How to manage a patient with polycythemia indicated by elevated hemoglobin and RBC count?

Management of Elevated Hemoglobin and RBC Count

This patient's hemoglobin of 170 g/L (17.0 g/dL) and RBC of 5.61 × 10¹²/L represents borderline erythrocytosis that requires confirmation with repeat testing after ensuring adequate hydration, followed by systematic evaluation for secondary causes before considering polycythemia vera. 1, 2

Initial Confirmation and Assessment

Repeat measurements are essential because a single elevated value is insufficient for diagnosis and may reflect relative polycythemia from dehydration or plasma volume contraction. 1, 2

• Confirm true erythrocytosis using sex-specific thresholds: hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, and hematocrit >55% in men or >49.5% in women 1
• This patient's hemoglobin of 17.0 g/dL falls below the diagnostic threshold for men (18.5 g/dL) but warrants investigation given the elevated RBC count 1
• Ensure adequate hydration status before repeating measurements, as dehydration commonly causes spurious elevation 2, 3

Assess for hyperviscosity symptoms including headache, visual disturbances, fatigue, poor concentration, dizziness, or unusual thrombosis 1, 2

Essential Laboratory Workup

Order the following tests immediately to distinguish primary from secondary erythrocytosis:

• Complete blood count with red cell indices, reticulocyte count, and differential to assess white blood cell and platelet counts (thrombocytosis or leukocytosis suggests myeloproliferative disorder) 1, 2
• Serum ferritin and transferrin saturation to evaluate iron status, as iron deficiency can mask the full extent of erythrocytosis while paradoxically increasing stroke risk 1, 2
• Peripheral blood smear to evaluate red cell morphology and identify abnormalities 1, 2
• Red cell distribution width (RDW), as high RDW with normal or low MCV suggests coexisting iron deficiency 1
• Serum erythropoietin (EPO) level: low or low-normal suggests polycythemia vera, while elevated levels indicate secondary erythrocytosis 1, 2, 4

Hemoglobin is more reliable than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage and is affected by hyperglycemia, while hemoglobin remains stable. 1

Systematic Evaluation for Secondary Causes

Before considering polycythemia vera, systematically exclude secondary causes:

• Smoking history and carbon monoxide exposure, which causes "smoker's polycythemia" through chronic tissue hypoxia stimulating erythropoietin production (resolves with smoking cessation) 1, 2
• Obstructive sleep apnea through sleep study if nocturnal hypoxemia is suspected, as this produces nocturnal hypoxemia driving erythropoietin production 1, 2
• Chronic lung disease including COPD through pulmonary function testing and arterial oxygen saturation measurement 1, 2
• Testosterone use (prescribed or unprescribed), which commonly causes erythrocytosis in younger adults and requires dose adjustment or discontinuation 1, 2
• Altitude of residence, as physiologic adaptation increases hemoglobin by 0.2-4.5 g/dL depending on elevation (1000-4500 meters) 1
• Erythropoietin-producing tumors including renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma through renal imaging (ultrasound or CT) 1, 2
• Cyanotic congenital heart disease with right-to-left shunting causing compensatory erythrocytosis 1, 2

Testing for Polycythemia Vera

If secondary causes are excluded or EPO levels are low/normal:

• Test for JAK2 mutations (both exon 14 V617F and exon 12), which are present in up to 97% of polycythemia vera cases 1, 4
• Polycythemia vera diagnosis requires both major criteria (elevated hemoglobin/hematocrit/RBC mass AND presence of JAK2 mutation) plus at least one minor criterion, OR first major criterion plus at least two minor criteria 1
• Minor criteria include bone marrow hypercellularity with trilineage growth, subnormal serum erythropoietin level, and endogenous erythroid colony formation 1
• Bone marrow biopsy is required if JAK2 mutation is positive to confirm diagnosis and assess for trilineage myeloproliferation 1

A critical caveat: Rare cases of "masked" polycythemia vera can present with normal hemoglobin and hematocrit due to blood dilution or coincidental blood loss, but still carry JAK2 mutations and thrombotic risk. 5

Management Based on Etiology

For Secondary Erythrocytosis:

Treat the underlying condition rather than performing phlebotomy:

• Smoking cessation for smoker's polycythemia 1, 2
• CPAP therapy for obstructive sleep apnea 1, 2
• Management of chronic lung disease 1, 2
• Dose adjustment or discontinuation of testosterone if causative 1, 2
• Monitor hemoglobin and hematocrit periodically 2

In secondary erythrocytosis, the elevated hematocrit serves a compensatory physiological role to optimize oxygen transport, and the body naturally regulates red cell mass to an optimal level. 1

For Confirmed Polycythemia Vera:

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk (CYTO-PV trial showed 2.7% vs 9.8% thrombotic event rate, P=0.007), with a lower target of 42% reasonable for women and African Americans. 1, 2

Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention. 1, 2

Therapeutic Phlebotomy: Strict Indications Only

Phlebotomy is indicated ONLY in these specific circumstances:

• Hemoglobin >20 g/dL AND hematocrit >65% with symptoms of hyperviscosity, after excluding dehydration 1, 2
• Confirmed polycythemia vera requiring hematocrit maintenance <45% 1, 2

When performing phlebotomy, replace with equal volume of dextrose or saline to prevent further hemoconcentration. 1

Repeated routine phlebotomies are explicitly contraindicated in secondary polycythemia because they cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 1, 2

Iron Management

Iron deficiency should be corrected even in the presence of erythrocytosis because iron-deficient red cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk. 1, 2

• If transferrin saturation <20%, treat with iron supplementation rather than phlebotomy 1
• If iron deficiency is confirmed, provide cautious oral iron supplementation with close hemoglobin monitoring, as rapid increases in red cell mass can occur 1, 2
• Iron deficiency causes symptoms identical to hyperviscosity but requires the opposite treatment 1

Hematology Referral Indications

Refer immediately to hematology if:

• JAK2 mutation is positive 1, 2
• Hemoglobin >20 g/dL with symptoms of hyperviscosity 1, 2
• Unexplained splenomegaly 1, 2
• Diagnosis remains unclear after initial workup 1, 2
• Elevated thrombocyte or leukocyte count suggesting myeloproliferative disorder 1, 2

Critical Pitfalls to Avoid

Never perform aggressive or repeated routine phlebotomies without specific indications, as this depletes iron stores and paradoxically increases thrombotic risk. 1, 2

Do not overlook coexisting iron deficiency, which can mask the full extent of erythrocytosis while still contributing to hyperviscosity symptoms and stroke risk. 1, 2

Do not apply standard polycythemia vera diagnostic thresholds at high altitude without adjustment for physiologic adaptation (0.2-4.5 g/dL increase depending on elevation). 1

Do not use hemoglobin level alone as a phlebotomy trigger; consider intravascular volume status, evidence of hyperviscosity symptoms, and cardiopulmonary parameters. 2