What labwork is appropriate for a patient with erythrocytosis (elevated red blood cell count), hyperhemoglobinemia (elevated hemoglobin), and elevated hematocrit?

Laboratory Workup for Erythrocytosis

For a patient with RBC 5.87, hemoglobin 156 g/L, and hematocrit 0.516, order a complete blood count with red cell indices (including MCV, MCH, RDW), reticulocyte count, serum ferritin, transferrin saturation, C-reactive protein, and JAK2 mutation testing. 1

Initial Essential Laboratory Tests

The following tests should be ordered immediately to establish the diagnosis and guide management:

Core Hematologic Panel

• Complete blood count with differential and red cell indices to assess all cell lines and identify potential bone marrow disorders, as abnormalities in two or more cell lines warrant hematology consultation 2
• Reticulocyte count to evaluate bone marrow response and distinguish between increased red cell production versus other causes 2, 1
• Peripheral blood smear review to assess red cell morphology and identify abnormalities 1
• Red cell distribution width (RDW) as high RDW with normal or low MCV suggests possible coexisting iron deficiency with erythrocytosis 1

Iron Status Assessment

• Serum ferritin to evaluate tissue iron stores, as iron deficiency can coexist with erythrocytosis and cause microcytic polycythemia 2, 1
• Transferrin saturation to assess iron available for erythropoiesis, which is more reliable than ferritin alone as it is less affected by inflammation 2, 1
• C-reactive protein (CRP) to identify inflammation that affects ferritin interpretation, since ferritin acts as an acute-phase reactant 2, 1

Primary Erythrocytosis Screening

• JAK2 mutation testing (both exon 14 and exon 12) to evaluate for polycythemia vera, as JAK2 mutations are present in up to 97% of PV cases 1, 3

Secondary Testing Based on Initial Results

If JAK2 Mutation is Negative

• Erythropoietin level to differentiate primary (low EPO) from secondary (normal or elevated EPO) causes 4, 3
• Oxygen saturation measurement to assess for hypoxic causes 1
• Sleep study if nocturnal hypoxemia is suspected based on clinical history 1

If Iron Deficiency is Identified

• Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis; serum ferritin, transferrin saturation, and iron levels are required for accurate diagnosis 1
• Iron deficiency can coexist with erythrocytosis, particularly causing microcytic polycythemia with elevated RBC count but reduced hemoglobin 1

Clinical Context Considerations

Confirm True Erythrocytosis

Your patient's values (Hb 156 g/L = 15.6 g/dL, Hct 51.6%) are borderline elevated. Repeat hemoglobin and hematocrit measurements to confirm persistent elevation, as a single measurement is not reliable for establishing diagnosis 1. True erythrocytosis in men requires hemoglobin >18.5 g/dL or hematocrit >55% 1.

Assess for Secondary Causes

Obtain focused history regarding:

• Smoking status and carbon monoxide exposure, as "smoker's polycythemia" results from chronic tissue hypoxia stimulating erythropoietin production 1
• Testosterone use (prescribed or unprescribed), which can cause erythrocytosis 1
• Sleep disturbances suggesting obstructive sleep apnea, which produces nocturnal hypoxemia driving erythropoietin production 1
• Chronic lung disease or cyanotic heart disease causing hypoxia-driven erythrocytosis 1

Important Pitfalls to Avoid

• Do not use hematocrit alone for monitoring, as it can falsely increase by 2-4% with prolonged sample storage and is affected by hyperglycemia, while hemoglobin remains stable 1
• Do not perform therapeutic phlebotomy unless hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with symptoms of hyperviscosity, after excluding dehydration 1
• Do not overlook coexisting iron deficiency, as iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk 1

When to Refer to Hematology

Immediate hematology referral is indicated if:

• JAK2 mutation is positive 1
• Hemoglobin >20 g/dL with symptoms of hyperviscosity 1
• Abnormalities in two or more cell lines on CBC 2
• Unexplained splenomegaly 1
• Diagnosis remains unclear after initial workup 1