title: Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells.
abstract: Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.
  
  
  
  To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin.
  
  
  
  Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.
  
  
  
  In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension.
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Jan A
authors: JA
authors: Graw
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Claire
authors: C
authors: Mayeur
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Ivy
authors: I
authors: Rosales
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Yumin
authors: Y
authors: Liu
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Venkata S
authors: VS
authors: Sabbisetti
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Frank E
authors: FE
authors: Riley
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Osher
authors: O
authors: Rechester
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Rajeev
authors: R
authors: Malhotra
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: H Shaw
authors: HS
authors: Warren
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Robert B
authors: RB
authors: Colvin
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Joseph V
authors: JV
authors: Bonventre
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.).
authors: Donald B
authors: DB
authors: Bloch
authors: From Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine (J.A.G., C.M., D.B.B., W.M.Z.), Department of Pathology (I.R., R.B.C.), Department of Pediatrics (F.E.R., O.R., H.S.W.), Cardiovascular Research Center and Cardiology Division, Department of Medicine (R.M.), and Division of Rheumatology, Allergy and Immunology, Department of Medicine (D.B.B.), Massachusetts General Hospital, Harvard Medical School, Boston; and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (Y.L., V.S.S., H.S.W.). wzapol@mgh.harvard.edu.
authors: Warren M
authors: WM
authors: Zapol
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006242:Haptoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D006466:Hemopexin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000378:metabolism; D065227:Transfusion Reaction
chemical_list: D001798:Blood Proteins; C485359:HP protein, human; D006242:Haptoglobins; D006466:Hemopexin
keywords: blood; critical care; haptoglobin; hemoglobin; hemorrhage