What is the management for elevated hemoglobin and hematocrit levels?

Management of Elevated Hemoglobin and Hematocrit

The first critical step is to identify whether this represents polycythemia vera (requiring JAK2 mutation testing) or secondary erythrocytosis, as management differs fundamentally between these conditions—with polycythemia vera requiring strict hematocrit control below 45% through phlebotomy and aspirin, while secondary erythrocytosis demands treatment of the underlying cause and avoidance of routine phlebotomy. 1

Diagnostic Workup

Initial Laboratory Evaluation

• Order complete blood count with red cell indices, reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and C-reactive protein 2
• Confirm true erythrocytosis by documenting hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, or hematocrit >55% in men or >49.5% in women on repeated measurements 2
• Test for JAK2 mutations (both exon 14 and exon 12) to differentiate polycythemia vera from secondary causes 1, 2
• Measure erythropoietin levels—low or normal EPO suggests polycythemia vera, while elevated EPO indicates secondary erythrocytosis 2

Evaluate for Secondary Causes

• Assess for hypoxic causes: obstructive sleep apnea (order sleep study if nocturnal hypoxemia suspected), chronic obstructive pulmonary disease, cyanotic congenital heart disease, and smoking history 2
• Screen for non-hypoxic causes: testosterone use (prescribed or unprescribed), erythropoietin-producing tumors (renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma), and chronic carbon monoxide exposure 2
• High RDW with normal or low MCV suggests coexisting iron deficiency, which requires specific evaluation 2

Management of Polycythemia Vera

Hematocrit Control Through Phlebotomy

• Maintain hematocrit strictly below 45% through therapeutic phlebotomy—this reduces cardiovascular death and major thrombotic events from 9.8% to 2.7% (HR 3.91). 1
• Induction phase: Remove 300-450 mL weekly or twice weekly until hematocrit <45% 1
• Maintenance phase: Continue same volume per session with intervals determined by hematocrit monitoring 1
• Monitor complete blood count every 2-4 weeks during induction, then every 3 months 1

Antiplatelet Therapy

• Prescribe low-dose aspirin 100 mg daily for all polycythemia vera patients unless contraindicated to significantly reduce thrombotic events 1

Cytoreductive Therapy Indications

• Initiate cytoreductive therapy if any of the following are present: age ≥60 years, history of prior thrombosis, poor phlebotomy tolerance, symptomatic or progressive splenomegaly, platelet count >1,500 × 10⁹/L, or leukocyte count >15 × 10⁹/L 1
• First-line agents: hydroxyurea (most commonly used) or interferon alfa/pegylated interferon (particularly effective for younger patients and those with intractable pruritus) 1
• Consider ruxolitinib for patients who fail first-line therapy—clinical practice data show 88% achieve hematocrit control by three months with low thrombotic risk 1, 3

Management of Secondary Erythrocytosis

Critical Principle: Avoid Routine Phlebotomy

• Do not perform routine phlebotomy in secondary erythrocytosis—it causes iron deficiency, decreases oxygen-carrying capacity, and paradoxically increases stroke risk. 1, 4
• Phlebotomy is indicated ONLY when all of the following criteria are met: hemoglobin >20 g/dL AND hematocrit >65%, symptoms of hyperviscosity are present (headache, poor concentration), patient is adequately hydrated, and no iron deficiency exists 1
• When phlebotomy is performed, replace with equal volume of dextrose or saline to prevent further hemoconcentration 1

Treat the Underlying Cause

• Smoking cessation for smoker's polycythemia (carbon monoxide-induced erythrocytosis) 1, 2
• CPAP therapy for obstructive sleep apnea 1, 2
• Management of chronic lung disease 1
• Testosterone dose adjustment or temporary discontinuation if causative 2
• Surgical resection of erythropoietin-producing tumors when feasible 2

Hydration as First-Line Therapy

• Administer oral fluids or intravenous normal saline as first-line therapy for suspected hyperviscosity symptoms—NOT phlebotomy 1
• Only consider phlebotomy if symptoms persist despite adequate hydration and hematocrit remains significantly elevated above patient's baseline 1

Iron Management Across All Causes

Critical Consideration

• Iron deficiency should be evaluated and treated before considering phlebotomy, as iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke and myocardial ischemia risk. 1
• Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis—use serum ferritin, transferrin saturation, and iron levels 2
• If transferrin saturation <20%, treat with cautious oral iron supplementation until stores are replete, monitoring hemoglobin closely as rapid increases in red cell mass can occur 1

Common Pitfalls to Avoid

• Performing routine phlebotomy in secondary erythrocytosis without clear indications leads to iron deficiency and compromises oxygen transport, potentially worsening outcomes. 1
• Overlooking iron deficiency, which can mimic hyperviscosity symptoms 1
• Using a single hemoglobin or hematocrit measurement to make treatment decisions—always confirm with repeated measurements 2
• Failing to test for JAK2 mutations, which are present in up to 97% of polycythemia vera cases and fundamentally change management 2
• Allowing rapid increases in hematocrit (>8 percentage points per month) in patients on erythropoietin therapy—reduce dose by 25% if this occurs 2

Monitoring and Follow-Up

• For polycythemia vera: Monitor CBC every 2-4 weeks during induction, then every 3 months; assess response using European LeukemiaNet criteria; evaluate for disease progression and transformation 1
• For secondary erythrocytosis: Monitor hematocrit every 3-6 months, assess iron status regularly, and evaluate for progression of underlying disease 1
• For all patients on cytoreductive therapy: Monitor for potential side effects and treatment response 1