Haptoglobin

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Subject: Haptoglobin

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Definition

  • Haptoglobin is a glycoprotein synthesized mainly in the liver. It sequesters free Hb released from hemolyzed RBCs, which is transported by macrophages to the liver where the heme is broken down to bilirubin. The same function is served by hemopexin and especially albumin. Haptoglobin is also an acute-phase reactant.

  • Normal range: 36–195 mg/dL.

Use

  • Most sensitive test for RBC destruction; absent when the rate of destruction is double that of normal

  • Indicator of chronic hemolysis (e.g., hereditary spherocytosis, PK deficiency, sickle cell disease, thalassemia major, untreated PA).

  • In the diagnosis of transfusion reaction by comparison of concentrations in pretransfusion and posttransfusion samples. In a posttransfusion reaction, the serum haptoglobin level decreases in 6–8 hours; at 24 hours, it is <40 mg/dL or <40% of pretransfusion level.

  • In paternity studies, may aid by determination of haptoglobin phenotypes.

  • Evaluate known or suspected disorders involving a diffuse inflammatory process or tissue destruction, as indicated by elevated levels.

Interpretation

Increased In

  • Conditions associated with increased ESR and α-2 globulin (infections, inflammation, trauma, necrosis of tissue, hepatitis, scurvy, amyloidosis, nephrotic syndrome, disseminated neoplasms such as lymphomas and leukemias, collagen diseases such as rheumatic fever, RA, and dermatomyositis). Therefore, these conditions may mask the presence of concomitant hemolysis.

  • One third of patients with obstructive biliary disease.

  • Therapy with steroids or androgens.

  • Aplastic anemia (normal to very high).

  • DM.

  • Smoking.

  • Aging.

  • Red cell membrane or metabolic defects (G6PD deficiency, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria).

Decreased In

  • Hemoglobinemia (related to the duration and severity of hemolysis) due to

    • Intravascular hemolysis (e.g., hereditary spherocytosis with marked hemolysis, PK deficiency, autoimmune hemolytic anemia, some transfusion reactions)

    • Extravascular hemolysis (e.g., large retroperitoneal hemorrhage)

    • Intramedullary hemolysis (e.g., thalassemia, megaloblastic anemias, sideroblastic anemias)

    • Genetically absent in 1% of white population and 4–10% of the US blacks.

    • Parenchymatous liver disease (especially cirrhosis)

    • Protein loss via the kidney, GI tract, skin

    • Infancy, pregnancy

    • Malnutrition

Limitations

  • Low haptoglobin is normal for the first 3–6 months of life. Haptoglobin is an acute-phase reactant and increases with inflammation or tissue necrosis.

  • Three main phenotypes of haptoglobin are known: Hp 1-1, 2-1, and 2-2. Hp 1-1 circulates as a monomer, and Hp 2-1 and 2-2 are polymers.

  • Significant interlaboratory variations are observed from the sera of healthy individuals.

 
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