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p(HGNC:HP)

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Entity

Name
HP
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 1

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 23

a(MESH:"haptoglobin-hemoglobin complex") decreases p(HGNC:HP) View Subject | View Object

Formation of large amounts of haptoglobin– haemoglobin complexes rapidly depletes haptoglobin. PubMed:25307023

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Annotations
Cell Ontology (CL)
macrophage
Text Location
Review

a(CHEBI:heme) positiveCorrelation p(HGNC:HP) View Subject | View Object

First, addition of exogenous Hp both markedly inhibits heme loss and second, as a result of this inhibition, globin precipitation is prevented. PubMed:24486321

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Text Location
Discussion

a(CHEBI:lactate) positiveCorrelation p(HGNC:HP) View Subject | View Object

Preoperative adult normal haptoglobin levels, compared with lower preoperative haptoglobin levels, were associated with significantly lower Day 1 peak blood lactate levels and higher nadir mean arterial pressures on day one (Figs. S1 and S2, available as supporting information in the online version of this paper) as well as on the first and second days postoperatively (data not shown). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Results

a(CHEBI:methemoglobin) negativeCorrelation p(HGNC:HP) View Subject | View Object

No high-spin ferric Hb was present in the control tissues or renal tissues of old blood-transfused, Hp-treated guinea pigs. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

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

In diseases of intravascular hemolysis, Hp is often not detectable and lower Hp levels are associated with transfusion. PubMed:30281034

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

a(MESH:"Fetal Hemoglobin") negativeCorrelation p(HGNC:HP) View Subject | View Object

A negative correlation was found, i.e. an increased plasma cell-free HbF concentration was associated with a decreased plasma Hp concentration, when including all individuals, controls and women with PE (r = -0.335, p-value<0.0001, n = 145)(Fig 1A). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

complex(p(HGNC:HP), p(INTERPRO:"NEAT domain")) hasComponent p(HGNC:HP) View Subject | View Object

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a(MESH:"haptoglobin-hemoglobin complex") positiveCorrelation p(HGNC:HP) View Subject | View Object

Haptoglobin (Hp) is perhaps the most well investigated Hb-clearing molecule. It binds cell-free Hb in plasma [20,21] and the resulting Hp-Hb complex is cleared from blood via binding to the macrophage receptor CD163 [22]. PubMed:26368565

Appears in Networks:
Annotations
MeSH
Placenta
Text Location
Introduction

a(MESH:Morbidity) negativeCorrelation p(HGNC:HP) View Subject | View Object

Increased circulating cell-free Hb, heme, and iron and decreased haptoglobin concentrations have been associated with morbidity and mortality in both animal models and patients.4,5 PubMed:29603246

Appears in Networks:
Annotations
Text Location
Introduction

a(MESH:Mortality) negativeCorrelation p(HGNC:HP) View Subject | View Object

Increased circulating cell-free Hb, heme, and iron and decreased haptoglobin concentrations have been associated with morbidity and mortality in both animal models and patients.4,5 PubMed:29603246

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Annotations
Text Location
Introduction

bp(MESH:Immunomodulation) negativeCorrelation p(HGNC:HP) View Subject | View Object

Lower haptoglobin levels are associated with poor outcomes, immunomodulation, and unfavorable changes in physiologic measures.12,13,26,27 PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

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

However, patients who died had significantly higher plasma cell-free Hb and lower haptoglobin concentrations at all time points, preoperatively and immediately postoperatively and 6 and 12 hours postoperatively (Fig. 1 shows the 12-hr postoperative data). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

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

Children undergoing open heart surgery experience a progressively increasing risk of postoperative infection and thrombosis, increasing need for mechanical ventilation and inotropes, increasing Day 1 through Day 2 peak blood lactate, and decreased nadir mean arterial pressure as the levels of free Hb increase and the levels of haptoglobin decrease. PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

path(HP:"Elevated mean arterial pressure") negativeCorrelation p(HGNC:HP) View Subject | View Object

Preoperative adult normal haptoglobin levels, compared with lower preoperative haptoglobin levels, were associated with significantly lower Day 1 peak blood lactate levels and higher nadir mean arterial pressures on day one (Figs. S1 and S2, available as supporting information in the online version of this paper) as well as on the first and second days postoperatively (data not shown). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Results

path(HP:"Paroxysmal nocturnal hemoglobinuria") decreases p(HGNC:HP) View Subject | View Object

Thus, in severe haemolytic diseases, such as paroxysmal nocturnal haemoglobinuria (PNH) and sickle cell disease (SCD), serum haptoglobin is typically undetectable and plasma haemoglobin is elevated (Tabbara, 1992). PubMed:25307023

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

path(MESH:"Anemia, Sickle Cell") decreases p(HGNC:HP) View Subject | View Object

Thus, in severe haemolytic diseases, such as paroxysmal nocturnal haemoglobinuria (PNH) and sickle cell disease (SCD), serum haptoglobin is typically undetectable and plasma haemoglobin is elevated (Tabbara, 1992). PubMed:25307023

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

path(MESH:"Pre-Eclampsia") negativeCorrelation p(HGNC:HP) View Subject | View Object

Analysis of the Hp concentration in plasma showed a statistically significant decrease in Hp concentration in plasma samples of women with PE as compared to controls (pvalue< 0.0001). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Tricuspid Valve Insufficiency") negativeCorrelation p(HGNC:HP) View Subject | View Object

The median values and associated interquartile ranges for hmox-1 and haptoglobin show that patients with PE+TR+ had lower expression of these genes compared with patients who were PE+TR− or PE− PubMed:26337933

Appears in Networks:
Annotations
MeSH
Pulmonary Embolism
Text Location
Results

path(MESH:Hemolysis) negativeCorrelation p(HGNC:HP) View Subject | View Object

However, in patients with hemolysis Hp depletes early in the course of the disease while levels of Hx remain within the physiologic range for prolonged periods of sustained hemolytic disease [12]. PubMed:26475040

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Abstract

path(MESH:Hemolysis) negativeCorrelation p(HGNC:HP) View Subject | View Object

In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449

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Text Location
Review

path(MESH:Hemolysis) negativeCorrelation p(HGNC:HP) View Subject | View Object

Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

path(MESH:Infection) negativeCorrelation p(HGNC:HP) View Subject | View Object

Adult normal levels of preoperative haptoglobin were associated with a substantially, but not significantly lower rate of infection than lower levels (Table 1, second row). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

path(MESH:Thrombosis) negativeCorrelation p(HGNC:HP) View Subject | View Object

Adult normal levels of preoperative haptoglobin were associated with a substantially and significantly lower incidence of thrombosis than lower levels of haptoglobin (Table 1; row 3). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

Out-Edges 37

p(HGNC:HP) decreases a(HM:"oxidative modification of atheroma lipid") View Subject | View Object

Hemoglobinmediated oxidative modification of lipid extracted from atheromatous lesions was inhibited by haptoglobin (Fig 4A). PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Plaque, Atherosclerotic
Text Location
Results

p(HGNC:HP) decreases a(HM:"oxidative modification of atheroma lipid") View Subject | View Object

Both the hemoglobin-binding protein, haptoglobin,27 and the heme-binding protein, hemopexin, inhibited such oxidative modification of lipids indicating the importance of heme loss and scission in hemoglobin-provoked oxidation of lipids derived from atheromatous lesions. PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
Text Location
Discussion

p(HGNC:HP) decreases bp(MESH:"Lipid Peroxidation") View Subject | View Object

Inhibition of lipid oxidation by either haptoglobin or hemopexin reduced the cytotoxicity (Fig 4B) and HO-1 induction caused by sublethal amounts of pretreated atheromatous lesion lipids (Fig 4C and D). PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Plaque, Atherosclerotic
Text Location
Results

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

Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation following hemolysis. PubMed:24486321

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Text Location
Abstract

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

Haptoglobin (Hp) is a Hb-scavenging plasma glycoprotein which binds non-covalently to hemoglobin dimers that are generated by dissociation of acellular Hb tetramers after hemolysis [6]. PubMed:24486321

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Text Location
Introduction

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

Hp is the first-line scavenger that binds and accelerates the clearance of Hb in the circulation, although the macrophage CD163 receptor has also been the focus of several recent investigations [66– 68]. PubMed:24486321

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Text Location
Discussion

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

Based on clinical observations the Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hx) have been characterized as a sequential defense system with Hp as the primary protector and Hx as a backup when all Hp is depleted during more severe intravascular hemolysis. PubMed:26475040

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Abstract

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

Free Hb is bound by the plasma protein haptoglobin, and the large molecular size Hb: Hp complexes are ultimately cleared by spleen and liver macrophages expressing the Hb scavenger receptor CD163.8 PubMed:26794659

Appears in Networks:
Annotations
MeSH
Liver
Text Location
Introduction

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

Hp treatment prevented renal Hb exposure. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney Tubules
Text Location
Results

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

The prevention of renal Hb filtration by Hp may be a therapeutic strategy to block renal Hb exposure and to rescue renal function in patients with severe hemoglobinuria. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
MeSH
Hemoglobinuria
Text Location
Discussion

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

Thus, the interactions of hemoglobin with haptoglobin, and of heme with hemopexin, ensure safe disposal of potentially dangerous molecules [6,7,15–19] PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

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

However, patients who died had significantly higher plasma cell-free Hb and lower haptoglobin concentrations at all time points, preoperatively and immediately postoperatively and 6 and 12 hours postoperatively (Fig. 1 shows the 12-hr postoperative data). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

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

Children undergoing open heart surgery experience a progressively increasing risk of postoperative infection and thrombosis, increasing need for mechanical ventilation and inotropes, increasing Day 1 through Day 2 peak blood lactate, and decreased nadir mean arterial pressure as the levels of free Hb increase and the levels of haptoglobin decrease. PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

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

free hemoglobin is rapidly cleared from the circulation by several scavenging mechanisms; however, we found that the plasma-free hemoglobin was high and haptoglobin levels were low in the patients examined (Table 1). PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

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

Normally, cellfree hemoglobin will dimerize and rapidly be bound by its hemoglobin scavengers haptoglobin and hemopexin [12]. PubMed:29956069

Appears in Networks:
Annotations
MeSH
Arteries
MeSH
Sepsis
Text Location
Review

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

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]). PubMed:30281034

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

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

On the extracellular level, within the circulation, haptoglobin (Hp) and hemopexin (Hpx) are two of the most prominent scavenger proteins, with antioxidative properties through their capacity to remove cell-free Hb (by Hp) and heme (by Hpx). PubMed:30505280

Appears in Networks:
Annotations
MeSH
Knee
MeSH
Osteoarthritis, Knee
Text Location
Introduction

p(HGNC:HP) decreases a(HM:"oxidative reactions") View Subject | View Object

Probably the most important Hp-mediated abrogation of Hb toxicity is stabilization of heme within the central cavity of the Hb subunits, which almost completely prevents its dissociation and subsequent free heme-mediated oxidative reactions and inflammatory responses. PubMed:24486321

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Annotations
Text Location
Discussion

p(HGNC:HP) decreases path(MESH:Inflammation) View Subject | View Object

Probably the most important Hp-mediated abrogation of Hb toxicity is stabilization of heme within the central cavity of the Hb subunits, which almost completely prevents its dissociation and subsequent free heme-mediated oxidative reactions and inflammatory responses. PubMed:24486321

Appears in Networks:
Annotations
Text Location
Discussion

p(HGNC:HP) positiveCorrelation a(CHEBI:heme) View Subject | View Object

First, addition of exogenous Hp both markedly inhibits heme loss and second, as a result of this inhibition, globin precipitation is prevented. PubMed:24486321

Appears in Networks:
Annotations
Text Location
Discussion

p(HGNC:HP) negativeCorrelation path(MESH:"Tricuspid Valve Insufficiency") View Subject | View Object

The median values and associated interquartile ranges for hmox-1 and haptoglobin show that patients with PE+TR+ had lower expression of these genes compared with patients who were PE+TR− or PE− PubMed:26337933

Appears in Networks:
Annotations
MeSH
Pulmonary Embolism
Text Location
Results

p(HGNC:HP) positiveCorrelation a(MESH:"haptoglobin-hemoglobin complex") View Subject | View Object

Haptoglobin (Hp) is perhaps the most well investigated Hb-clearing molecule. It binds cell-free Hb in plasma [20,21] and the resulting Hp-Hb complex is cleared from blood via binding to the macrophage receptor CD163 [22]. PubMed:26368565

Appears in Networks:
Annotations
MeSH
Placenta
Text Location
Introduction

p(HGNC:HP) negativeCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Analysis of the Hp concentration in plasma showed a statistically significant decrease in Hp concentration in plasma samples of women with PE as compared to controls (pvalue< 0.0001). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

p(HGNC:HP) negativeCorrelation a(MESH:"Fetal Hemoglobin") View Subject | View Object

A negative correlation was found, i.e. an increased plasma cell-free HbF concentration was associated with a decreased plasma Hp concentration, when including all individuals, controls and women with PE (r = -0.335, p-value<0.0001, n = 145)(Fig 1A). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

p(HGNC:HP) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

However, in patients with hemolysis Hp depletes early in the course of the disease while levels of Hx remain within the physiologic range for prolonged periods of sustained hemolytic disease [12]. PubMed:26475040

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HP) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HP) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

p(HGNC:HP) negativeCorrelation a(CHEBI:methemoglobin) View Subject | View Object

No high-spin ferric Hb was present in the control tissues or renal tissues of old blood-transfused, Hp-treated guinea pigs. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

p(HGNC:HP) decreases a(CHEBI:"4-hydroxynon-2-enal") View Subject | View Object

In control, new blood-transfused, and old bloodtransfused, Hp-treated animals, 4-HNE was not detected. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

p(HGNC:HP) causesNoChange act(a(CHEBI:Peroxidase)) View Subject | View Object

However, no changes in peroxidase activity were observed after incubation with haptoglobin or hemopexin (Fig. 2). PubMed:28088643

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) negativeCorrelation a(MESH:Morbidity) View Subject | View Object

Increased circulating cell-free Hb, heme, and iron and decreased haptoglobin concentrations have been associated with morbidity and mortality in both animal models and patients.4,5 PubMed:29603246

Appears in Networks:
Annotations
Text Location
Introduction

p(HGNC:HP) negativeCorrelation a(MESH:Mortality) View Subject | View Object

Increased circulating cell-free Hb, heme, and iron and decreased haptoglobin concentrations have been associated with morbidity and mortality in both animal models and patients.4,5 PubMed:29603246

Appears in Networks:
Annotations
Text Location
Introduction

p(HGNC:HP) negativeCorrelation path(MESH:Infection) View Subject | View Object

Adult normal levels of preoperative haptoglobin were associated with a substantially, but not significantly lower rate of infection than lower levels (Table 1, second row). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) negativeCorrelation path(MESH:Thrombosis) View Subject | View Object

Adult normal levels of preoperative haptoglobin were associated with a substantially and significantly lower incidence of thrombosis than lower levels of haptoglobin (Table 1; row 3). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) positiveCorrelation a(CHEBI:lactate) View Subject | View Object

Preoperative adult normal haptoglobin levels, compared with lower preoperative haptoglobin levels, were associated with significantly lower Day 1 peak blood lactate levels and higher nadir mean arterial pressures on day one (Figs. S1 and S2, available as supporting information in the online version of this paper) as well as on the first and second days postoperatively (data not shown). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) negativeCorrelation path(HP:"Elevated mean arterial pressure") View Subject | View Object

Preoperative adult normal haptoglobin levels, compared with lower preoperative haptoglobin levels, were associated with significantly lower Day 1 peak blood lactate levels and higher nadir mean arterial pressures on day one (Figs. S1 and S2, available as supporting information in the online version of this paper) as well as on the first and second days postoperatively (data not shown). PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) negativeCorrelation bp(MESH:Immunomodulation) View Subject | View Object

Lower haptoglobin levels are associated with poor outcomes, immunomodulation, and unfavorable changes in physiologic measures.12,13,26,27 PubMed:29603246

Appears in Networks:
Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

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