The Predictive Value of Serum Haptoglobin in Hemolytic Disease

Marchand, Anthony; Galen, Robert S.; Lente, Frederick Van

doi:10.1001/jama.1980.03300450023014

Cited by 90 publications

(34 citation statements)

References 6 publications

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“…4 Systemic HPT concentrations are used clinically as a marker of hemolysis. 5 Decreased, often undetectable, HPT concentrations are found in patients with both intravascular as well as extravascular hemolysis. 6 Normal HPT concentrations in adults are higher than those in children.…”

Section: Introductionmentioning

confidence: 99%

‘Haptoglobin concentrations in preterm and term newborns’

et al. 2011

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Objective: To measure systemic haptoglobin (HPT) concentrations from birth in preterm (PT) and T newborns. To compare HPT in newborns without hemolysis or infection with values in bacteremic newborns.Study Design: HPT was measured using enzyme-linked immunosorbent assay in 30 PT and 28 T newborns without hemolysis or infection at birth (cord blood), on days of life 2 to 4, and at 1 to 2 weeks of life. Concentrations were measured in eight additional newborns with bacteremia. Wilcoxon-Mann-Whitney test was used for comparisons.Result: HPT concentrations were consistently measurable from birth in PT and T neonates. Values were significantly greater in 2-to 4-day-old PT and T newborns than in newborns at birth (P<0.01). Bacteremic newborns had higher HPT concentrations than newborns without infection (P ¼ 0.033). Conclusion:HPT is detectable from birth in PT and T newborns. HPT concentrations increase in bacteremic newborns. HPT levels may have clinical utility in the evaluation of neonatal sepsis.

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Section: Introductionmentioning

confidence: 99%

‘Haptoglobin concentrations in preterm and term newborns’

et al. 2011

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“…16 Removal of prooxidant and pro-inflammatory Hb may, in fact, be an important function of macrophages during intravascular hemolysis and on the local release of large quantities of free Hb at sites of injury. However, the rapid decline that occurs in Hp binding capacity during hemolytic anemia, [18][19][20] malaria, 21,22 and local extravascular Hb release suggests the existence of a highly efficient, but Hp-independent, Hb clearance pathway. Neither Hp knockout mice 23,24 nor humans with anhaptoglobinemia 25 display compromised plasma Hb clearance, and the cellular distribution of Hb uptake in liver and spleen is not changed during hemolysis in haptoglobin deficiency, 26 providing additional evidence of such a pathway.…”

Section: Introductionmentioning

confidence: 99%

CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin

Schaer

Buehler

et al. 2006

Blood

250

177

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CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages. Because Hp binding capacity is exhausted during severe hemolysis, an Hp-independent Hb-clearance pathway is presumed to exist. We demonstrate that Hb interacts efficiently with CD163 in the absence of Hp. Not only is Hb internalized into an endosomal compartment by CD163 as a result of active receptordependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor-binding site. Free Hb further induces heme oxygenase mRNA expression in CD163 ؉ HEK293 cells, but not in CD163 ؊ cells. Additional evidence for Hp-independent Hb-CD163 interaction is provided by the demonstration that CD163 mediates the uptake of ␣␣-DBBF crosslinked Hb, a chemically modified Hb that forms minimal Hp complexes. Moreover, certain modifications to Hb, such as polymerization or the attachment of specific functional groups (3 lysyl residues) to the ␤-Cys93 can reduce or enhance this pathway of uptake. In human macrophages, Hp-complex formation critically enhances Hb uptake at low (1 g/mL), but not at high (greater than 100 g/mL), ligand concentrations, lending support for a concentrationdependent biphasic model of macrophage Hb-clearance. These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion. IntroductionHeme, which is mainly derived from hemoglobin (Hb), is a strong oxidant and has potent pro-inflammatory properties. These properties become apparent if the intricate intra-erythrocytic compartmentalization of heme is compromised after the destruction of erythrocytes. [1][2][3][4] Large quantities of free hemoglobin can be found in the circulation of patients who have undergone transfusion with cell-free hemoglobin products as a blood substitute. 5 Macrophages are the primary scavengers of Hb after systemic hemolysis and during wound healing. These cells also play a key role in the clearance of exogenously administered blood substitutes. 6 CD163 is a member of the cysteine-rich scavenger receptor family and is exclusively expressed by cells of monocyte/ macrophage lineage. 7 Resident tissue macrophages contain the highest levels of CD163, most notably Kupffer cells in the liver and macrophages within the bone marrow and spleen red pulp. [8][9][10] To date, the Hb-haptoglobin (Hp) complex is the only known ligand of CD163, 11,12 and neither Hp alone nor free Hb has been found to display high-affinity binding to the receptor. Because the Hb-Hp complex binds to CD163 with high affinity and the receptor system has a high endocytotic capacity, CD163 is thought to mediate the clearance of Hb-Hp complexes from the blood. 13 Several lines of evidence indicate that CD163 plays a key role in the anti-inflammatory and wound-healing process. First, there is a high level of CD163 expression by macrophages during the down-regulatory phase of inflammatory reactions. 8,14 Second, CD163 expression is strongly induced by glucocorticoids 15,16 and...

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“…However, in comparatively mild forms of a haemolytic process, the reticulocyte count lacks conclusiveness and any diagnosis derived from it is doubtful (DRecently, Marchand et al (2) supported the routine use of the serum haptoglobin determination in the diagnosis of haemolytic diseases.…”

Section: Introductionmentioning

confidence: 99%

Haptoglobin Typing, is It Clinically Necessary for a Reliable Determination of Haptoglobin with the Single Radial Immunodiffusion Technique?

Rijn¹,

Kruit²,

Schrijver³

1984

Clinical Chemistry and Laboratory Medicine

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Summary: Over a period of three years we determined haptoglobin levels by single radial immunodiffusion (RID) and the haptoglobin phenotype in over 1700 samples of patients suspected of a haemolytic disease.As haptoglobin phenotyping is rather laborious and therefore an expensive method, we re-evaluated the diagnostic need for phenotyping.From our reference values for the respective phenotypes of haptoglobin it may be theoretically argued that phenotyping is still desirable when the RID value is in the ränge 400-1170 mg/1. Limiting ourselves to suspected haemolytic diseases, one can abolish phenotyping beyond this narrow ränge without withdrawing important clinical Information. From the total group it appeared that 480 samples lay in this ränge. In 72 samples (15% of 480) the evaluation of the RID values was essentially altered by phenotyping. Careful examination of the medical records indicated that in a number of cases laborious phenotyping had indeed contributed to the diagnosis. Ist die Haptoglobin-Typisierung klinisch erforderlich für eine zuverlässige Bestimmung von Haptoglobin mit der einfachen radialen Immunodiffusion?Zusammenfassung: Wir bestimmten in über 1700 Proben von Patienten mit Verdacht auf eine hämolytische Erkrankung während drei Jahren die Häptoglöbinkonzentration mit der einfachen radialen Immundiffusion und zugleich den Haptoglobin^Phänotyp.Wir prüften erneut die diagnostische Notwendigkeit der Phänotypisierung, da diese arbeitsaufwendig und deshalb teuer ist.Aus unseren Referenzwerten für die entsprechenden Phänotypen von Haptoglobin kann theoretisch abgeleitet werden, daß Phänotypisierurig noch wünschenswert ist, sofern die mit radialer Immundiffusion bestimmte Konzentration im Bereich von 400-1170 mg/1 liegt. Bei Beschränkung auf Verdachtsfälle hämolytischer Erkrankungen kann die Phänotypisierung oberhalb dieses schmalen Bereichs ohne Verlust wesentlicher klinischer Information unterlassen werden. In diesem Bereich lagen 480 Proben der gesamten Gruppe. Bei 72 (15% von 480) Proben änderte sich aufgrund der Phänotypisierung die Beurteilung der Ergebnisse der radialen Immundiffusion. Eine sorgfältige Durchsicht der Krankenblätter zeigte, daß in einer Anzahl von Fällen die arbeitsaufwendige Phänotypisierung tatsächlich zur Diagnose beitrug.

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The Predictive Value of Serum Haptoglobin in Hemolytic Disease

Cited by 90 publications

References 6 publications

‘Haptoglobin concentrations in preterm and term newborns’

‘Haptoglobin concentrations in preterm and term newborns’

CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin

Haptoglobin Typing, is It Clinically Necessary for a Reliable Determination of Haptoglobin with the Single Radial Immunodiffusion Technique?

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