem toxicity may improve safety of stored red blood cell transfusions.

Their study, which is published in PLOS Medicine, involved resuscitating mice after trauma and haemorrhage, using either fresh or two-week-old stored blood.

Two days later, the lungs were infected with the bacteria Pseudomonas aeruginosa. Compared to fresh blood, resuscitation with the stored blood significantly increased bacterial lung injury and increases in fluid accumulation and bacterial numbers in the lungs.

The researchers say that the connection between free haem and infection susceptibility and severity was evident because infection-induced mortality was prevented by the addition of haemopexin, a scavenging protein in humans that removes free haem from the blood.

The connection was also made because 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.

Transfusion with stored blood induced release of the inflammation mediator HMGB1.

In tissue culture experiments, the researchers found that adding free haem increased permeability in a sheet of endothelial cells, while free haem inhibited macrophages from ingesting Pseudomonas aeruginosa.

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 haemopexin found in a person's blood.

They say: “We recognise that many challenges and questions remain and view our data as hypothesis-generating.

 “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 haemopexin to free haem will identify patients at greater risk for adverse outcomes after massive transfusions.” 

Source: Wagener, B. M., et al. "Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study." PLoS medicine 15.3 (2018): e1002522.

Link: https://doi.org/10.1371/journal.pmed.1002522



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