What does low hemoglobin (Hb) and hematocrit (Hct) with normochromic normocytic anemia and high Red Cell Distribution Width Standard Deviation (RDW-SD) indicate?

Normochromic Normocytic Anemia with Low Hemoglobin, Low Hematocrit, and High RDW-SD: Diagnostic Implications

Low hemoglobin and hematocrit with normochromic normocytic anemia and high RDW-SD most likely indicates anemia of chronic disease, potentially with early iron deficiency or mixed etiology requiring further diagnostic workup to determine the underlying cause.

Understanding the Laboratory Parameters

• Normochromic normocytic anemia (normal MCV and normal MCHC) with elevated RDW-SD indicates increased variation in red blood cell size (anisocytosis) despite normal average cell size 1
• High RDW-SD (Red Cell Distribution Width-Standard Deviation) reflects greater heterogeneity in red cell population, suggesting an underlying pathological process affecting red cell production or survival 1, 2
• Low hemoglobin and hematocrit confirm the presence of anemia, with normal values for adult males being 15.5 ± 2.0 g/dL and 47 ± 6% respectively, and for adult females 14.0 ± 2.0 g/dL and 41 ± 5% respectively 1

Most Common Diagnostic Possibilities

1. Anemia of Chronic Disease (ACD)

• Normochromic and normocytic presentation is characteristic of anemia of chronic kidney disease and other chronic inflammatory conditions 1
• Elevated RDW can occur in ACD, particularly when there is concurrent iron-restricted erythropoiesis 1
• Often seen in patients with chronic kidney disease, chronic inflammation, malignancy, or chronic infections 1

2. Early or Developing Iron Deficiency

• Iron deficiency typically presents as microcytic anemia, but in early stages may be normocytic with elevated RDW 1, 3
• RDW often increases before MCV decreases, making it an early indicator of developing iron deficiency 1, 3
• The sensitivity of RDW-CV for diagnosing iron deficiency anemia is approximately 77.1% 3

3. Mixed Nutritional Deficiency

• Combined deficiencies (e.g., iron deficiency with folate or B12 deficiency) can present as normocytic anemia with elevated RDW 1
• Macrocytosis from B12/folate deficiency may be masked by concurrent microcytosis from iron deficiency, resulting in a normal MCV but high RDW 1, 4

Recommended Diagnostic Approach

1. Assess iron status:

   • Measure serum ferritin (reflects total body iron stores) 1
   • Check transferrin saturation (TSAT) (reflects iron immediately available for hemoglobin synthesis) 1
   • Consider measuring percentage of hypochromic red blood cells if available 1

2. Evaluate for chronic disease:

   • Check inflammatory markers (CRP, ESR) 1
   • Assess kidney function (eGFR, creatinine) as anemia prevalence increases with declining kidney function 1
   • Screen for diabetes, which is associated with earlier onset of anemia at higher GFR levels 1

3. Rule out other nutritional deficiencies:

   • Measure vitamin B12 and folate levels 1
   • Check reticulocyte count to assess bone marrow response 1

4. Consider additional testing based on clinical suspicion:

   • Hemolysis workup (haptoglobin, LDH, bilirubin) if hemolysis is suspected 1
   • Stool guaiac test for occult gastrointestinal bleeding if iron deficiency is confirmed 1
   • Hemoglobin electrophoresis if hemoglobinopathy is suspected 1, 5

Clinical Pitfalls to Avoid

• Don't assume normocytic anemia excludes iron deficiency: Early iron deficiency can present with normal MCV but elevated RDW 1, 3
• Don't rely solely on RDW for diagnosis: While elevated RDW is sensitive for detecting abnormal red cell populations, it lacks specificity for particular conditions 6, 5
• Don't overlook mixed deficiencies: Concurrent deficiencies can result in normocytic indices despite significant underlying abnormalities 1, 4
• Don't forget to consider chronic kidney disease: Anemia of CKD is typically normocytic and normochromic and becomes more prevalent as GFR declines below 60 mL/min/1.73m² 1
• Don't ignore diabetes as a risk factor: Patients with diabetes develop anemia at earlier stages of CKD and have higher prevalence of anemia at all GFR levels 1

Treatment Considerations

• Treatment should target the underlying cause rather than just the anemia 1
• If iron deficiency is confirmed, investigate for potential sources of blood loss, particularly gastrointestinal bleeding in adults 1
• For anemia of chronic disease, addressing the underlying condition is the primary approach 1
• Regular monitoring of hemoglobin is recommended over hematocrit due to greater accuracy and less variability in measurement 1