What is the recommended workup and management for a patient presenting with symptoms of anemia, such as fatigue, weakness, and shortness of breath, considering their medical history, physical examination findings, and demographic information, including age and sex?

Anemia Workup

Begin with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies (serum ferritin, transferrin saturation, total iron-binding capacity), and inflammatory markers (C-reactive protein) as your essential first-line laboratory panel. 1, 2, 3

Diagnostic Thresholds

• Anemia is defined as hemoglobin < 13 g/dL in men, < 12 g/dL in non-pregnant women, and < 11 g/dL in pregnant women 1, 2, 3
• These thresholds should trigger immediate workup when symptoms such as fatigue, weakness, or shortness of breath are present 4, 5

Initial Laboratory Evaluation

Order all of the following tests simultaneously at initial presentation:

• Complete blood count with red cell indices (MCV, MCH, MCHC) 1, 2, 3
• Reticulocyte count to assess bone marrow response 1, 2, 3
• Iron studies panel: serum ferritin, transferrin saturation, and total iron-binding capacity 1, 2, 3
• C-reactive protein to assess for inflammation 2, 3

Morphologic Classification and Next Steps

Microcytic Anemia (MCV < 80 fL)

• Iron deficiency anemia is the most common cause 1, 2, 3
• Confirm iron deficiency with serum ferritin < 30 μg/L and transferrin saturation < 15% in the absence of inflammation 1, 3
• Critical pitfall: Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease—interpret in clinical context 2, 3
• If iron studies are normal, consider thalassemia trait (obtain hemoglobin electrophoresis, particularly in patients of Mediterranean, African, or Southeast Asian descent), anemia of chronic disease, or sideroblastic anemia 1, 3

Normocytic Anemia (MCV 80-100 fL)

• Consider acute blood loss, hemolysis, anemia of chronic disease, early iron deficiency, or chronic kidney disease 2, 3
• If ferritin is low despite normal MCV, this still indicates iron deficiency 1, 3
• For suspected hemolysis, measure haptoglobin, LDH, and bilirubin 3
• Low or normal reticulocyte count indicates impaired erythropoiesis; elevated reticulocyte count suggests increased red cell production in response to blood loss or hemolysis 3

Macrocytic Anemia (MCV > 100 fL)

• Measure vitamin B12 and folate levels 2, 3
• Consider medications, alcohol use, or myelodysplastic syndrome as additional causes 2, 3
• Critical pitfall: High-dose folic acid supplementation may mask vitamin B12 deficiency symptoms—always check B12 before treating with folate 1, 3

Special Attention to Combined Deficiencies

• Watch for combined deficiencies (iron plus B12, or iron plus folate), especially in elderly patients and those with inflammatory bowel disease 1, 2
• Elevated RDW with normal or low-normal MCV suggests early iron deficiency or mixed nutritional deficiencies 3
• Low MCH is a more reliable marker of iron deficiency than MCHC and may indicate iron-deficient erythropoiesis even before frank anemia develops 3

Evaluation for Underlying Causes

• In adult men and postmenopausal women with confirmed iron deficiency, endoscopy is warranted to evaluate for gastrointestinal malignancy 4
• In premenopausal women, assess for menstrual blood loss 3
• For anemia of chronic disease, address the underlying inflammatory condition 3

Chronic Kidney Disease Considerations

• Monitor hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 2
• Initiate workup when hemoglobin < 12 g/dL in adult males and postmenopausal females, or < 11 g/dL in premenopausal females 2
• Treat identified iron deficiency first before considering erythropoietin therapy 1, 2
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 1

Treatment Principles

• Oral iron supplementation is first-line treatment for iron deficiency anemia 1
• Parenteral iron is reserved for patients who cannot tolerate or absorb oral preparations, or when rapid repletion is needed 1, 3
• For vitamin B12 deficiency, use intramuscular or deep subcutaneous cyanocobalamin with monthly maintenance doses for life 1
• Folate deficiency should be treated with oral folate supplementation, but always exclude B12 deficiency first 1
• Normalization of hemoglobin typically occurs by 8 weeks after treatment in most patients with iron deficiency 4

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 1, 2
• Do not rely on a single hemoglobin measurement—trends matter more than isolated values 6
• Avoid treating empirically without establishing the specific cause of anemia 4, 5
• Consider transfusion for symptomatic patients with hemoglobin ≤ 8 g/dL, particularly if experiencing severe fatigue, dizziness, or hypotension 3, 4