Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Lamy, Maurice; Daily, Elaine K.; Brichant, Jean-François; Larbuisson, Robert; Demeyere, Roland; Vandermeersch, Eugéne; Lehot, Jean‐Jacques; Parsloe, M.; Berridge, John C.; Sinclair, Colin; Baron, J. F.; Przybelski, Robert J.

doi:10.1097/00000542-200003000-00007

Cited by 139 publications

(90 citation statements)

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“…This would include situations of severe vascular hemolysis, such as sickle cell disease, paroxysmal nocturnal hemoglobinuria, severe thalassemias, and hereditary spherocytosis, whereby elevated levels of cell-free Hb overwhelm the normal clearance processes, leading to Hb oxidation, vascular injury, and thrombosis, hallmark features of severe hemolytic syndromes (7)(8)(9)(10). Second, the infusion of hemoglobin blood substitutes, whereby chemically modified or genetically engineered Hb molecules are infused at levels that greatly exceed the body's capacity to neutralize free Hb, results in oxidative injury, vascular dysfunction, and thrombotic events in ischemic patients (11)(12)(13). Third, clinical situations associated with the accumulation of RBCs outside the vessel lumen, including intracerebral hemorrhage, RBC extravasation at sites of venous insufficiency, and RBC accumulation in atherosclerotic plaques, lead to increased oxidative stress and tissue injury (14,40).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly administration of purified recombinant hemoglobin to humans promotes vascular injury and arterial thrombosis, precipitating acute myocardial infarction (11)(12)(13). Some of these vascular effects are related to nitric oxide scavenging by excess plasma hemoglobin, whereas others are linked to cytotoxic, proinflammatory, and pro-oxidant effects of iron-containing hemoglobin and heme (14 -19).…”

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confidence: 99%

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Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury

Woollard

Sturgeon

Chin-Dusting

et al. 2009

Journal of Biological Chemistry

106

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The release of redox-active iron and heme into the bloodstream is toxic to the vasculature, contributing to the development of vascular diseases. How iron induces endothelial injury remains ill defined. To investigate this, we developed a novel ex vivo perfusion chamber that enables direct analysis of the effects of FeCl 3 on the vasculature. We demonstrate that FeCl 3 treatment of isolated mouse aorta, perfused with whole blood, was associated with endothelial denudation, collagen exposure, and occlusive thrombus formation. Strikingly exposing vessels to FeCl 3 alone, in the absence of perfused blood, was associated with only minor vascular injury. Whole blood fractionation studies revealed that FeCl 3 -induced vascular injury was red blood cell (erythrocyte)-dependent, requiring erythrocyte hemolysis and hemoglobin oxidation for endothelial denudation. Overall these studies define a unique mechanism of Fe 3؉ -induced vascular injury that has implications for the understanding of FeCl 3 -dependent models of thrombosis and vascular dysfunction associated with severe intravascular hemolysis.Iron and heme-containing moieties are indispensable for the normal transport of oxygen in the blood; however, once released into the bloodstream these molecules are highly toxic to the vasculature because of their pro-oxidative effects on the endothelium (1-3). Humans have therefore evolved sophisticated iron transport and sequestration systems as well as hememetabolizing enzymes to rapidly clear iron and heme from the circulation (4, 5). There is growing evidence that defects in these natural protective mechanisms lead to endothelial dysfunction and vascular disease, and as a consequence, methods that reduce the pro-oxidative effects of iron and heme may have therapeutic benefit (2).Clinical syndromes associated with marked intravascular hemolysis and circulating free hemoglobin, such as sickle cell disease, paroxysmal nocturnal hemoglobinuria, thalassemias, and hereditary spherocytosis, lead to endothelial dysfunction, thrombosis, and vascular disease (5-10). Similarly administration of purified recombinant hemoglobin to humans promotes vascular injury and arterial thrombosis, precipitating acute myocardial infarction (11-13). Some of these vascular effects are related to nitric oxide scavenging by excess plasma hemoglobin, whereas others are linked to cytotoxic, proinflammatory, and pro-oxidant effects of iron-containing hemoglobin and heme (14 -19). Interestingly elevated levels of body iron stores are associated with an increased risk of myocardial infarction, and carriers of the hemochromatosis gene have an increased risk of myocardial infarction and cardiovascular death (20,21). Whether the pro-oxidative effects of iron per se are proatherogenic remains controversial; however, in the context of erythrocyte-dependent release of hemoglobin and heme, redox-active iron is likely to play an important role in promoting vascular dysfunction.The well defined pro-oxidative properties of redox-active iron have been exploited expe...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury

Woollard

Sturgeon

Chin-Dusting

et al. 2009

Journal of Biological Chemistry

106

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“…2 Other investigators have also encountered the same problem. 23 In a recent multicentre study evaluating the efficacy of a Hb solution to reduce allogenic blood transfusions, attending physicians adopted the same attitude and, mean Hb level at discharge was also 100 g·L -1 . Thus, though we now have many strategies to reduce the perioperative administration of allogenic blood transfusions, the battle to eliminate allogenic blood products from the surgical setting is far from over.…”

Section: Conclusion : L'at Ne Réduit Pas Les Pertes Sanguines Mesuréementioning

confidence: 99%

Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement

Lemay

Guay

Côté

et al. 2004

Can J Anesth/J Can Anesth

112

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“…Development of oxidative stress and down-stream events prime the RBC to get lysed. Infusion of hemoglobin solution in healthy volunteers as well as a variety of acquired and iatrogenic hemolytic disorders suggest links between hemolysis and hemoglobenia [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Methemoglobin Mediated Early ROS Spike Triggers Osmotic Fragility and RBC Destruction: An Insight into the Enhanced Hemolysis During Malaria

Balaji

Trivedi

2011

Ind J Clin Biochem

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Malaria infection is known to cause severe hemolysis due to production of abnormal RBCs and enhanced RBC destruction through apoptosis. Infected RBC lysis exposes uninfected RBC to the large amount of pro-oxidant molecules such as methemoglobin. Methemoglobin (MetHb) exposure dose dependently makes RBCs susceptible to osmotic stress and causes hemolysis. MetHb mediated oxidative stress in RBC correlated well with osmotic fragility and hemolysis. Interestingly, a reactive oxygen species (ROS) spike at 15 min was responsible for the observed effects on RBC cells. Two natural antioxidants N-acetyl cysteine and mannitol protected the RBC from MetHb-mediated defects, which clearly indicated involvement of oxidative stress in the process. MetHb due to its pseudo-peroxidase activity produces ROS in the external microenvironment. Therefore, classical peroxidase inhibitors were tested to probe peroxidase activity mediated ROS production with defects in RBCs. Clotrimazole (CLT), which irreversibly inactivates the MetHb (CLTMetHb) and abolishes peroxidase activity, did not produce significant ROS outside RBC and was inefficient to cause osmotic fragility and hemolysis. Hence, initiating a chain reaction, MetHb released from ruptured RBC produces significant ROS in the external microenvironment to make RBC membrane leaky and enhanced hemolysis. Together data presented in the current work explored the role of MetHb in accelerated humorless during malaria which could be responsible for severe outcomes of pathological disorders.

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Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Abstract: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.

Cited by 139 publications

References 0 publications

Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury

Erythrocyte Hemolysis and Hemoglobin Oxidation Promote Ferric Chloride-induced Vascular Injury

Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement

Extracellular Methemoglobin Mediated Early ROS Spike Triggers Osmotic Fragility and RBC Destruction: An Insight into the Enhanced Hemolysis During Malaria

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