Macrocytic Anemia: Pernicious Anemia Overview

Macrocytic Anemia (2)

• Pernicious anemia is a specific type of megaloblastic anemia caused by a lack of intrinsic factor (IF), which is an autoimmune condition.
• It is an uncommon disease that typically affects people over 40.

Pernicious Anemia Pathogenesis

• Pernicious anemia is an immunologically mediated condition.
• Three types of antibodies are involved:
  • Type I antibody (50%): Blocks vitamin B12 and IF binding.
  • Type II antibody (35%): Prevents the binding of the IF-B12 complex to ileal receptors.
  • Type III antibody (85-90%): Targets specific structures in parietal cells.
• Pernicious anemia can be associated with other autoimmune diseases such as autoimmune thyroiditis.

Pernicious Anemia Diagnosis

• Gastric analysis is used to diagnose pernicious anemia.
• The Schilling test is a diagnostic tool. It involves administering radioactive vitamin B12 orally and measuring levels in the urine. A follow-up test, with intrinsic factor, is performed. Results determine if the absorption issue is related to the absence of intrinsic factor.
• Serum cobalamin levels are also measured.

Schilling Test Details

• Part 1: Oral radioactive vitamin B12 and intramuscular unlabeled vitamin B12 are administered simultaneously.
• Part 2: If Part 1 shows low absorption, repeat administration with oral intrinsic factor to determine if it resolves the issue.
• Results: Normal results on both parts suggest vitamin B12 deficiency, not pernicious anemia. Low result on the second part and normal on the first shows malabsorption, or possibly pernicious anemia, and further investigation is needed.

Other Macrocytic Anemias

• There are various non-megaloblastic causes for macrocytic anemia.
• The specific mechanisms for large red blood cells formation are often unclear, although lipid deposition on red blood cell membranes or changes to erythroblast maturation times might be involved.

Causes of Macrocytosis

• Alcohol-related issues
• Liver disease
• Myxedema
• Myelodysplastic syndromes
• Cytotoxic drugs
• Aplastic anemia
• Pregnancy
• Smoking
• Reticulocytosis
• Myeloma and paraproteinemia
• Neonatal conditions