From the Guidelines
For a patient with low hemoglobin, beyond the initial CBC, CMP, and type and cross-match, iron studies (serum iron, ferritin, total iron binding capacity, transferrin saturation) are strongly recommended as the first-line additional diagnostic tests. According to the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1, serum ferritin is the single most useful marker of iron deficiency anaemia (IDA), and other blood tests such as transferrin saturation can be helpful if a false-normal ferritin is suspected.
The ESPEN micronutrient guideline 2 also supports the investigation of iron deficiency using a combination of tests including plasma iron, transferrin, transferrin saturation, ferritin, CRP, hepcidin, and evaluation of red blood cell morphology, with a strong consensus of 97%.
Key additional diagnostic studies to consider include:
- Vitamin B12 and folate levels to evaluate for vitamin deficiencies
- Reticulocyte count to assess bone marrow response
- Peripheral blood smear to evaluate red blood cell morphology
- Hemoglobin electrophoresis to diagnose hemoglobinopathies
- Erythropoietin levels to evaluate for inadequate erythropoietin production
Further testing may be guided by the results of these initial studies, and may include:
- Direct Coombs test to evaluate for hemolytic anemia
- Lactate dehydrogenase (LDH) and haptoglobin to assess for hemolysis
- Stool guaiac or fecal immunochemical testing to check for gastrointestinal bleeding
- Bone marrow aspiration and biopsy in certain cases to evaluate for myelodysplastic syndromes, leukemia, or other bone marrow disorders.
From the Research
Diagnostic Studies for Low Hemoglobin
The following diagnostic studies are recommended for a patient with low hemoglobin, in addition to Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), and type and cross-match:
- Serum ferritin levels to diagnose iron deficiency anemia, as it is considered the gold standard with a specificity of 99% and sensitivity of 80% at a concentration of 30 ng/ml 3
- Transferrin saturation, which can be determined by dividing serum iron by Total Iron Binding Capacity (TIBC) and multiplying by 100, although its diagnostic accuracy is limited 3
- Further evaluation of the patient's history and laboratory values to develop a practical differential diagnosis of the cause of the low hemoglobin level, using a systematic approach and algorithm to navigate the diagnostic process 4
Additional Recommendations
- Performing a complete blood count on a yearly basis is recommended for patients with an underlying chronic condition, for men ≥ 50 years old, and for all women with no chronic condition on an every-5-years basis 5
- Observation alone may be recommended based on age, gender, and hemoglobin level, while an empiric trial of iron may be inappropriate for women over age 40 and for all men 5
- Erythropoietic growth factors may be recommended based on hemoglobin level and anemia symptoms, and transfusion may be recommended based on the severity of anemia and the presence of cardiovascular disease 5