From the Guidelines
The workup for pernicious anemia should include complete blood count (CBC), vitamin B12 levels, methylmalonic acid (MMA), homocysteine levels, and intrinsic factor antibodies. When evaluating a patient with suspected pernicious anemia, it is crucial to consider the potential for neurological involvement, as seen in vitamin B12 deficiency with possible neurological symptoms, such as unexplained sensory and/or motor and gait symptoms, where vitamin B12 deficiency should be treated immediately and urgent specialist advice sought from a neurologist and haematologist 1. The diagnostic approach typically involves:
- Complete blood count (CBC) to identify macrocytic anemia with elevated mean corpuscular volume (MCV) and decreased hemoglobin
- Vitamin B12 levels, with low serum B12 levels (<200 pg/mL) being diagnostic
- Methylmalonic acid (MMA) and homocysteine levels to provide additional confirmation when B12 levels are borderline
- Intrinsic factor antibodies, which are highly specific for pernicious anemia, present in about 50-70% of cases
- Anti-parietal cell antibodies may also be checked but are less specific Treatment of pernicious anemia involves vitamin B12 replacement, and according to the most recent guidelines, hydroxocobalamin 1 mg intramuscularly should be administered three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2–3 months for life 1. It is essential to monitor patients with repeat CBC and B12 levels to ensure adequate response to therapy and prevent irreversible neurological complications such as subacute combined degeneration of the spinal cord. In cases where neurological involvement is suspected, hydroxocobalamin 1 mg intramuscularly should be administered on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly administered every 2 months 1. Early diagnosis and treatment are critical to prevent long-term complications and improve quality of life.
From the FDA Drug Label
Hematocrit, reticulocyte count, vitamin B12, folate and iron levels should be obtained prior to treatment. Hematocrit and reticulocyte counts should be repeated daily from the fifth to seventh days of therapy and then frequently until the hematocrit is normal. If folate levels are low, folic acid should also be administered If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated. Repeat determinations of iron and folic acid may reveal a complicating illness that might inhibit the response of the marrow Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as the general population, so appropriate tests for this condition should be carried out when indicated.
The workup for pernicious anemia includes:
- Initial laboratory tests:
- Hematocrit
- Reticulocyte count
- Vitamin B12 levels
- Folate levels
- Iron levels
- Monitoring during treatment:
- Daily hematocrit and reticulocyte counts from the fifth to seventh days of therapy
- Frequent hematocrit and reticulocyte counts until the hematocrit is normal
- Additional tests:
- Folic acid administration if folate levels are low
- Repeat iron and folic acid determinations to rule out complicating illnesses
- Tests for carcinoma of the stomach due to the increased incidence in patients with pernicious anemia 2
From the Research
Diagnostic Approach
The workup for pernicious anemia involves several steps, including:
- Full blood count (FBC) to investigate anemia 3
- Serological markers such as increased fasting gastrin and decreased pepsinogen I to suggest oxyntic mucosa damage 4
- Intrinsic factor and parietal cell antibodies as surrogate markers of pernicious anemia, with 73% sensitivity and 100% specificity 4
- Schilling's test to prove intrinsic factor deficiency, although this may not always be necessary 4
- Bone marrow aspiration to reveal megaloblastic changes of erythroid cells and multilineage dysplasia 5
- Blood smear to reveal hypersegmented neutrophils 5
Diagnostic Challenges
The diagnosis of pernicious anemia can be challenging due to:
- Lack of reliable cobalamin assays to diagnose cobalamin deficiency 3
- Clinical mimics that simulate other hematological conditions, such as myelodysplastic syndrome, acute leukemia, and sideroblastic anemias 3, 6
- Possibility of falsely normal or falsely elevated vitamin B12 levels in the presence of anti-intrinsic factor antibodies 5
- Diverse clinical manifestations, including spuriously normal or high cobalamin levels, normocytic or microcytic anemia, and non-anemic macrocytosis 6
Laboratory Findings
Laboratory findings that may indicate pernicious anemia include:
- Severe pancytopenia with macrocytosis, low reticulocyte count, and marked signs of hemolysis 7
- Very low serum level of vitamin B12 7
- Chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum 7
- Hypersegmented neutrophils and megaloblastic changes of erythroid cells on bone marrow aspiration 5