What are the appropriate diagnosis and treatment approaches for a patient with suspected anemia?

Diagnosis and Treatment of Anemia

For a patient with suspected anemia, confirm the diagnosis with hemoglobin thresholds (<13.5 g/dL in elderly men, <12.0 g/dL in elderly women and nonpregnant women, <11.0 g/dL in pregnant women), then classify by MCV and systematically identify the underlying cause through iron studies, reticulocyte count, and peripheral smear before initiating targeted treatment. 1

Initial Diagnostic Workup

Confirm anemia using age-appropriate hemoglobin thresholds and obtain a complete blood count with differential and red cell indices as the foundation of your evaluation. 1 A decrease of ≥2 g/dL from baseline warrants investigation even if absolute values remain above anemia thresholds. 1

Classify anemia morphologically by mean corpuscular volume (MCV):

• Microcytic: MCV <80 fL 1
• Normocytic: MCV 80-100 fL 1
• Macrocytic: MCV >100 fL 1

Critical caveat: In dimorphic anemia (combined B12 and iron deficiency), the MCV may be falsely normal due to averaging of large and small cells, making peripheral smear examination essential. 2

Order comprehensive iron studies in all cases:

• Serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), and ferritin 1
• Absolute iron deficiency: TSAT <15% AND ferritin <30 ng/mL 1
• Functional iron deficiency (anemia of chronic disease): ferritin >100 μg/L with TSAT <20% 1

Obtain reticulocyte count and index to assess bone marrow response: low index indicates decreased production, while high index suggests blood loss or hemolysis. 1

Examine peripheral blood smear to confirm RBC morphology and identify specific patterns (microcytes, macrocytes, hypochromic cells, or dimorphic populations). 1, 2

Assess for occult blood loss in stool and urine. 3

Treatment Algorithm by Etiology

Iron Deficiency Anemia

Initiate oral iron supplementation as first-line therapy with ferrous sulfate 324 mg (65 mg elemental iron) daily or twice daily between meals. 1, 3 Add ascorbic acid 250-500 mg twice daily to enhance absorption. 3

Recheck hemoglobin after 4 weeks: An increase in Hb ≥1 g/dL or Hct ≥3% confirms the diagnosis and adequate response. 1, 3 Continue treatment for 2-3 months after hemoglobin normalization to replenish iron stores. 3

Switch to intravenous iron when oral iron is not tolerated, malabsorption is present, or rapid repletion is needed. 1, 3 In cancer patients with severe anemia or those expected to have inadequate oral response, consider IV iron as first-line therapy. 4

Anemia of Chronic Disease/Inflammation

Treat the underlying inflammatory condition as the primary intervention to enhance iron absorption and mobilization. 1, 3 Concurrent iron supplementation is usually necessary despite elevated ferritin levels. 1

Dimorphic Anemia (Combined B12 and Iron Deficiency)

Treat vitamin B12 deficiency first, then add iron supplementation after the reticulocyte crisis appears, typically within 5-10 days of starting B12 therapy. 2 This sequential approach prevents masking the B12 deficiency response and optimizes erythropoiesis.

For pernicious anemia specifically, parenteral vitamin B12 is required for life: 100 mcg daily for 6-7 days by intramuscular or deep subcutaneous injection, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life. 5 The oral form is not dependable for pernicious anemia. 5

Cancer-Related Anemia

Evaluate for multiple potential causes including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin deficiency from renal disease, and marrow involvement with tumor. 4, 3

Screen for renal function prior to myelosuppressive chemotherapy. 3 In patients with GFR <30 ml/min per 1.73 m², monitor hemoglobin at least every three months. 4

For patients with GFR <30 ml/min per 1.73 m² and hemoglobin <12 g/dL (women) or <13 g/dL (men), perform complete workup for anemia including iron studies. 4 If iron deficiency is identified, treat it. 4 If anemia persists despite appropriate evaluation and iron therapy, treat with erythropoietin or analogue. 4

Consider ESAs only for patients receiving palliative myelosuppressive chemotherapy with Hb <10 g/dL and without absolute iron deficiency. 4, 3 ESAs are not indicated for patients receiving chemotherapy when the anticipated outcome is cure. 4 Use subcutaneous rather than IV route for better efficacy. 4

Important safety consideration: ESAs carry risks including hypertension, thromboembolism, and potential tumor progression in cancer patients. 3 Iron repletion must be verified before considering ESAs. 2

Transfusion Strategy

Reserve red blood cell transfusion for severe symptomatic anemia with hemodynamic instability. 2, 3 Use a restrictive transfusion strategy with a hemoglobin threshold of 7-8 g/dL in stable, non-cardiac patients, including those with coronary heart disease. 2, 3

One unit of packed red cells increases hemoglobin by approximately 1 g/dL in an average-sized adult who is not bleeding. 4

Critical pitfall: Transfusion does not address underlying deficiencies and should not replace definitive treatment with vitamin supplementation and iron repletion. 2 The iron in transfused red cells (147-278 mg per unit) is not immediately available for erythropoiesis, as the average lifespan of a transfused red cell is 100-110 days. 4 Pre-transfusion iron indices are recommended to guide subsequent iron therapy. 4

Monitoring and Follow-up

Monitor hemoglobin and RBC indices every 3 months for 1 year, then annually after initiating treatment. 2, 3 Administer additional iron supplementation if hemoglobin or MCV fall below normal. 3

For chronic kidney disease patients, continue hemoglobin monitoring every 3 months. 1 Monitor for anemia recurrence, which occurs in >50% of patients within one year. 1

For dimorphic anemia, recheck hemoglobin after 4 weeks of combined therapy, expecting an increase of ≥1 g/dL or Hct ≥3%. 2

Special Populations

Pregnant women: Start oral, low-dose (30 mg/day) iron supplementation at the first prenatal visit and screen for anemia using stage-specific criteria. 1

Infants and children: Treat presumptive iron-deficiency anemia with 3 mg/kg per day of iron drops administered between meals, and counsel parents about adequate dietary iron intake. 1

Key Pitfalls to Avoid

Never treat anemia empirically without identifying the underlying cause, as failure to address the etiology leads to recurrence in >50% of patients. 1, 3 The American Society of Hematology emphasizes treating the etiology, not simply the hemoglobin number. 1

Do not overlook dimorphic anemia when MCV appears normal—always examine the peripheral smear for mixed cell populations. 2

Avoid overreliance on transfusions rather than addressing the underlying cause, as transfusion carries risks including iron overload, infection transmission, immune suppression, and increased thrombosis risk. 4, 3

Do not use ESAs without considering contraindications and ensuring iron repletion is adequate. 2, 3