How should I evaluate and manage an adult with a hemoglobin of 19.1 g/dL?

Evaluation and Management of Hemoglobin 19.1 g/dL

A hemoglobin of 19.1 g/dL requires urgent hematology referral and systematic evaluation for polycythemia vera versus secondary causes, with therapeutic phlebotomy indicated only if symptoms of hyperviscosity develop or levels exceed 20 g/dL with hematocrit >65%. 1

Immediate Diagnostic Workup

Confirm the finding is real by repeating the complete blood count and personally reviewing the peripheral blood smear. 2 Hyperglycemia can falsely elevate calculated hematocrit, and sample storage can increase hematocrit by 2-4%. 2

Order the following laboratory tests immediately:

• Complete blood count with differential, red cell indices (MCV, MCH, MCHC), and reticulocyte count to assess bone marrow response and identify macrocytosis or other morphologic abnormalities 3
• Peripheral blood smear examination by a qualified hematologist to assess red cell morphology and identify abnormal cell lines 2
• JAK2 V617F mutation testing if hemoglobin >16.5 g/dL in women or >18.5 g/dL in men with no obvious secondary cause, as this is diagnostic for polycythemia vera 1
• Serum ferritin and transferrin saturation to rule out concurrent iron deficiency or hemochromatosis, which can coexist with erythrocytosis 3, 2
• Serum erythropoietin level (low in polycythemia vera, elevated in secondary causes) 1
• Arterial blood gas to assess for chronic hypoxemia as a secondary cause 4

Critical Differential Diagnosis

The elevated hemoglobin narrows to three primary categories:

Polycythemia Vera (Primary Erythrocytosis)

• Most important diagnosis to exclude due to thrombotic risk 2
• Diagnostic criteria include JAK2 mutation positivity, elevated hemoglobin, and bone marrow biopsy showing hypercellularity 1
• Often accompanied by thrombocytosis or leukocytosis 1
• May present with splenomegaly 1

Secondary Erythrocytosis

• Chronic hypoxemia from lung disease, sleep apnea, high altitude, or cyanotic congenital heart disease 4
• Cushing's syndrome should be routinely evaluated in unexplained polycythemia 5
• Testosterone therapy can cause erythrocytosis; if hematocrit exceeds 50%, withhold therapy until etiology investigated 3
• Renal pathology including renal cell carcinoma or renal artery stenosis 1

Relative Polycythemia (Plasma Volume Contraction)

• Dehydration, diuretic use, or chronic volume depletion 6
• In heart failure and liver disease, plasma volume expansion can mask true hemoglobin mass, but the reverse (volume contraction causing apparent erythrocytosis) also occurs 6

Urgent Referral Criteria

Refer urgently to hematology for:

• Hemoglobin >20 g/dL or hematocrit >65% (urgent referral due to thrombotic risk) 4, 1
• Any symptoms of hyperviscosity (headache, visual disturbances, poor concentration, dizziness) at any hemoglobin level 1
• Splenomegaly suggesting myeloproliferative neoplasm 1
• History of thrombotic events 1
• Abnormal blood counts in other cell lines (thrombocytosis >450,000/µL or leukocytosis >15,000/µL) 1
• Family history of polycythemia or early thrombotic events 1

Management Algorithm

If Hemoglobin 19.1 g/dL WITHOUT Symptoms:

1. Do NOT perform therapeutic phlebotomy 4, 2
2. Complete diagnostic workup as outlined above 1
3. Ensure adequate hydration 4
4. Await hematology consultation for definitive management 1

If Hemoglobin >20 g/dL or Hematocrit >65% WITH Hyperviscosity Symptoms:

1. Perform therapeutic phlebotomy of 1 unit (500 mL) with equal volume replacement using isotonic saline or dextrose 4, 2
2. The purpose is to relieve hyperviscosity symptoms, not to normalize hemoglobin 4
3. Avoid repeated routine phlebotomies as they cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increased stroke risk 4, 2

If Polycythemia Vera Confirmed:

• Target hematocrit <45% in all patients regardless of sex, as hematocrit 45-50% increases cardiovascular events 3.91-fold 3
• Initiate cytoreductive therapy if: age >60 years, previous thrombotic event, poor phlebotomy tolerance, symptomatic splenomegaly, severe symptoms, or platelet count >1,500,000/µL 3
• First-line options include hydroxyurea or recombinant interferon alpha; ruxolitinib for hydroxyurea-resistant cases 3

If Secondary Erythrocytosis from Chronic Hypoxemia:

• Patients with compensated erythrocytosis require no intervention unless hemoglobin >20 g/dL with hematocrit >65% and hyperviscosity symptoms 4
• Address underlying hypoxemia (supplemental oxygen, CPAP, treatment of lung disease) 4
• In cyanotic congenital heart disease, therapeutic phlebotomy only for hemoglobin >20 g/dL and hematocrit >65% with symptoms 4

Critical Pitfalls to Avoid

Never perform repeated routine phlebotomies without hematology guidance. This depletes iron stores, produces microcytic red cells with reduced deformability, and increases stroke risk despite lowering hemoglobin. 4, 2

Do not assume elevated hemoglobin always reflects increased red cell mass. In heart failure and liver disease, plasma volume changes can profoundly affect hemoglobin concentration independent of total hemoglobin mass. 6

Recognize that very high hemoglobin (≥17 g/dL) independently predicts increased mortality in heart failure patients (adjusted HR 1.42), so cardiac evaluation is essential. 7

Monitor for thrombotic complications closely. Hemoglobin >20 g/dL carries urgent thrombotic risk requiring immediate evaluation. 1

Check medication history carefully. Testosterone therapy, hydroxyurea, and other medications can cause erythrocytosis and must be identified. 3, 2