What is the management approach for a patient with elevated Red Blood Cell (RBC) count and Hematocrit (H&H) levels?

Management of Elevated RBC Count, Hemoglobin, and Hematocrit

The first priority is to confirm true erythrocytosis by ensuring adequate hydration status and repeating measurements, then systematically evaluate for secondary causes before considering primary polycythemia vera, with therapeutic phlebotomy reserved only for extreme elevations (hemoglobin >20 g/dL and hematocrit >65%) with hyperviscosity symptoms. 1

Initial Confirmation and Assessment

• Repeat hemoglobin and hematocrit measurements after ensuring adequate hydration, as a single measurement is insufficient for diagnosis and dehydration can cause relative erythrocytosis 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 2
• Assess for hyperviscosity symptoms including headache, visual disturbances, fatigue, poor concentration, or dizziness 1
• Evaluate for cardiopulmonary symptoms suggesting chronic hypoxemia as a secondary cause 1

Essential Laboratory Workup

Order the following tests immediately to distinguish primary from secondary erythrocytosis: 2

• Complete blood count with red cell indices, reticulocyte count, and differential to assess white blood cell and platelet counts 2
• Serum ferritin and transferrin saturation to evaluate iron status, as iron deficiency can mask the full extent of erythrocytosis while 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 2
• Serum erythropoietin (EPO) level: low or low-normal suggests polycythemia vera, while elevated levels indicate secondary erythrocytosis 1, 3

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

Evaluation for Secondary Causes

Before pursuing polycythemia vera workup, systematically exclude these common secondary causes:

• Smoking history and carbon monoxide exposure, which causes "smoker's polycythemia" through chronic tissue hypoxia stimulating erythropoietin production 1, 2
• Obstructive sleep apnea through sleep study if nocturnal hypoxemia is suspected 1, 2
• Chronic lung disease including COPD through pulmonary function testing and arterial oxygen saturation measurement 2, 4
• Testosterone use (prescribed or unprescribed), which commonly causes erythrocytosis in younger adults 2
• Cyanotic congenital heart disease with right-to-left shunting causing compensatory erythrocytosis 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 1

Testing for Polycythemia Vera

If secondary causes are excluded and EPO is low or low-normal, proceed with JAK2 mutation testing: 2, 3

• Test for JAK2 V617F mutation (present in >95% of polycythemia vera cases) and JAK2 exon 12 mutations 2, 3
• World Health Organization diagnostic criteria require either:
  • Both major criteria (elevated hemoglobin/hematocrit AND JAK2 mutation) plus one minor criterion, OR
  • First major criterion plus two minor criteria 2
• Minor criteria include bone marrow hypercellularity, low serum EPO, or endogenous erythroid colony growth 2

Management Approach

For Secondary Erythrocytosis

Treat the underlying condition rather than performing phlebotomy: 1, 2

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

For Polycythemia Vera (JAK2 Positive)

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk, 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, 3
• Refer immediately to hematology for definitive management 2, 3

Therapeutic Phlebotomy Indications

Phlebotomy is indicated ONLY in these specific circumstances: 1, 2

• 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

Iron Management

Avoid routine phlebotomies as they cause iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1, 2

• Iron deficiency should be corrected even in the presence of erythrocytosis, as iron-deficient red cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk 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
• Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis; use serum ferritin, transferrin saturation, and iron levels 1

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 use hemoglobin level alone as a transfusion or phlebotomy trigger; consider intravascular volume status, evidence of shock, and cardiopulmonary parameters 5
• Do not overlook coexisting iron deficiency, which can mask the full extent of erythrocytosis while still contributing to hyperviscosity symptoms 1
• Do not apply standard polycythemia vera diagnostic thresholds at high altitude without adjustment for physiologic adaptation 1
• Do not assume anemia is normal with aging when evaluating baseline hemoglobin values 1

Hematology Referral Indications

Refer immediately to hematology if: 2, 3

• JAK2 mutation is positive 2, 3
• Hemoglobin >20 g/dL with symptoms of hyperviscosity 2
• Unexplained splenomegaly 2
• Diagnosis remains unclear after initial workup 1, 3
• Elevated thrombocyte or leukocyte count suggesting myeloproliferative disorder 3, 4