What is the management and evaluation plan for a patient with a high red blood cell (RBC) count, low mean corpuscular hemoglobin (MCH), and low mean corpuscular hemoglobin concentration (MCHC)?

Evaluation and Management of High RBC Count with Low MCH and Low MCHC

Primary Diagnostic Consideration

This pattern of high RBC count with low MCH and low MCHC most strongly suggests thalassemia minor (alpha or beta thalassemia trait), which should be your leading diagnosis. 1

Initial Diagnostic Workup

Obtain the following laboratory tests immediately to establish the diagnosis:

• Complete iron studies including serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity to definitively exclude or confirm iron deficiency 2, 3
• Hemoglobin electrophoresis to identify thalassemia trait or other hemoglobinopathies, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 2, 3
• Absolute reticulocyte count to assess bone marrow response and rule out hemolysis 2, 3
• Red blood cell distribution width (RDW) if not already available, as RBC size distribution curves reliably distinguish between thalassemia minor and polycythemia with iron deficiency 1

Differential Diagnosis Algorithm

If Iron Studies Show Iron Deficiency (Ferritin <30 μg/L or TSAT <15-16%):

This represents polycythemia with concurrent iron deficiency 1:

• Investigate for secondary polycythemia causes including chronic hypoxia (COPD, sleep apnea, high altitude residence, smoking), renal pathology (hypernephroma, renal artery stenosis), or other causes of increased erythropoietin production 1
• After iron repletion, the RBC count will remain elevated but MCV and MCH should normalize if this is the correct diagnosis 1
• Consider polycythemia vera if the patient also has elevated white blood cell count or platelet count, splenomegaly, or other concerning features 1

If Iron Studies Are Normal:

Thalassemia minor is the most likely diagnosis 1:

• Hemoglobin electrophoresis will confirm beta-thalassemia trait by showing elevated HbA2 (>3.5%) 2
• Alpha-thalassemia trait may show normal hemoglobin electrophoresis and requires genetic testing for definitive diagnosis 2
• RBC size distribution curves in thalassemia show a narrow, uniform distribution unlike the wide distribution seen in iron deficiency 1

Key Distinguishing Features

MCH is a more reliable marker than MCHC because it is less dependent on storage conditions and counting machine variability 2:

• In thalassemia trait: RBC count typically >5.5 million/μL, MCV 60-75 fL, MCH <27 pg, normal RDW 1
• In polycythemia with iron deficiency: RBC count elevated but variable, progressive microcytosis, elevated RDW, low ferritin or TSAT 1

Clinical Pitfalls to Avoid

Do not accept ferritin alone in patients with inflammation, chronic disease, or malignancy as ferritin can be falsely elevated; use TSAT to confirm iron status in these situations 2, 3

Do not assume dietary iron deficiency without full investigation in adult men and postmenopausal women, as gastrointestinal bleeding or malignancy must be excluded 2, 3

Do not overlook the ethnic background when considering hemoglobinopathies, as thalassemia trait is significantly more common in specific populations 2, 3

Management Based on Final Diagnosis

If Thalassemia Trait Confirmed:

• No treatment is required as this is a benign condition 1
• Provide genetic counseling if the patient is of reproductive age 2
• Avoid unnecessary iron supplementation which can lead to iron overload 2

If Polycythemia with Iron Deficiency Confirmed:

• Treat the iron deficiency with oral or intravenous iron as appropriate 2
• Investigate and treat the underlying cause of both the polycythemia and the iron deficiency 1
• Monitor response to iron therapy: MCV and MCH should normalize while RBC count remains elevated 1