What is the workup for a patient with elevated Red Blood Cell (RBC) count and low Mean Corpuscular Hemoglobin Concentration (MCHC)?

Workup for Elevated RBC Count and Low MCHC

The workup for a patient with elevated RBC count and low MCHC should include a comprehensive hematologic evaluation focusing on iron deficiency, thalassemia traits, and other causes of microcytic hypochromic anemia as the most likely diagnoses. 1

Initial Laboratory Evaluation

Essential Tests:

• Complete blood count (CBC) with RBC indices
• Peripheral blood smear examination
• Serum ferritin
• Transferrin saturation (TfS)
• C-reactive protein (CRP)
• Reticulocyte count
• Direct and indirect bilirubin

Additional Tests Based on Initial Results:

• Iron studies:
  • Total iron binding capacity
  • Serum iron
• Hemoglobin electrophoresis (to evaluate for thalassemia)
• Glucose-6-phosphate dehydrogenase level
• Vitamin B12 and folate levels
• Liver function tests

Interpretation of Findings

Pattern Recognition:

• Elevated RBC + Low MCHC + Low MCV: Strongly suggests iron deficiency anemia or thalassemia trait 1, 2
• Elevated RBC + Low MCHC + Normal MCV: Consider early iron deficiency or combined nutritional deficiencies
• Elevated RBC + Low MCHC + High RDW: More consistent with iron deficiency 1, 2
• Elevated RBC + Low MCHC + Normal RDW: More consistent with thalassemia trait 2

Differential Diagnosis:

1. Iron Deficiency Anemia:

   • Low ferritin (<30 μg/L without inflammation, <100 μg/L with inflammation)
   • Low transferrin saturation (<20%)
   • Elevated RDW
   • Microcytic hypochromic cells on peripheral smear 1

2. Thalassemia Trait:

   • Normal or elevated ferritin
   • Normal or slightly decreased transferrin saturation
   • Normal RDW
   • Target cells on peripheral smear
   • Family history may be positive 2

3. Hemochromatosis (early stage):

   • Elevated transferrin saturation (>45%)
   • Elevated ferritin
   • May have increased RBC count with altered MCV, MCH, and MCHC 3

4. Sickle Cell Disease/Trait:

   • Abnormal hemoglobin electrophoresis
   • Sickle cells on peripheral smear 4

5. Anemia of Chronic Disease:

   • Elevated ferritin (>100 μg/L)
   • Low transferrin saturation (<20%)
   • Evidence of underlying inflammatory condition 1

Further Workup Based on Initial Findings

If Iron Deficiency is Suspected:

• Evaluate for sources of blood loss:
  • Gastrointestinal evaluation (endoscopy)
  • Gynecological evaluation in women of reproductive age
  • Urinalysis to check for hematuria

If Thalassemia is Suspected:

• Hemoglobin electrophoresis
• Genetic testing
• Family screening

If Hemochromatosis is Suspected:

• HFE gene mutation analysis
• Liver function tests
• Consider liver biopsy if advanced disease is suspected 3

Common Pitfalls to Avoid

1. False elevation of MCHC: Can occur due to cold agglutinins, lipemia, or hemolysis. If MCHC is unusually high, consider repeating the test after warming the sample to 37°C 5

2. Missing combined deficiencies: Iron deficiency can coexist with other nutritional deficiencies (B12, folate) or with thalassemia trait, creating mixed pictures 1

3. Relying solely on MCV: The combination of RBC count, MCHC, MCV, and RDW provides better diagnostic accuracy than any single parameter 2

4. Overlooking inflammation: Acute or chronic inflammation can mask iron deficiency by elevating ferritin levels 1

5. Premature diagnosis: Avoid diagnosing iron deficiency based solely on low MCHC without confirming with ferritin and transferrin saturation 1

By following this systematic approach to evaluating elevated RBC count with low MCHC, clinicians can efficiently identify the underlying cause and initiate appropriate management to improve patient outcomes.