What is the management approach for a patient with anemia characterized by low Red Blood Cell (RBC) count, low hemoglobin, and low Red Cell Distribution Width (RDW)?

Management of Anemia with Low RBC, Low Hemoglobin, and Low RDW

A low RDW with anemia strongly suggests thalassemia trait or anemia of chronic disease rather than iron deficiency, and you must confirm the diagnosis with serum ferritin, hemoglobin electrophoresis, and inflammatory markers before initiating any treatment. 1

Understanding the Laboratory Pattern

The combination of low hemoglobin with low (or normal) RDW is diagnostically significant because it narrows your differential considerably:

• Low RDW (≤14.0%) makes iron deficiency anemia unlikely, as iron deficiency typically presents with elevated RDW (>14.0%) due to heterogeneous red cell populations at different stages of iron depletion 1
• Thalassemia trait characteristically shows low MCV with low RDW because the microcytic cells are homogeneous in size 1
• Early anemia of chronic disease may present with normal MCV and low RDW, reflecting the body's inability to utilize stored iron 1

Essential Diagnostic Workup

First-Line Laboratory Tests

Obtain these tests immediately to establish the etiology:

• Serum ferritin: <30 μg/L indicates iron deficiency in the absence of inflammation; however, ferritin can be falsely elevated up to 100 μg/L in patients with concurrent inflammation, malignancy, or hepatic disease 2, 1
• Complete blood count with MCV: Low MCV with low RDW strongly suggests thalassemia minor; normal MCV with low RDW suggests anemia of chronic disease 1
• C-reactive protein (CRP): Essential to identify inflammation that may elevate ferritin and mask iron deficiency 1
• Transferrin saturation: <30% supports iron deficiency 2, 1
• Reticulocyte count: Assesses bone marrow response to anemia 1

Second-Line Testing Based on Initial Results

• Hemoglobin electrophoresis: Mandatory if thalassemia is suspected based on ethnicity, low MCV with normal/low RDW, or elevated red cell count despite anemia 1
• Vitamin B12 and folate levels: Combined deficiencies (iron plus folate or B12) can result in normal MCV despite iron deficiency, which may be recognized by RDW patterns 2, 1

Critical Diagnostic Pitfalls to Avoid

Do NOT Assume Iron Deficiency

• Never empirically treat with iron based solely on low hemoglobin—low RDW makes iron deficiency less likely, not more likely 1
• Do not give iron supplementation to patients with thalassemia trait unless concurrent iron deficiency is documented by ferritin testing, as this can cause iron overload 1

Do NOT Overlook Combined Deficiencies

• Microcytosis and macrocytosis can coexist, resulting in normal MCV but abnormal RDW patterns 1
• Combined iron and B12 deficiency may present with confusing laboratory patterns 2

Do NOT Attribute Findings to Ethnicity Without Confirmation

• Avoid attributing microcytosis to thalassemia in certain ethnic groups without laboratory confirmation via hemoglobin electrophoresis 2, 1

Management Based on Confirmed Diagnosis

If Iron Deficiency is Confirmed (Ferritin <30 μg/L or <100 μg/L with inflammation)

All adult men and post-menopausal women require comprehensive gastrointestinal evaluation:

• Perform both upper gastrointestinal endoscopy (including small bowel biopsy) and colonoscopy to exclude gastrointestinal malignancy, as asymptomatic colonic and gastric carcinoma commonly present with iron deficiency anemia 2
• Even mild anemia warrants full investigation, as severity does not correlate with likelihood of serious underlying disease 2
• Initiate oral or intravenous iron supplementation once iron deficiency is confirmed 1
• Document NSAID use, aspirin, and anticoagulants, and discontinue NSAIDs whenever possible 2

For pre-menopausal women:

• Menstrual blood loss is the most common cause, but gastrointestinal evaluation is still required if dietary history is inadequate or if anemia persists despite iron supplementation 2

If Thalassemia Trait is Confirmed

• Do not give iron supplementation unless concurrent iron deficiency is documented 1
• Provide genetic counseling if appropriate 1
• Monitor hemoglobin levels but recognize that mild anemia is expected and does not require treatment 1

If Anemia of Chronic Disease is Confirmed

• Address the underlying inflammatory or chronic condition as the primary intervention 1
• Iron supplementation is generally ineffective because the body cannot utilize stored iron in this condition 1
• Consider erythropoiesis-stimulating agents (ESAs) only in specific circumstances: In chronic kidney disease patients, use the lowest dose sufficient to reduce RBC transfusion needs, targeting hemoglobin <11 g/dL, as higher targets increase mortality, myocardial infarction, stroke, and thromboembolism risk 3

Investigation for Underlying Malignancy

This is non-negotiable for high-risk populations:

• All adult men and post-menopausal women with confirmed iron deficiency anemia require endoscopic evaluation regardless of RDW values 2, 1
• Blood loss from the gastrointestinal tract is the most common cause of iron deficiency in these populations, and asymptomatic malignancy must be excluded 2
• Common sources include colonic cancer/polyps, gastric cancer, angiodysplasia, and NSAID-related bleeding 2
• Malabsorption from coeliac disease is another important consideration requiring small bowel biopsy during upper endoscopy 2