From the Guidelines
Pernicious anemia is characterized by macrocytic anemia with an elevated mean corpuscular volume (MCV) typically above 100 fL, indicating a megaloblastic anemia due to vitamin B12 or folate deficiency. The laboratory signs of pernicious anemia can be identified using a morphologic approach, which characterizes anemia based on the MCV 1.
Key Laboratory Findings
- Macrocytic anemia with MCV above 100 fL
- Decreased vitamin B12 levels
- Hypersegmented neutrophils and macro-ovalocytes on blood smears
- Decreased hemoglobin and hematocrit values
- Elevated homocysteine and methylmalonic acid levels
- Reduced reticulocyte counts despite anemia
- Megaloblastic changes on bone marrow examination
- Presence of anti-intrinsic factor antibodies and anti-parietal cell antibodies
- Mild thrombocytopenia and leukopenia may also be present
These laboratory findings are consistent with the diagnosis of pernicious anemia, which is caused by a deficiency in vitamin B12 due to insufficient uptake or inadequate absorption through lack of intrinsic factor 1.
Diagnostic Approach
The kinetic approach to evaluating anemia focuses on the underlying mechanism, distinguishing among production, destruction, and loss of red blood cells 1.
- A low reticulocyte index (RI) indicates decreased red blood cell production, suggesting iron deficiency, vitamin B12/folate deficiency, or bone marrow dysfunction
- A high RI indicates normal or increased red blood cell production, suggesting blood loss or hemolysis
- Additional tests, such as iron and total iron binding capacity (TIBC), vitamin B12 or folate levels, and stool guaiac, can help identify the underlying cause of anemia 1.
From the Research
Laboratory Signs of Pernicious Anemia
The laboratory signs of pernicious anemia can be identified through various tests, including:
- Total plasma vitamin B12
- Plasma homocysteine
- Plasma methylmalonic acid (pMMA) concentration
- Urinary methylmalonic acid-to-creatinine ratio
- Full blood count (FBC)
- Holotranscobalamin (HoloTC)
Biomarkers for B12 Deficiency
Several biomarkers are used to diagnose B12 deficiency, including:
- Vitamin B12 (B12)
- Holotranscobalamin (HoloTC)
- Methylmalonic acid (MMA)
- Homocysteine (Hcy) These biomarkers have different diagnostic accuracy, with HoloTC and MMA being more sensitive than B12 and Hcy in detecting subclinical B12 deficiency 2.
Diagnostic Challenges
Pernicious anemia can be challenging to diagnose due to its complex and diverse clinical presentations, as well as the lack of reliable cobalamin assays 3, 4. Additionally, normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, making it essential to use multiple biomarkers to diagnose B12 deficiency 5.
Treatment and Monitoring
Oral vitamin B12 supplementation can improve vitamin B12 deficiency in pernicious anemia, with significant improvements in plasma vitamin B12, plasma homocysteine, and pMMA concentrations 6. Regular monitoring of these biomarkers is essential to assess the efficacy of treatment and adjust the dosage as needed.