Initial Workup for Low Hemoglobin (Hypochromic Anemia)
The initial step in managing a patient with low hemoglobin is to measure serum ferritin, which is the most powerful test for iron deficiency, along with complete blood count with red cell indices, and screening for coeliac disease in all patients. 1
Essential Laboratory Tests
The diagnostic workup should include:
Serum ferritin: This is the most powerful single test for diagnosing iron deficiency 1. A level <15 μg/L indicates absolute iron deficiency 1. However, ferritin is an acute-phase reactant, so in the presence of inflammation (elevated CRP or ESR), the threshold increases to <100 μg/L 1.
Complete blood count with red cell indices: Red cell indices provide sensitive indication of iron deficiency in the absence of chronic disease or haemoglobinopathy 1. Hypochromic microcytic anemia is the typical pattern.
Transferrin saturation (TfS): A level <16% is a sensitive marker of iron deficiency, though specificity is only 40-50% 1. When TfS is <16% and ferritin is between 30-100 μg/L in the presence of inflammation, hypoferraemia should be considered likely 1.
Inflammatory markers (CRP, ESR): These are essential because they affect interpretation of ferritin and transferrin levels 1. The evaluation of anemia is incomplete if inflammatory status is not clearly defined 1.
Coeliac disease screening: All patients with iron deficiency anemia should be screened for coeliac disease 1, as malabsorption from coeliac disease is one of the most important gastrointestinal causes requiring identification 1.
Additional Testing Based on Clinical Context
Vitamin B12 and folate levels: Should be checked at least annually, or if macrocytosis is present 1. These should be evaluated in patients with hypochromic anemia 2.
Renal function (creatinine, GFR): Check for occult renal insufficiency 2, as chronic kidney disease is a common cause of anemia 1.
Haemoglobin electrophoresis: Recommended when microcytosis and hypochromia are present in patients of appropriate ethnic background to prevent unnecessary gastrointestinal investigation 1.
Critical Interpretation Points
In the absence of inflammation (normal CRP/ESR):
In the presence of inflammation (elevated CRP/ESR):
- Ferritin threshold increases to <100 μg/L 1
- Ferritin >100 μg/L with TfS <16% suggests anemia of chronic disease 1
- Ferritin between 30-100 μg/L with TfS <16% suggests likely hypoferraemia 1
Age and Gender-Specific Considerations
Postmenopausal women and all men: Upper and lower gastrointestinal investigations should be considered unless there is significant overt non-gastrointestinal blood loss 1. These patients should not be routinely screened but should be evaluated with gastrointestinal endoscopy when iron deficiency anemia is diagnosed 3.
Premenopausal women: All should be screened for coeliac disease, but other upper and lower gastrointestinal investigations should be based on clinical judgment 1. Women should be screened during pregnancy 3.
Children: Should be screened at one year of age 3.
Common Pitfalls to Avoid
Do not rely on ferritin alone in inflammatory states: Ferritin can be falsely elevated by inflammation, masking true iron deficiency 1. Always measure inflammatory markers concurrently.
Do not use faecal occult blood testing: This is of no benefit in the investigation of iron deficiency anemia 1.
Do not skip coeliac screening: This is required in all patients with iron deficiency anemia, as it is a treatable cause that will prevent response to iron therapy if missed 1.
Do not ignore the severity of anemia: The lower the hemoglobin, the more likely there is serious underlying pathology and the more urgent the need for investigation 1.