Methods for Managing Adverse Events in Patient Populations Requiring Transfusion

Abstract

Method for transfusion medicine to reduce adverse events in transfusion patient populations based on underlying patient physiology.

1 - 15 . (canceled) 
     
     
         16 . A method for reducing oxidative stress in a human patient in need of a blood transfusion comprising administering oxygen reduced stored blood for transfusion to the human patient in need of a blood transfusion, wherein the oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period, and wherein the human patient has an increased risk of transfusion mediated oxidative stress. 
     
     
         17 . The method of  claim 16 , wherein the human patient in need of a blood transfusion is a patient in need of a massive transfusion or chronic transfusions. 
     
     
         18 . The method of  claim 16 , wherein the reducing oxidative stress is a reduction of oxidizing compounds, an increase of oxidation protective compounds, or a combination thereof. 
     
     
         19 . The method of  claim 16 , wherein the storage period is two days and the oxygen reduced stored blood comprises
 a reduced level of thromboxane B2 when the blood has an initial oxygen saturation is 5% or less,   an increased reservoir of nicotinamide adenine dinucleotide phosphate (NADP),   an increased reservoir of reduced nicotinamide adenine dinucleotide phosphate (NADPH),   an increased level of glutathione (GSH),   a reduced percentage of methemoglobin,   an increased level of adenosine triphosphate (ATP), and   an increased level of 2,3-diphosphoglycerate (DPG),   wherein the increased level, the increased reservoir, the reduced level, or the reduced percentage in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.   
     
     
         20 . The method of  claim 19 , wherein the storage period is at least 7 days and the oxygen reduced stored blood further comprises
 an increased ratio of phosphatidylinositol 4-phosphate to phosphatidylinositol (3,4,5)-triphosphate,  wherein the increased ratio in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period. 
     
     
         21 . The method of  claim 20 , wherein the storage period is at least 14 days and the oxygen reduced stored blood further comprises
 a reduced level of leukotriene B4,   a reduced level of hydroxyeicosatetraenoic acid (HETE) when the initial oxygen saturation is 10% or less,   an increased level of methylenetetrahydrofolate, and   an increased level of glutamate,  wherein the increased level or the reduced level in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period. 
     
     
         22 . The method of  claim 21 , wherein the storage period is at least 21 days and the oxygen reduced stored blood further comprises
 a higher ratio of GSH to glutathione disulfide (GSSG) when the initial oxygen saturation is between 5% and 10%,   an increased reservoir of nicotinamide adenine dinucleotide (NAD),   an increased reservoir of nicotinamide adenine dinucleotide + hydrogen (NADH), and   a reduced level of dioxidation of Cys152 in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) when the initial oxygen saturation is about 5%, wherein the higher ratio, the increased reservoir, or the reduced level in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period. 
     
     
         23 . The method of  claim 22 , wherein the storage period is at least 28 days and the oxygen reduced stored blood further comprises
 an increased level of NADPH,   an increased ratio of NADPH to nicotinamide adenine dinucleotide phosphate (NADP + ),   an increased level of cysteine, and   an increased level of urate,  wherein the increased level in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period. 
     
     
         24 . The method of  claim 23 , wherein the storage period is at least 42 days and the oxygen reduced stored blood further comprises a reduced level of oxidation of beta-hemoglobin at residue H93, wherein the reduced level in the oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period. 
     
     
         25 . The method of  claim 16 , further comprising transfusing at least one unit of the oxygen reduced stored blood to the human patient. 
     
     
         26 . The method of  claim 16 , wherein the initial oxygen saturation is 10% or less. 
     
     
         27 . The method of  claim 16 , wherein the initial oxygen saturation is 5% or less. 
     
     
         28 . The method of  claim 16 , wherein the initial oxygen saturation is 3% or less. 
     
     
         29 . The method of  claim 16 , wherein the storage period is at least 14 days. 
     
     
         30 . The method of  claim 16 , wherein the human patient in need of a blood transfusion is a sickle cell disease patient with a hemoglobin concentration below 5 grams per deciliter (g/dL), or a thalassemia patient with a hemoglobin concentration below 7 g/dL. 
     
     
         31 . A method for reducing the risk of an adverse event in a human patient in need of a blood transfusion comprising administering oxygen reduced stored blood for transfusion to the human patient in need of a blood transfusion, wherein the oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period, wherein the human patient has an increased risk of an adverse event, and wherein the oxygen reduced stored blood reduces the risk of an adverse event in the human patient. 
     
     
         32 . The method of  claim 31 , wherein the human patient in need of a blood transfusion is a hemoglobinopathy patient. 
     
     
         33 . The method of  claim 31 , wherein the adverse event that is reduced is selected from the group consisting of eryptosis, delayed hemolytic transfusion reaction, defects in red blood asymmetry, severe anemia, reduced frequency of vaso-occlusive crisis, reduced perioperative hypoxia, reduced perioperative hypoperfusion, reduced perioperative acidosis, reticulocytopenia, and combinations thereof. 
     
     
         34 . A method for reducing cardiac, renal and gastrointestinal ischemia reperfusion injury in a human patient in need of a blood transfusion comprising administering oxygen reduced stored blood to the human patient in need of a blood transfusion, wherein the oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period, and wherein the human patient in need of a blood transfusion has an increased risk for cardiac, renal and gastrointestinal ischemia reperfusion injury. 
     
     
         35 . The method of  claim 34 , wherein the reperfusion injury that is reduced is selected from the group consisting of hypercoagulability, cell damage, and oxidative damage.