What is the appropriate workup and management for a female patient with a complex hematological picture showing erythrocytosis, microcytic hypochromic anemia, increased Red Cell Distribution Width (RDW), poikilocytosis, basophilic stippling, and polychromasia on her Complete Blood Count (CBC)?

Workup of Microcytic Hypochromic Anemia with Basophilic Stippling and Polychromasia

This presentation suggests iron deficiency anemia with active erythropoiesis (polychromasia indicates reticulocytosis), but the basophilic stippling raises concern for lead toxicity, thalassemia, or sideroblastic anemia that must be systematically excluded. 1

Initial Laboratory Workup

Order the following tests immediately:

• Serum ferritin - This is the single most useful initial test and should be measured first 1, 2
• Transferrin saturation (TSAT) - Essential for distinguishing iron deficiency from other microcytic anemias 1, 2
• Reticulocyte count - The polychromasia on smear suggests elevated reticulocytes, which must be quantified to assess bone marrow response 1
• Peripheral blood smear review - Confirm the basophilic stippling, as this finding is critical for differential diagnosis 3

Interpretation Algorithm

If Ferritin <30 μg/L and TSAT <15-16%:

• Diagnosis: Iron deficiency anemia 1, 2
• The elevated RDW with microcytic hypochromic cells and polychromasia indicates iron-deficient erythropoiesis with active bone marrow response 1
• Investigate the underlying cause immediately - In adult women, consider menstrual losses, but in postmenopausal women or men, gastrointestinal bleeding and malignancy must be excluded 1
• Endoscopic evaluation is required for adult men and postmenopausal women with confirmed iron deficiency 1

If Ferritin Normal or Elevated:

Proceed with additional testing:

• Free erythrocyte protoporphyrin (FEP) - Elevated in iron deficiency, anemia of chronic disease, and lead toxicity; normal in thalassemia 4
• Serum iron level - Low in iron deficiency and chronic disease; normal or elevated in thalassemia and lead toxicity 4
• Blood lead level - Mandatory given the basophilic stippling, which is a hallmark finding of lead toxicity 3, 4
• Hemoglobin electrophoresis - To evaluate for thalassemia trait (elevated HbA2 suggests beta-thalassemia) 2

Critical Diagnostic Considerations

Basophilic Stippling Significance:

The presence of basophilic stippling is not typical of uncomplicated iron deficiency and demands evaluation for:

• Lead toxicity - Basophilic stippling is a classic finding; check blood lead level 3, 4
• Thalassemia - Consider if family history, ethnicity, or persistently low MCV despite iron repletion 2
• Sideroblastic anemia - Rare genetic disorders affecting heme synthesis; consider if other causes excluded 3

Polychromasia Interpretation:

• Polychromasia indicates reticulocytosis and active bone marrow response 3
• This is appropriate in iron deficiency if the patient is responding to treatment or has intermittent bleeding 1
• If reticulocyte count is inappropriately low despite anemia, consider bone marrow dysfunction or myelodysplastic syndrome 3

Addressing the "Erythrocytosis" Component

The term "erythrocytosis" in your question appears contradictory to anemia (low H/H). If you are observing:

• Increased RBC count with low hemoglobin/hematocrit - This suggests microcytic cells where many small RBCs are needed to maintain oxygen-carrying capacity 5
• True erythrocytosis (elevated RBC mass) masked by anemia - Extremely rare but described in polycythemia vera with concurrent iron deficiency or splenic sequestration 5
• If clinical suspicion exists for masked polycythemia vera, check JAK2 mutation and serum erythropoietin level 6

Common Pitfalls to Avoid

• Do not assume iron deficiency based solely on microcytosis - Ferritin can be falsely elevated by inflammation, chronic disease, malignancy, or liver disease 1
• Do not overlook lead toxicity - Basophilic stippling mandates lead level testing, especially with occupational or environmental exposure history 4
• Do not miss thalassemia trait - Patients may have microcytosis disproportionate to anemia severity (MCV often <70 fL) and normal or elevated ferritin 2
• Do not forget to investigate the source of iron loss - Iron deficiency in adults indicates blood loss until proven otherwise 1, 2

Monitoring During Treatment

• Recheck hemoglobin and iron studies after 1-3 months of iron supplementation to assess response 1
• Monitor for iron overload if transfusions or prolonged supplementation required 3
• Persistent microcytosis despite iron repletion warrants hemoglobin electrophoresis for thalassemia 2