Evidence map›Paper›PMID 27515135›Full record

ArticleCirculation2016

Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells.

Jan A Graw, Claire Mayeur, Ivy Rosales, Yumin Liu, Venkata S Sabbisetti, Frank E Riley, Osher Rechester, Rajeev Malhotra, H Shaw Warren, Robert B Colvin and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 74 citations in OpenAlex.

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  12. Non-alcoholic fatty liver disease and liver secretome.Archives of pharmacal research · 2022
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  15. New Insights into Hemopexin-Binding to Hemin and Hemoglobin.International journal of molecular sciences · 2022
    Article
  16. Article
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  18. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Jan A GrawFrom 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.).
Claire MayeurFrom 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.).
Ivy RosalesFrom 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.).
Yumin LiuFrom 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.).
Venkata S SabbisettiFrom 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.).
Frank E RileyFrom 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.).
Osher RechesterFrom 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.).
Rajeev MalhotraFrom 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.).
H Shaw WarrenFrom 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.).
Robert B ColvinFrom 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.).
Joseph V BonventreFrom 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.).
Donald B BlochFrom 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.).
Warren M ZapolFrom 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.
Brigham and Women's Hospital · US

Funding

KIDNEY INJURY MOLECULE-1 IN EPITHELIAL REPAIRR01DK072381 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2005 to 2025
$8.6M
Modulation of Hepcidin-Ferroportin Signaling using Small MoleculesR01DK082971 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BLOCH, DONALD B, PETERSON, RANDALL T · 2009 to 2018
$4.5M
Mouse model for sepsisR01AI059010 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WARREN, H SHAW · 2005 to 2009
$1.9M
The Role of Bone Morphogenetic Proteins in Vascular CalcificationK08HL111210 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MALHOTRA, RAJEEV · 2014 to 2018
$796k
NHLBI NIH HHS K08 HL111210NIAID NIH HHS R01 AI059010NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R01 DK082971
6 · The paper itself

Abstract

backgroundExtracellular 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.

methodsTo 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.

resultsTreatment 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.

conclusionsIn 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.

Indexed as

AnimalsBlood ProteinsErythrocytesHaptoglobinsHemopexinHumansInflammationMiceResuscitationShock, HemorrhagicTransfusion ReactionBlood ProteinsHaptoglobinsHemopexinHP protein, humanbloodcritical carehaptoglobinhemoglobinhemorrhage

Identifiers

PMID27515135
PMCPMC5039096
OpenAlexW2508396194

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.