What are the diagnostic tests for pernicious (a condition characterized by a deficiency in vitamin B12) anemia?

From the Guidelines

Pernicious anemia should be diagnosed through a combination of blood tests, including vitamin B12 levels, methylmalonic acid, and homocysteine levels, as these are the most sensitive indicators of B12 deficiency 1. When diagnosing pernicious anemia, it is essential to consider the following tests:

• A complete blood count (CBC) to identify macrocytic anemia
• Vitamin B12 levels to confirm deficiency
• Antibody tests for intrinsic factor and parietal cells to identify the autoimmune mechanism
• Methylmalonic acid and homocysteine levels, which become elevated when B12 is deficient, even before anemia develops The Schilling test, although rarely used now, can help determine if the cause is poor absorption 1. Additional tests may include:
• Serum folate levels to rule out folate deficiency
• Gastroscopy with biopsy to check for atrophic gastritis, which commonly accompanies pernicious anemia These tests collectively help establish the diagnosis by confirming B12 deficiency and identifying the autoimmune mechanism that prevents proper B12 absorption, allowing appropriate treatment with B12 supplementation to begin promptly, as highlighted in the recent guideline summary from the BMJ 1.

From the Research

Diagnostic Tests for Pernicious Anemia

• A full blood count (FBC) is often used to investigate pernicious anemia, as it can help identify the condition even in patients who do not exhibit anemic symptoms 2
• Serum vitamin B12 levels can be used to diagnose pernicious anemia, but may not always be reliable due to interference from intrinsic factor antibodies 3
• Other tests that may be used to diagnose pernicious anemia include:
  • Homocysteine and methylmalonic acid levels to identify indirect signs of cobalamin deficiency 3
  • Bone marrow aspirate to identify signs of dyserythropoiesis 3
  • Gastric parietal cell antibodies (GPC) and intrinsic factor antibodies (IFA) to identify autoimmune chronic atrophic gastritis (CAG) 4
• The choice of test may depend on the patient's symptoms and medical history, as well as the presence of other autoimmune diseases 5

Challenges in Diagnosing Pernicious Anemia

• The diagnosis of pernicious anemia can be challenging due to the lack of reliable cobalamin assays and the presence of clinical mimics that simulate other hematological conditions 2
• Intrinsic factor antibodies can interfere with vitamin B12 assays, leading to false normal results 3
• The use of different testing methods, such as competitive binding chemiluminescence (CBLA) and electrochemiluminescence, can affect the accuracy of vitamin B12 measurements 3

Approach to Diagnosis

• A logical approach to the evaluation and diagnosis of anemia is necessary, including the use of complete blood count with red cell indices, reticulocyte count, and testing for specific causes of anemia 6
• Molecular testing may also be used to aid in the diagnostic process 6
• A comprehensive diagnostic workup is essential to identify the underlying cause of anemia and to guide treatment 6, 5