What is the diagnosis and treatment for a patient with elevated RBC count, hemoglobin, and hematocrit, along with microcytic anemia and low MCH and MCHC levels?

Diagnostic Interpretation: Resolving Iron Deficiency with Persistent Erythrocytosis

This patient's laboratory trend demonstrates successful treatment of iron deficiency anemia (evidenced by normalization of MCV, MCH, MCHC, and RDW), but reveals an underlying polycythemia that requires immediate evaluation for polycythemia vera or secondary causes of erythrocytosis.

Key Laboratory Pattern Analysis

The serial CBC data shows a clear evolution:

• Early values (columns 1-2): Classic iron deficiency anemia with low MCV (74 fL), low MCH (23.0-22.6 pg), low MCHC (31.0-30.5 g/dL), and elevated RDW (17.5-18.3%) 1, 2
• Recent values (columns 5-7): Normalized red cell indices (MCV 85-86 fL, MCH 28.2-28.7 pg, MCHC 33.3-33.8 g/dL, RDW 13.7-14.5%) but persistently elevated RBC count (5.47-6.06 x10E6/uL), hemoglobin (15.7-17.4 g/dL), and hematocrit (46.8-51.5%) 3

Critical Diagnostic Consideration: Polycythemia Vera

The combination of microcytosis from iron deficiency masking an underlying myeloproliferative disorder is a recognized presentation of polycythemia vera (PV). 3

Immediate Next Steps

• Measure serum erythropoietin (EPO) level - This is the most practical and cost-effective next test. Low or low-normal EPO with elevated hemoglobin/hematocrit strongly suggests PV (specificity >90%) 3
• Check JAK2 V617F mutation - Present in >95% of PV cases and provides definitive molecular diagnosis 3
• Bone marrow examination with cytogenetics if EPO is low/normal or JAK2 is positive, looking for hypercellularity, megakaryocyte clustering, and pleomorphism characteristic of PV 3

Why This Matters for Morbidity and Mortality

PV carries significant thrombotic risk (the leading cause of morbidity and mortality), with major arterial and venous thromboses occurring in 12-39% of patients. The elevated hematocrit itself increases blood viscosity and thrombotic risk exponentially when >45% in men or >42% in women 3.

Alternative Diagnoses to Exclude

Secondary Polycythemia

• Hypoxic conditions: Chronic lung disease, sleep apnea, high altitude, cyanotic heart disease - these cause elevated EPO (unlike PV) 3, 4
• Renal pathology: Renal cell carcinoma, renal artery stenosis, polycystic kidney disease can cause inappropriate EPO secretion 4
• Other EPO-secreting tumors: Hepatocellular carcinoma, cerebellar hemangioblastoma 3

Relative Polycythemia (Gaisbock Syndrome)

• Elevated hemoglobin/hematocrit due to decreased plasma volume rather than true increase in red cell mass
• Consider if patient has hypertension, obesity, diuretic use, or dehydration 3

Diagnostic Algorithm

1. Confirm persistent erythrocytosis: Repeat CBC to verify hemoglobin >17.5 g/dL (men) or >15.5 g/dL (women), or hematocrit >52% (men) or >48% (women) 3

2. Measure serum EPO level:

   • Low/low-normal EPO → Proceed to JAK2 mutation testing and bone marrow examination for PV 3
   • Elevated EPO → Investigate secondary causes (pulse oximetry, arterial blood gas, chest imaging, renal ultrasound, abdominal CT) 3, 4

3. If EPO normal and clinical suspicion high: The sensitivity of low EPO for PV is only ~70%, so normal EPO does not exclude PV. Proceed with JAK2 testing and bone marrow examination 3

Treatment Implications Based on Diagnosis

If Polycythemia Vera is Confirmed

• Therapeutic phlebotomy to maintain hematocrit <45% (men) or <42% (women) to reduce thrombotic risk - this is the cornerstone of therapy 3
• Low-dose aspirin (81-100 mg daily) unless contraindicated, to reduce thrombotic events 3
• Cytoreductive therapy (hydroxyurea) if high-risk features: age >60 years or prior thrombosis 3
• Avoid iron supplementation - iron deficiency in PV is therapeutic and helps control erythrocytosis 3

If Secondary Polycythemia

• Treat underlying cause (e.g., CPAP for sleep apnea, smoking cessation, supplemental oxygen for hypoxemia) 4
• Phlebotomy may be needed if hematocrit remains >54% despite treating underlying cause 3

Critical Pitfall to Avoid

Do not dismiss the elevated RBC/hemoglobin/hematocrit as "normal variation" or "resolved anemia." The historical microcytosis with iron deficiency may have masked a significantly higher baseline erythrocytosis. Iron deficiency in PV is common due to chronic phlebotomy effect or occult bleeding, and when corrected, the true extent of erythrocytosis becomes apparent 3, 4.

The normalized MCV after iron repletion with persistent erythrocytosis is the classic presentation described in the literature as "microcytic polycythemia" that resolves to normocytic polycythemia after iron replacement 4.

Monitoring Until Diagnosis Established

• Weekly CBC until diagnostic workup complete 3
• Assess for thrombotic symptoms: Headache, visual disturbances, chest pain, erythromelalgia (burning pain in extremities), aquagenic pruritus 3
• Consider empiric low-dose aspirin if hematocrit >50% and no contraindications, given thrombotic risk while awaiting definitive diagnosis 3