How should I evaluate and manage an adult with low hemoglobin and hematocrit (anemia)?

Evaluation and Management of Low Hemoglobin and Hematocrit in Adults

Begin with a complete blood count (CBC) with red cell indices, reticulocyte count, and iron studies (serum ferritin and transferrin saturation) to classify the anemia and guide targeted investigation based on mean corpuscular volume (MCV). 1

Define Anemia Using Gender-Specific Thresholds

Diagnose anemia when hemoglobin falls below 13.5 g/dL in adult males or 12.0 g/dL in adult females. 2 These thresholds are based on the 5th percentile from NHANES III data and should trigger systematic evaluation. 2

Important caveat: These standard definitions may not apply to:

• Pregnant or menstruating women 2
• Individuals living at high altitude 2
• Smokers 2
• Men ≥70 years of age 2
• Non-Caucasian populations 2
• Patients with chronic lung disease or hemoglobinopathy 2

Initial Laboratory Evaluation

Obtain these tests immediately:

• Complete blood count with differential to assess all three cell lines (white blood cells, hemoglobin, platelets). 2 Abnormalities in two or more cell lines warrant hematology consultation. 2

• Reticulocyte count to distinguish inadequate bone marrow production (low count) from hemolysis or blood loss (elevated count). 2, 1 A low reticulocyte count in CKD patients replete with iron, folate, and B12 typically indicates insufficient erythropoietin production or inflammation. 2

• Iron studies: serum ferritin (tissue iron stores) and transferrin saturation (iron available for erythropoiesis). 2, 3 Critical pitfall: Ferritin is an acute phase reactant and may be falsely elevated in inflammatory states despite true iron deficiency—consider iron deficiency even with ferritin 30-100 μg/L if inflammation is present. 1, 4

• Kidney function tests to evaluate for chronic kidney disease as a cause. 3, 4

• Vitamin B12 and folate levels to rule out nutritional deficiencies. 1

Classification by MCV and Targeted Investigation

Microcytic Anemia (MCV <80 fL)

If ferritin <45 ng/mL: Diagnose iron deficiency anemia. 1

• Initiate oral iron supplementation as first-line therapy (50-100 mg elemental iron daily or on alternate days). 3, 1, 5 New evidence shows intermittent dosing is as effective as daily dosing with fewer side effects. 5

• Evaluate for gastrointestinal bleeding: Perform bidirectional endoscopy in all men and postmenopausal women with iron deficiency anemia to evaluate for malignancy. 1 Test for H. pylori and celiac disease non-invasively before endoscopy. 1

• Use intravenous iron for patients with intolerance to oral iron, chronic kidney disease with poor oral response, or inflammatory bowel disease. 3, 1

If ferritin is normal or elevated: Consider thalassemia, anemia of chronic disease, or sideroblastic anemia. 1

Normocytic Anemia (MCV 80-100 fL)

Evaluate for anemia of chronic disease, renal failure, or endocrine disorders. 3

Characteristic findings of anemia of chronic disease:

• Low serum iron, low or normal transferrin, low transferrin saturation, normal or elevated ferritin 4
• Low reticulocyte count 4
• Treatment focuses on the underlying condition 4

For chronic kidney disease patients:

• Screen yearly at minimum for anemia 2
• More frequent monitoring (every 3 months) for diabetic patients, who develop anemia at earlier CKD stages 2, 3
• Erythropoiesis-stimulating agents may be considered in severe or symptomatic anemia 3, 4

Macrocytic Anemia (MCV >100 fL)

Evaluate for vitamin B12 or folate deficiency, hypothyroidism, or myelodysplasia. 3

• Treat vitamin B12 deficiency immediately with hydroxocobalamin 1 mg intramuscularly. 1
• Never start folic acid before excluding B12 deficiency to prevent irreversible neurological complications. 1

Transfusion Thresholds

Reserve blood transfusions for:

• Hemoglobin ≤5.1 g/dL with hemodynamic instability or severe symptoms 1
• Symptomatic patients with hemoglobin ≤8 g/dL 1

Monitoring and Follow-Up

• Confirm iron stores are restored after hemoglobin normalizes by rechecking ferritin. 1
• Hemoglobin is preferred over hematocrit for monitoring because it is more reproducible across laboratories and not affected by storage time or patient-specific variables like serum glucose. 2
• Regular monitoring every 3 months is recommended for patients with chronic kidney disease. 3