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PubMed: 30281034

Title
When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?
Journal
Current opinion in hematology
Volume
25
Issue
None
Pages
452-458
Date
2018-11-01
Authors
Buehler PW | Karnaukhova E

Evidence 3d6c6a01c8
JSON

In mice, this response was attenuated after administration of the TLR-4 inhibitor, TAK-242, suggesting hemin potentiates pulmonary macrophage activation and inflammation through hemin-induced TLR-4 receptor binding [27].

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

a(CHEBI:heme) increases bp(MESH:"Macrophage Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 6213063e7e
JSON

The causes for RBC-based toxicant exposures are multifactorial; however, following acute transfusion, the most common occurs during the processes of extravascular hemolysis, which includes macrophage erythrophagocytosis followed by macrophage death [1&&], release of iron, transferrin (Tf) saturation and, finally, accumulation of labile plasma iron (LPI) [2].

a(HM:"Blood Transfusion, Acute") increases bp(MESH:Phagocytosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

bp(MESH:Phagocytosis) increases bp(GO:"macrophage apoptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

bp(MESH:Phagocytosis) increases a(CHEBI:"iron(2+)") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

bp(MESH:Phagocytosis) increases path(HP:"Elevated transferrin saturation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

bp(MESH:Phagocytosis) increases a(HM:"Labile iron", loc(MESH:Plasma)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence 788ebeebf2
JSON

Acute large volume blood transfusion or administration of blood units at later stages of storage causes elevation of bilirubin, Tf saturation and LPI in animals [18&&] and humans [19&&].

a(HM:"Blood Transfusion, Acute") increases a(CHEBI:bilirubin) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

a(HM:"Blood Transfusion, Acute") increases path(HP:"Elevated transferrin saturation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

a(HM:"Blood Transfusion, Acute") increases a(HM:"Labile iron", loc(MESH:Plasma)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence a77bec7ac2
JSON

Conversely, chronic transfusions associated with b-thalassemia major and sickle cell disease lead to hemochromatosis with end organ injury.

a(HM:"Blood Transfusion, Chronic") increases path(MESH:Hemochromatosis) View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence ee126ed706
JSON

Accumulation of iron in tissue parenchyma with subsequent hemochromatosis is a well-known problem in chronic transfusion-dependent diseases such as b-thalassemia major, and in sickle cell disease patients when stroke prevention is indicated.

a(HM:"Blood Transfusion, Chronic") increases path(MESH:Hemochromatosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence f19da2fdb3
JSON

For example, cardiac iron accumu -lation is more common in transfused thalassemia patients, whereas liver iron accumulation is most common in transfused sickle cell disease patients.

a(HM:"Blood Transfusion, Chronic") increases a(MESH:Iron, loc(MESH:Heart)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
beta-Thalassemia
Text Location
Review

a(HM:"Blood Transfusion, Chronic") increases a(MESH:Iron, loc(MESH:Liver)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
Text Location
Review

Evidence 9b2113829e
JSON

For example, Hb and subsequently, hemin accumulate during storage of human blood as RBC membrane integrity decreases [4].

a(HM:"stored erythrocytes") increases bp(MESH:"Erythrocyte Deformability") View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence 83b417508c
JSON

There is a clear need for, and medical benefit from, blood transfusions; nonetheless, administration of red blood cells (RBCs) does result in exposure to toxicants specific to hemoglobin (Hb) and its degradation components, hemin and iron.

a(MESH:"Blood Transfusion") increases p(HGNC:HBB) View Subject | View Object

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Text Location
Review

a(MESH:"Blood Transfusion") increases a(CHEBI:heme) View Subject | View Object

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Text Location
Review

a(MESH:"Blood Transfusion") increases a(CHEBI:"iron(2+)") View Subject | View Object

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Text Location
Review

Evidence 3e54b182e1
JSON

In diseases of intravascular hemolysis, Hp is often not detectable and lower Hp levels are associated with transfusion.

a(MESH:"Blood Transfusion") decreases p(HGNC:HP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 912def7e06
JSON

Because of large exposures to iron that occur in both disorders following transfusion, patients are inevitably prescribed small molecule iron chelation and the concomitant monitoring that is required.

a(MESH:"Iron Chelating Agents") decreases a(CHEBI:"iron(2+)") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence f451609cb9
JSON

Of the biological components known to bind hemin, Hpx is by far the most efficient with a dissociation constant (Kd) lower than 1 x 10–13 M; as a result, after binding, the transfer of hemin from Hpx to other proteins or lipids is not possible [24].

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 86214d09a5
JSON

Once bound to hemin, the Hpx-hemin complex prevents oxidative reactions and facilitates clearance of the complex through macrophage CD91, also referred to as lowdensity lipoprotein receptor-related protein 1.

complex(a(CHEBI:hemin), p(HGNC:HPX)) decreases a(HM:"oxidative reactions") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 0ddc57c7e0
JSON

The pool of di-ferric Tf binds to erythroid cell transferrin receptor 1 (TfR1) and contributes to erythropoiesis [16].

complex(a(MESH:"diferric transferrin"), p(HGNC:TFRC)) increases bp(MESH:Erythropoiesis) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence bf454fcad4
JSON

Hp is a plasma glyco-protein that normally circulates in within a concentration range of 0.3–2mg/ml and is the putative scavenger of cell-free Hb with a high affinity (KD¼10–12M) for Hb dimers (Fig. 1 A,B and Fig. 2 C [31]).

p(HGNC:HP) decreases p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 5762835da1
JSON

Tf is an abundant plasma glycoprotein that normally circulates at a high concentration (2–4mg/ml) to prevent accumulation of LPI.

p(HGNC:TF) decreases a(HM:"Labile iron", loc(MESH:Plasma)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence 256fc7d30a
JSON

Sequestration of LPI and prevention of pro-oxidative effects by the administration of apo-Tf may have clinical relevance following acute and chronic transfusion iron overload.

p(HGNC:TF) decreases a(HM:"Labile iron", loc(MESH:Plasma)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

Evidence 30f704f405
JSON

These studies do begin to suggest that apo-Tf administration could attenuate acute iron overload and hemochromatosis progression following chronic RBC transfusions.

p(HGNC:TF) decreases a(CHEBI:"iron(2+)") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

p(HGNC:TF) decreases path(MESH:Hemochromatosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

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