METHODS FOR MANAGING ADVERSE EVENTS IN PATIENT POPULATIONS REQUIRING TRANSFUSION
Method for transfusion medicine to reduce adverse events in transfusion patient populations based on underlying patient physiology.
1 . A method of reducing the risk of an inflammatory response in a human patient in need of a blood transfusion comprising providing oxygen reduced stored blood for transfusion into a human patient in need of a blood transfusion having an increased risk of an inflammatory response, wherein said oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period and a reduced level of at least one inflammatory factor when compared to non-oxygen reduced stored blood stored for an identical storage period.
2 . The method of claim 1 , wherein said human patient in need of a blood transfusion is selected from the group consisting of a surgery patient requiring a tissue perfusion bypass, a patient having chronic vascular inflammation, a patient having chronic inflammatory bowel disease, a patient having chronic obstructive pulmonary disease (COPD), a patient having sickle cell disease, a patient having thalassemia, a patient having organ failure, a patient having systemic inflammatory response syndrome (SIRS), a patient having diabetes mellitus, a patient having Bechet's disease, a patient having rheumatoid arthritis, a patient having smoke inhalation, and a patient having a combination thereof.
3 . The method of claim 2 , wherein said human patient in need of a blood transfusion has a reduction in the risk of a delayed hemolytic transfusion reaction, an injury from ischemia reperfusion, hypercoagulation, a transfusion related acute lung injury (TRALI), systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), or a combination thereof.
4 . The method of claim 2 , wherein said inflammatory response is aggravating an inflammatory response selected from the group consisting of chronic vascular inflammation, chronic inflammatory bowel disease, and combinations thereof.
5 . The method of claim 1 , wherein said at least one inflammatory factor is selected from the group consisting of
leukotriene,
8-isoprostane,
thromboxane,
hydroxyicosatetraenoic acid (HETE), and
combinations thereof.
6 . The method of claim 5 , further comprising an inflammatory cytokine selected from regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin 1, or soluble CD40-ligand (SCD40L).
7 . The method of claim 1 , wherein said storage period is at least 2 days, at least 7 days, at least 14 days, at least 21 days, or at least 28 days.
8 . The method of claim 1 , wherein said human patient in need of a blood transfusion is a patient in need of multiple transfusions.
9 . The method of claim 7 , wherein said storage period is at least two days and oxygen reduced stored blood comprises
a reduced level of thromboxane B2 when said initial oxygen saturation is 5% or less,
an increased level of glutathione (GSH),
a reduced percentage of methemoglobin,
an increased level of ATP, and
an increased level of 2,3-diphosphoglycerate (DPG),
wherein said increase or said reduction in said oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.
10 . The method of claim 9 , wherein said storage period is at least 7 days and said oxygen reduced stored blood further comprises:
an increased ratio of phosphatidylinositol 4-phosphate to phosphatidylinositol (3,4,5)-triphosphate,
wherein said increased ratio in said oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.
11 . The method of claim 10 , wherein said storage period is at least 14 days and said oxygen reduced stored blood further comprises
a reduced level of leukotriene B4,
a reduced level of hydroxyeicosatetraenoic acid (HETE) when said initial oxygen saturation is 10% or less,
an increased level of methylenetetrahydrofolate, and
an increased level of glutamate,
wherein said increase or said reduction in said oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.
12 . The method of claim 11 , wherein said storage period is at least 21 days and said oxygen reduced stored blood further comprises
a higher ratio of GSH to glutathione disulfide (GSSG) (GSH/GSSG ratio) when said 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 said initial oxygen saturation is about 5%,
wherein said increase or said reduction in said oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.
13 . The method of claim 12 , wherein said storage period is at least 28 days and said oxygen reduced stored blood further comprises
an increase level of NADPH,
an increased ratio of NADPH/NADP + , and
an increased level of cysteine,
wherein said increase or said reduction in said oxygen reduced stored blood is relative to non-oxygen reduced stored blood stored for an identical storage period.
14 . (canceled)
15 . (canceled)
16 . A method for reducing oxidative stress in a human patient in need of a blood transfusion comprising providing oxygen reduced stored blood for transfusion into a human patient in need of a blood transfusion having an increased risk for transfusion mediated oxidative stress, wherein said oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period wherein said patient has an increased risk of oxidative stress.
17 . The method of claim 16 , wherein said human patient in need of a blood transfusion is a patient in need of a massive transfusion or chronic transfusions.
18 . A method for reducing the risk of an adverse event in a patient in need of a blood transfusion comprising providing oxygen reduced stored blood for transfusion into a patient in need of a blood transfusion, wherein said oxygen reduced stored blood has an initial oxygen saturation of 20% or less prior to being stored for a storage period, wherein said oxygen reduced stored blood reduces the risk of an adverse even in a patient in need thereof having an increased risk of an adverse event.
19 . The method of claim 18 , wherein said patient in need thereof is a hemoglobinopathy patient.
20 . The method of claim 18 , wherein said 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.
21 . A method for reducing cardiac, renal and gastrointestinal ischemia reperfusion injury in a patient in need of a blood transfusion comprising providing oxygen reduced stored blood that has an initial oxygen saturation of 20% or less prior to being stored for a storage period for transfusion to a human patient in need of a blood transfusion and having an increased risk for cardiac, renal and gastrointestinal ischemia reperfusion injury.
22 . The method of claim 21 , wherein said reduced reperfusion injury is reduced hypercoagulability, cell damage, or oxidative damage.