Increased non‐transferrin bound iron in plasma‐depleted SAG‐M red blood cell units

Marwah, Sukhjinder; Blann, Andrew D.; Harrison, Paul; Lumley, Mark A.; Wright, Josh; McDowell, John M.; Phillips, Jonathan D.; Rea, Carol; Bareford, David

doi:10.1046/j.1423-0410.2002.00153.x

Cited by 18 publications

(15 citation statements)

References 22 publications

(25 reference statements)

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“…Several previous studies have shown that human stored blood also accumulates CFH and NTBI over time, producing levels of CFH from 80 to 90 mM (26) and NTBI from 5 to 15 mM. 33,34 Our study of canine stored blood showed that CFH and NTBI increased over the storage period, reaching mean levels of CFH of 190 mM and of NBTI of 8 mM at 6 weeks. The possibility exists that iron might increase the risk of transfusion by promoting bacterial growth, inducing inflammation, or both, as has been proposed previously.…”

Section: Discussionmentioning

confidence: 51%

“…Our study demonstrates that washing removes 2 sources of iron: 1) iron in the form of NTBI as well as CFH, which accumulates over time in the storage bag, [32][33][34] and 2) older cells that are more likely to hemolyze in vivo after transfusion and release iron. Several previous studies have shown that human stored blood also accumulates CFH and NTBI over time, producing levels of CFH from 80 to 90 mM (26) and NTBI from 5 to 15 mM.…”

Section: Discussionmentioning

confidence: 99%

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Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

Cortés‐Puch

Wang

Sun

et al. 2014

Blood

107

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• Washing older blood before transfusion reduces plasma iron, improving outcomes from established infection in canines.• In contrast, washing fresh blood before transfusion increases in vivo plasma CFH release, worsening outcomes.In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n 5 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7-or 42-dayold washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes. (Blood. 2014;123(9):1403-1411 IntroductionTransfusion of older stored canine universal donor blood in a canine model of experimental Staphylococcus aureus pneumonia results in markedly increased lung injury and mortality rates.1 Transfusion with older blood is also associated with increased levels of cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-TBI (NTBI) and plasma labile iron (PLI). NTBI represents iron excess bound to proteins that do not normally handle circulating iron, and PLI is the toxic iron moiety in plasma. Whereas increased nitric oxide scavenging by CFH causing vasoconstriction and vascular injury and increased available iron promoting bacterial growth represent 2 candidate mechanisms of injury, multiple other biological changes have been documented with increasing blood storage interval.2,3 Some of these changes involve the release into the plasma of biologically active proteins, microvesicles, potassium, acid, and plasticizer, all of which can be reduced by means of standard red cell (RBC) washing procedures. [4][5][6][7][8][9][10] The clinical effect(s) of washing on the RBC storage lesion has not been studied.RBC washing has long been performed to reduce potassium levels in stored blood transfused to neonates, debris from RBCs recovered during surgery, cryoprotectant glycerol from cryopreserved RBCs, and plasma proteins from blood intended for patients who have been sensitized to those proteins.11-13 Automated cell washers cap...

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

Cortés‐Puch

Wang

Sun

et al. 2014

Blood

107

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“…Methaemoglobin levels, which normally constitute < 1% of total haemoglobin in the supernatant [8], are increased by twofold after 3 weeks of storage [56]. Free iron, which is essentially undetectable during the first few days of storage, is ubiquitous in the supernatant after 3 weeks of storage [35,57]. Similar to the post-transfusion effects of microvesicles (outlined above), the contents of the supernatant may also reduce endothelial-derived NO bioavailability and contribute to the oversaturation of the clearance systems for haemolysed red cells in the recipient.…”

Section: Reduced Red Cell Viabilitymentioning

confidence: 99%

The pathophysiology and consequences of red blood cell storage

2014

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Red cell transfusion therapy is a common treatment modality in contemporary medical practice. Although blood collection and administration is safer and more efficient than ever before, red cells undergo multiple metabolic and structural changes during storage that may compromise their functionality and viability following transfusion. The clinical relevance of these changes is a hotly debated topic that continues to be a matter of intense investigation. In the current review, we begin with an in-depth overview of the pathophysiological mechanisms underlying red cell storage, with a focus on altered metabolism, oxidative stress and red cell membrane damage. We proceed to review the current state of evidence on the clinical relevance and consequences of the red cell storage lesion, while discussing the strengths and limitations of clinical studies.

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“…Among the changes, most widely cited changes are [1 & ] a decrease in 2,3-diphosphoglycerate with age with associated increase in oxygen affinity limiting tissue oxygenation [2], an accumulation of potassium and lactic acid [3], an increase in adherence to vascular endothelial cells disrupting flow-perfusion [4], an early loss of nitric oxide bioactivity potentially leading to increased vasoreactivity, and [5] 20]. Finally, transfusion with older blood is not only associated with increased levels of CFH, but also transferrin bound iron (TBI), non-TBI, and plasma labile iron as iron is released from damaged RBCs [21]. Increased iron release has been shown to increase host inflammation and enhance bacterial growth, especially gram-negative species in in-vitro and in-vivo animal studies [ ], and Tung et al [33] demonstrated with lipopolysaccharide (LPS)-treated animals an increase in acute lung injury with older transfused blood that was not seen in animals without LPS-induced inflammation [34].…”

Section: Key Pointsmentioning

confidence: 99%

The influence of the storage lesion(s) on pediatric red cell transfusion

Remy

Natanson

Klein³

2015

Current Opinion in Pediatrics

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Increased non‐transferrin bound iron in plasma‐depleted SAG‐M red blood cell units

Abstract: Increased levels of NTBI become detectable 17-22 days after donation and increase further with storage time. This excess NTBI may promote bacterial infection in iron-loaded individuals.

Cited by 18 publications

References 22 publications

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

The pathophysiology and consequences of red blood cell storage

The influence of the storage lesion(s) on pediatric red cell transfusion

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