What is erythrocytosis?

Erythrocytosis Definition

Erythrocytosis is defined as an elevation of hemoglobin above 16.5 g/dL in men and above 16 g/dL in women, with hematocrit levels exceeding 49% in men and 48% in women. 1

Classification of Erythrocytosis

Erythrocytosis can be classified into several categories based on underlying mechanisms:

Primary vs. Secondary Erythrocytosis

• Primary Erythrocytosis: Results from intrinsic abnormalities in the myeloid compartment of bone marrow, leading to increased red cell production 1
• Secondary Erythrocytosis: Occurs due to external stimuli to the bone marrow causing excessive red cell production; more common than primary erythrocytosis 1, 2
• Idiopathic Erythrocytosis: Cases where neither primary nor secondary causes can be established 2, 3

Absolute vs. Apparent Erythrocytosis

• Absolute Erythrocytosis: Confirmed by measured red cell mass above the reference range for an individual's height and weight 2
• Apparent Erythrocytosis: Elevated hematocrit without true increase in red cell mass, often due to decreased plasma volume (e.g., dehydration) 2

Congenital vs. Acquired Erythrocytosis

Both primary and secondary erythrocytosis can be further categorized as:

• Congenital: Including erythropoietin receptor mutations and defects in oxygen-sensing pathways (VHL, PHD2, HIF2A mutations) 3
• Acquired: Including polycythemia vera (the only established form of primary acquired erythrocytosis) and various secondary causes 2, 4

Common Causes of Secondary Erythrocytosis

Secondary erythrocytosis can result from various conditions:

• Kidney-related causes: Cystic kidney diseases, erythropoietin-secreting neoplasms, renal artery stenosis, IgA nephropathy, post-kidney transplant erythrocytosis 5
• Medication-induced: Erythropoietin-stimulating agents, androgen therapy, SGLT2 inhibitors 5
• Respiratory causes: Chronic lung disease, obstructive sleep apnea, high-altitude exposure 5
• Other factors: Heavy smoking, dehydration 6, 5

Clinical Implications of Erythrocytosis

Erythrocytosis has significant effects on multiple organ systems:

• Cardiovascular effects: Increased blood viscosity affecting circulation and potentially leading to thrombotic events 7
• Renal effects: Compromised renal function due to altered hemodynamics and microcirculation; glomeruli become hypercellular and congested, potentially progressing to sclerosis 7
• Symptoms of hyperviscosity: Headache, fatigue, poor concentration, and risk of thrombotic complications 6

Management Considerations

Management should be guided by severity and underlying cause:

• Phlebotomy indications: Only recommended when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with associated hyperviscosity symptoms and no dehydration 6
• Hydration: Maintaining adequate hydration is critical to mitigate negative effects of increased blood viscosity 6, 7
• Medication considerations: Use caution with medications affecting renal function in patients with erythrocytosis 7
• Monitoring: Regular assessment of complete blood counts and renal function 6, 7
• Aspirin therapy: Consider low-dose aspirin if no contraindications exist, especially in cases secondary to myeloproliferative disorders 6

Common Pitfalls to Avoid

• Unnecessary phlebotomy: Performing routine phlebotomies without meeting established criteria can lead to iron deficiency 6
• Iron depletion: Excessive phlebotomy can paradoxically worsen symptoms by reducing oxygen-carrying capacity and red cell deformability 6
• Inadequate hydration: Dehydration can exacerbate erythrocytosis and its complications 6, 7
• Overlooking underlying causes: Failing to identify and address the root cause of secondary erythrocytosis 1