Acute Phase Protein – Part 3 – Haptoglobin

Acute-phase protein (Acute Phase Reactants)

• Acute-phase protein is raised in inflammatory conditions.
• When there is an increase in a protein called positive acute-phase protein.
  • In the case of a decrease in the acute phase protein, is called negative phase protein.
• The acute phase proteins (positive) are protein whose concentration increases in the plasma and after the disease episode is over then it decreases and may become normal.

Haptoglobin

Sample

1. The blood sample of the patient is needed.
2. The serum is needed to perform the test.
3. Can store for 2 weeks at -20 °C.

Indication

• This test is done to detect intravascular hemolysis.

Precaution

• Avoid the hemolyzed sample.

Pathophysiology

1. This is an α-2 glycoprotein and binds Hemoglobin irreversibly.
   1. This is a free Hb binding protein.
   2. Transport the free hemoglobin through the blood to the liver for degradation.
      1. Free hemoglobin is bound to the α-chain of the haptoglobin.
   3. This is present in the α-2 zone on electrophoresis. 
   4. Haptoglobin increases from the mean value of 0.02g/L at birth to an adult level within the first year of life.
      1. It increases with the increasing age.
2. This is synthesized in the liver and consists of four peptide chains linked by a disulfide bond.
   1. There is three possible alpha (α) chains and only one β-chain.

3. It binds free hemoglobin and is rapidly cleared from the blood in case of intravascular hemolysis.
   1. In the initial stage of the hemolysis, the liver can compensate for the synthesis of HP, so its level is decreased.
4. This is an increase in acute and chronic inflammation.
5. It is a natural bacteriostatic agent for iron-requiring bacteria e.g. E.coli.
6. This is acute-phase protein increased in ulcerative colitis, acute rheumatic diseases and heart attack.
7. This is helpful to differentiate hemolytic anemia from the other causes of anemia.
   1. Haptoglobin is markedly increased plus when Reticulocytes are increased indicates intravascular hemolysis.
      1. Intravascular hemolysis = Increased haptoglobin +  Increased reticulocytes.
   2. Haptoglobin is normal or slightly decreased plus Reticulocytes are increased indicate extravascular hemolysis in the liver or spleen.
      1. Extravascular hemolysis = Haptoglobin normal + Increased reticulocytes.
   3. Haptoglobin is normal plus Reticulocytes are not increased indicate decreased production of the RBC from bone marrow.
      1. Bonemarrow depression = Haptoglobin normal + reticulocytes not increased.
   4. Haptoglobin depletion is a sensitive marker for the hemolysis.
   5. HP is decreased in the hemoglobinuria.
   6. HP is unchanged in the myoglobinuria and rhabdomyolysis because there is no binding with HP.

Normal

• Newborn          =  5 to 48 mg/dL
  • 6 months to 16 years = 25 to 138 mg/dL
• 16 to 60 years  = 15 to 200 mg/dL
• >60 years          =  35 to 175 mg/dL
• Another source
  • Adult = 20 to 220 mg/dL
  • Newborn = 0 to 10 mg/dL
• Critical value  = <40 mg /dL

The increased  level is seen in:

1. By corticosteroid hormones and nonsteroidal anti-inflammatory drugs.
2. In nephrotic syndrome.
3. In biliary obstruction in the absence of hepatocellular disease.
4. Ulcerative colitis.
5. peptic ulcer.
6. Acute rheumatic disease.
7. In cancers.
8. In acute and chronic inflammatory diseases and it acts as acute-phase protein.
9. In acute myocardial infarction.
10. In tissue destruction like burn, and cancers.
11. Drugs that may increase the level are:
    1. Steroids.
    2. Androgens.

The decreased level is seen in:

1. In hemolytic anemia.
2. Systemic lupus erythematosus
3. Erythroblastosis fetalis.
4. Estrogen will decrease its synthesis.
5. Decreased with severe liver diseases.
6. The slight decrease in blood transfusion even in the compatible blood transfusion due to the presence of a few RBC hemolysis.
7. This may be decreased in hematoma because of the binding of Hb with HP.
8. Drugs that may decrease the level are:
   1. Chlorpromazine.
   2. Isoniazid.
   3. Oral contraceptives.
   4. Streptomycin.
   5. Quinidine.
   6. Nitrofurantoin.

Critical value is <40 mg/dL.

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