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PubMed: 29603246

Title
Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.
Journal
Transfusion
Volume
58
Issue
None
Pages
1631-1639
Date
2018-07-01
Authors
Cholette JM | Blumberg N | Alfieris GM | Eaton MP | Gensini F | Henrichs KF | Phipps R | Pietropaoli AP | Powers KS | Refaai MA | Rubenstein JS | Spinelli SL | Sweeney D

Evidence afb8f8db66
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There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis.

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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a(CHEBI:"iron(2+)") positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

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a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:"Vascular Diseases") View Subject | View Object

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

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a(CHEBI:heme) positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

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a(CHEBI:heme) positiveCorrelation path(MESH:"Vascular Diseases") View Subject | View Object

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a(CHEBI:heme) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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bp(MESH:"Platelet Activation") positiveCorrelation p(HGNC:HBB) View Subject | View Object

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bp(MESH:"Platelet Activation") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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bp(MESH:"Platelet Activation") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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p(HGNC:HBB) positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

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p(HGNC:HBB) positiveCorrelation path(MESH:"Vascular Diseases") View Subject | View Object

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p(HGNC:HBB) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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path(MESH:"Vascular Diseases") positiveCorrelation p(HGNC:HBB) View Subject | View Object

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path(MESH:"Vascular Diseases") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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path(MESH:"Vascular Diseases") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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

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path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation a(CHEBI:heme) View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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Evidence 8602384869
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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).

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

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Blood
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Anemia, Sickle Cell
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p(HGNC:HP) positiveCorrelation a(CHEBI:lactate) View Subject | View Object

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

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

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Evidence 4cab2c18ab
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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.

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

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p(HGNC:HBB) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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Anemia, Sickle Cell
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p(HGNC:HBB) negativeCorrelation p(HGNC:HP) View Subject | View Object

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

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

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

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

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path(MESH:Thrombosis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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Evidence ffe6f2fcf8
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The postoperative infection rate was significantly higher in children receiving the oldest blood (third tertile, 25-38 days) compared to those receiving the freshest RBCs (first tertile, 7-15 days) (34% vs. 7%; p50.004).

a(HM:"stored erythrocytes") positiveCorrelation path(MESH:Infection) View Subject | View Object

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path(MESH:Infection) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

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Evidence ee4f12121a
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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

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

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

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Evidence c615e55f15
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Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation.

bp(MESH:Immunomodulation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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Anemia, Sickle Cell
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p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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p(HGNC:HBB) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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p(HGNC:HBB) positiveCorrelation bp(MESH:Immunomodulation) View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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Evidence 25955b8868
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Lower haptoglobin levels are associated with poor outcomes, immunomodulation, and unfavorable changes in physiologic measures.12,13,26,27

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

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Evidence b3cf4de2ab
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The median (and mean—data not shown) free Hb levels preoperatively and at all postoperative time points (immediately and 6 and 12 hr postoperatively) were higher (p50.057) in those who later developed a proven thrombosis (Fig. 3 displays the 12-hr data).

p(HGNC:HBB) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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Evidence 4dfe8dc0e5
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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).

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

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

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Evidence 3f8b37a0f6
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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).

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

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

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Evidence 8532c6ebe4
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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).

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

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Evidence f1592f95af
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Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11

path(MESH:"Vascular Diseases") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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path(MESH:Hemolysis) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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path(MESH:Hemolysis) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

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path(MESH:Hemolysis) positiveCorrelation path(MESH:"Vascular Diseases") View Subject | View Object

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path(MESH:Inflammation) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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path(MESH:Thrombosis) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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