Description

• Increase in hemoglobin (Hgb) above the normal range:
  • Men: Hgb >16.5 g/dL, hematocrit (Hct) >49%
  • Women: Hgb >16 g/dL, Hct >48%
• Symptoms are related to blood viscosity, which increases exponentially at Hct >60%

Etiology

• Relative (apparent) polycythemia:
  • Resulting from decrease in plasma volume
  • Acute: Dehydration
  • Chronic: Gaisböck syndrome (stress polycythemia): Obese, hypertensive, middle-aged smokers
• Primary erythrocytosis:
  • Polycythemia vera (PV): A stem cell disorder characterized by panhyperplasia of all bone marrow elements leading to increased production of RBCs, WBCs, and platelets. Erythrocytosis is the most prominent feature:
    • Mutation in the tyrosine kinase (JAK2), which acts in signaling pathways of the EPO-receptor, rendering those cells hypersensitive to erythropoietin
    • Median age 60, 5% <40, peak in 70s
    • Higher in Ashkenazi Jews and lower in Asians and African Americans
    • Median survival ∼14 yr
    • May progress to myelofibrosis or acute leukemia
• Secondary polycythemia:
  • Central hypoxia increasing erythropoietin:
    • Chronic pulmonary disease
    • Sleep apnea (5–10% have high Hgb)
    • Obesity hypoventilation syndrome (Pickwickian syndrome)
    • Congenital heart disease (right-to-left shunt)
    • High altitude (chronic)
    • Smoker's erythrocytosis
    • Carbon monoxide poisoning (chronic)
    • Chronic methemoglobinemia
  • Renal-mediated causes of increased erythropoietin production:
    • Renal cell carcinoma
    • Renal artery atherosclerotic narrowing
    • Focal glomerulonephritis
    • Postrenal transplant with or without rejection
    • Chronic hydronephrosis
    • Polycystic kidney disease and renal cysts
  • Inappropriate autonomous erythropoietin production:
    • Hepatomas
    • Cerebellar hemangioblastoma
    • Wilms tumor
    • Parathyroid carcinoma and adenoma
    • Ovarian tumors
    • Adrenal adenomas and carcinomas (pheochromocytoma, Cushing syndrome)
    • Uterine leiomyomata
  • Blood doping:
    • Recombinant erythropoietin abuse
    • Autologous transfusions
  • Drug abuse:
    • Chronic cocaine abuse
    • Androgenic steroids
• Genetic disorders with polycythemia:
  • High-affinity Hgb variants
  • Bisphosphoglycerate deficiency
  • von Hippel–Lindau syndrome
  • Chuvash polycythemia
  • Erythropoietin-receptor mutations
  • Congenital methemoglobinemia
• Infections:
  • Viral hepatitis, AIDS

• Major criteria:
  • Hgb >16.5 g/dL in men, >16 g/dL in women
  • BM trilineage myeloproliferation
  • Presence of JAK2 mutation
• Minor criteria:
  • Low serum erythropoietin level
• Adjuncts to diagnosis:
  • Platelets >400,000/mm³
  • ANC >10,000 (WBC >12,000/mm³)
  • Splenomegaly on exam or CT imaging
  • Leukocyte alkaline phosphatase elevation
  • B₁₂ >900 pg/mL; unbound vitamin B₁₂-binding capacity >2,200 pg/mL