What does it mean to have elevated Hemoglobin (Hb), Mean Corpuscular Volume (MCV), and Mean Corpuscular Hemoglobin (MCH) levels?

Elevated Hemoglobin, MCV, and MCH: Macrocytic Polycythemia

Elevated hemoglobin with elevated MCV and MCH indicates macrocytic polycythemia, most commonly caused by chronic hypoxia with compensatory erythrocytosis, polycythemia vera, or secondary polycythemia from other causes. 1, 2

Understanding the Pattern

This combination represents larger-than-normal red blood cells (macrocytosis) with increased total hemoglobin, which is distinctly different from macrocytic anemia where hemoglobin would be low. 2

Key Differential Diagnoses

Primary considerations include:

• Chronic hypoxia (COPD, high altitude, chronic lung disease) causing compensatory increased red cell production with larger cells 3
• Polycythemia vera - a myeloproliferative disorder causing uncontrolled red cell production 3
• Secondary polycythemia from renal tumors (hypernephroma), hepatocellular carcinoma, or other erythropoietin-secreting tumors 3
• Smoking-related polycythemia with carboxyhemoglobin elevation 4

Less common causes:

• Hypothyroidism can cause both elevated MCV and sometimes mild polycythemia 2, 4
• Liver disease may elevate MCV while occasionally causing polycythemia 4
• Alcohol excess elevates MCV but typically doesn't cause true polycythemia 4

Essential Diagnostic Workup

Immediate laboratory tests needed:

• Reticulocyte count - elevated in active erythropoiesis from hypoxia or polycythemia vera 5
• Serum erythropoietin level - low/normal in polycythemia vera, elevated in secondary causes 3
• Oxygen saturation and arterial blood gas - identifies hypoxic drive 3
• JAK2 mutation testing - positive in >95% of polycythemia vera cases 3
• Vitamin B12 and folate levels - to exclude megaloblastic causes masking as polycythemia 2, 4
• Thyroid function tests (TSH) - hypothyroidism can cause macrocytosis 2
• Liver function tests - hepatic disease affects MCV 4

Clinical assessment priorities:

• Smoking history and carboxyhemoglobin level - smoking is a common reversible cause 3
• Respiratory symptoms - chronic hypoxia from lung disease 3
• Sleep patterns - obstructive sleep apnea causes intermittent hypoxia 3
• Medication review - testosterone, anabolic steroids, erythropoietin 3
• Symptoms of hyperviscosity - headache, dizziness, visual disturbances, pruritus after bathing (classic for polycythemia vera) 3

Critical Pitfalls to Avoid

Do not assume vitamin B12/folate deficiency - while these cause macrocytosis, they cause anemia (low hemoglobin), not polycythemia. The elevated hemoglobin excludes typical megaloblastic anemia. 2, 4

Do not overlook secondary causes - approximately 15% of cases with this pattern have secondary polycythemia from hypoxia with incidental causes of macrocytosis, not polycythemia vera. 3

Recognize that iron deficiency can coexist - if a patient with polycythemia vera develops iron deficiency, the MCV may normalize or become low, masking the underlying disorder. 3

Management Algorithm

Step 1: Confirm true polycythemia

• Verify hemoglobin elevation on repeat testing 1
• Exclude relative polycythemia (dehydration, diuretics) 3

Step 2: Determine primary vs. secondary

• If erythropoietin low/normal + JAK2 positive → Polycythemia vera, refer to hematology 3
• If erythropoietin elevated → Investigate hypoxic causes (pulmonary function tests, sleep study, imaging for tumors) 3

Step 3: Address macrocytosis

• If reticulocyte count elevated → Active erythropoiesis explains macrocytosis 4
• If reticulocyte count normal/low → Investigate thyroid, liver, alcohol, medications 2, 4

Step 4: Risk stratification

• Assess thrombotic risk from hyperviscosity 3
• Consider phlebotomy if hematocrit >45% in polycythemia vera or symptomatic hyperviscosity 3