Anemia: Diagnosis and Management
The diagnosis of anemia should be based on morphological classification (microcytic, normocytic, or macrocytic) and evaluation of iron parameters, reticulocytes, and other specific tests to determine the underlying etiology. 1
Definition and Classification
- Anemia is defined as hemoglobin below normal values: less than 13 g/dL in men and less than 12 g/dL in women 2
- Morphological classification based on mean corpuscular volume (MCV) is fundamental for differential diagnosis 1:
- Microcytic (MCV < 80 fL): iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia
- Normocytic (MCV 80-100 fL): acute blood loss, hemolysis, renal failure, anemia of chronic disease, bone marrow failure
- Macrocytic (MCV > 100 fL): vitamin B12/folate deficiency, alcoholism, myelodysplastic syndrome, drug-induced
Diagnostic Approach
- Complete blood count with reticulocyte count is essential for initial evaluation 1, 2
- Reticulocyte index (RI) helps distinguish between production and destruction/loss problems 3:
- Low RI (<1.0): decreased production (iron deficiency, vitamin deficiencies, bone marrow dysfunction)
- High RI (>2.0): blood loss or hemolysis 3
- Iron studies are crucial for diagnosis 1:
- Additional tests based on initial findings 3, 1:
- Vitamin B12/folate levels for macrocytic anemia
- Hemolysis workup: Coombs test, haptoglobin, bilirubin
- Kidney function tests for suspected renal anemia
- Bone marrow evaluation for unexplained cases or suspected marrow infiltration
Common Types of Anemia and Management
Iron Deficiency Anemia
- Most common type of anemia worldwide, affecting approximately 2 billion people 4
- Causes: bleeding (menstrual, gastrointestinal), impaired absorption, inadequate intake, pregnancy 4
- Diagnosis: low ferritin (<30 ng/mL) or transferrin saturation <20% 4
- Treatment 4, 5:
- Oral iron: ferrous sulfate 325 mg daily or on alternate days
- Continue treatment for 3-6 months to replenish iron stores
- Investigate and treat underlying cause (especially GI bleeding in men and postmenopausal women)
- Intravenous iron for oral intolerance, malabsorption, or ongoing blood loss
Anemia of Chronic Disease
- Second most common type of anemia globally 6
- Associated with chronic inflammation, autoimmune diseases, cancer, kidney failure 6
- Laboratory findings: mild-moderate anemia, low iron, low transferrin, elevated ferritin 6
- Treatment 3, 6:
- Address underlying condition
- Iron supplementation if concurrent iron deficiency exists
- Consider erythropoiesis-stimulating agents in selected cases
Vitamin B12 Deficiency Anemia
- Causes: pernicious anemia, malabsorption, inadequate intake 7
- Treatment for pernicious anemia 7:
- Intramuscular vitamin B12 100 mcg daily for 6-7 days
- Then alternate days for 7 doses, then every 3-4 days for 2-3 weeks
- Maintenance: 100 mcg monthly for life
- Avoid intravenous route (vitamin will be lost in urine)
Cancer-Related Anemia
- Multifactorial etiology: myelosuppression, blood loss, functional iron deficiency, erythropoietin deficiency 3
- Treatment options 3:
- Iron therapy (especially for functional iron deficiency)
- Erythropoiesis-stimulating agents (with restrictions)
- Red blood cell transfusions
- Address underlying causes when possible
Special Considerations
- Genetic anemias: Consider in patients with microcytic anemia refractory to iron treatment 1, 3
- Unexplained anemia with iron deficiency: Evaluate for gastrointestinal malignancy with bidirectional endoscopy (except in premenopausal women <40 years) 8
- Pregnancy: Iron deficiency affects up to 84% of women in third trimester; consider IV iron in second and third trimesters 4
- Chronic kidney disease: Evaluate renal function and consider erythropoiesis-stimulating agents 2