What is the appropriate management for an adult patient with elevated hemoglobin and hematocrit levels, and a ferritin level of 25 ng/mL, with no significant medical history?

Management of Elevated Hemoglobin and Hematocrit with Low Ferritin

This patient requires immediate investigation for the underlying cause of erythrocytosis before any intervention, with iron supplementation as the priority given the low ferritin of 25 ng/mL, which indicates iron deficiency that must be corrected to prevent stroke and other vascular complications. 1

Immediate Diagnostic Workup

Order the following tests to differentiate polycythemia vera from secondary erythrocytosis:

• JAK2 V617F mutation testing - present in approximately 98% of polycythemia vera cases 2, 3, 4
• Serum erythropoietin level - subnormal in polycythemia vera, elevated in secondary causes 2, 4
• Oxygen saturation - to evaluate for hypoxemia-driven secondary erythrocytosis 1
• Complete metabolic panel - assess renal function as cyanotic patients develop glomerular abnormalities 1
• Peripheral blood smear - evaluate red cell morphology and confirm iron deficiency 1
• Transferrin saturation - values <20% confirm functional iron deficiency 2

Critical Management Based on Ferritin Level

The ferritin of 25 ng/mL represents iron deficiency that is dangerous in the setting of erythrocytosis. Iron-deficient red blood cells have reduced oxygen-carrying capacity and decreased deformability, which paradoxically increases stroke risk and vascular complications despite the elevated hemoglobin 1, 2.

Iron Repletion Protocol

• Initiate oral iron supplementation immediately with close hemoglobin monitoring, as iron administration can cause rapid increases in red cell mass 1
• Continue supplementation until ferritin reaches normal range and transferrin saturation exceeds 20% 1, 2
• If oral iron is not tolerated, use pulsed intravenous iron supplementation 1
• Monitor hemoglobin weekly during iron repletion to detect rapid rises 1

Phlebotomy Decision Algorithm

Do NOT perform phlebotomy at this time given the iron deficiency. 1

Phlebotomy is ONLY indicated if ALL of the following criteria are met:

1. Hemoglobin >20 g/dL AND hematocrit >65% (current values of 17.5 g/dL and 53.2% do not meet this threshold) 1, 2
2. Symptoms of hyperviscosity present - headache, poor concentration, fatigue, dizziness, blurred vision, or tinnitus 1, 5
3. Patient is adequately hydrated - dehydration must be excluded first 1
4. Iron stores are replete - ferritin normal and transferrin saturation >20% 1, 2

The current hematocrit of 53.2% is below the 65% threshold where hyperviscosity symptoms typically occur in iron-replete patients. 2, 5 Repeated routine phlebotomies are contraindicated as they cause iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1.

If Polycythemia Vera is Diagnosed

Target hematocrit strictly below 45% through therapeutic phlebotomy to reduce cardiovascular death and major thrombotic events from 9.8% to 2.7%. 2

Phlebotomy Protocol for Polycythemia Vera:

• Induction phase: Remove 300-450 mL weekly or twice weekly until hematocrit <45% 2
• Maintenance phase: Same volume per session with intervals determined by hematocrit monitoring 2
• Add low-dose aspirin 100 mg daily unless contraindicated 2, 4

Cytoreductive Therapy Indications:

Mandatory if ANY of the following:

• Age ≥60 years 2
• History of prior thrombosis 2
• Poor phlebotomy tolerance 2
• Symptomatic or progressive splenomegaly 2
• Platelet count >1,500 × 10⁹/L 2
• Leukocyte count >15 × 10⁹/L 2

First-line agent: Hydroxyurea 2, 3, 4

If Secondary Erythrocytosis is Diagnosed

Identify and treat the underlying cause - chronic lung disease, sleep apnea, congenital heart disease, smoking, testosterone use 1, 4

• Hydration is first-line therapy for any suspected hyperviscosity symptoms - administer oral fluids or IV normal saline before considering phlebotomy 2
• Routine phlebotomy is contraindicated in secondary erythrocytosis as it depletes iron stores and worsens outcomes 1
• The patient's homeostatic processes generally achieve optimal red cell mass without intervention 2

Common Pitfalls to Avoid

• Never perform phlebotomy in the presence of iron deficiency - this is the most common and dangerous error, as it further compromises oxygen delivery and increases stroke risk 1, 2
• Do not assume symptoms are from hyperviscosity when hematocrit is <65% - iron deficiency itself can cause fatigue, headache, and poor concentration that mimic hyperviscosity 2, 5
• Avoid aggressive phlebotomy in secondary erythrocytosis - this is the most likely cause of complications, not the elevated hematocrit itself 1
• Always hydrate before considering phlebotomy - dehydration can falsely elevate hematocrit and cause symptoms 1, 2

Monitoring Plan

• Recheck complete blood count in 2-4 weeks after initiating iron supplementation 2
• Monitor ferritin and transferrin saturation until iron stores are replete 1, 2
• Once diagnosis is established, follow disease-specific monitoring protocols 2