Inappropriately Elevated Serum Erythropoietin (see Serum Erythropoietin, Serum Erythropoietin)



Appropriately Elevated Serum Erythropoietin (see Serum Erythropoietin, Serum Erythropoietin)

Hypoxemia of Any Etiology (see Hypoxemia, Hypoxemia)

Germline/Somatic Mutations

  • 2,3 Bisphosphoglycerate (BPG) Mutase Deficiency
  • Activating Mutations of the Erythropoietin Receptor (EPOR) Gene
  • Chuvash Polycythemia (VHL Gene Mutation)
  • Congenital Methemoglobinemia (see Methemoglobinemia, Methemoglobinemia)
  • HIF2α Gene Mutation
  • High Oxygen Affinity Hemoglobins
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  • Idiopathic Familial Polycythemia
  • PHD2 Gene Mutation
  • Polycythemia Vera (see Polycythemia Vera)



General Comments

  • Hemoglobin and Hematocrit are Dependent on Red Blood Cell Mass and Plasma Volume

Erythropoietin Synthesis

  • Approximately 90% of Erythropoietin is Synthesized by the Kidneys in Response to Hypoxia
    • Mechanisms of Activation of Erythropoietin-Producing Cells
      • Decreased Serum Hemoglobin (Anemia): as in the case of anemia
      • Decreased Hemoglobin Saturation (Hypoxemia): as in the case of hypoxemia
      • Decreased Oxygen Release from Hemoglobin: as in the case of hemoglobinopathy
      • Decreased Oxygen Delivery to the Kidney: as in the case of renal artery stenosis, etc
    • Erythropoietin-Dependence of Polycythemic States
      • Erythropoietin-Independent Erythrocytosis (As Occurs in Polycythemia Vera) Inhibits Renal Erythropoietin Synthesis, Resulting in Decreased Serum Erythropoietin Levels
      • Erythropoietin-Dependent Erythropoiesis (As Occurs in Hypoxia or with an Erythropoietin-Secreting Tumor) Causes Secondary Erythrocytosis, Resulting in Normal-High Serum Erythropoietin Levels

Types of Polycythemia

  • Relative Polycythemia (Gaisbock’s Disease, Spurious Polycythemia, Stress Erythrocytosis, Apparent Polycythemia, and Pseudopolycythemia): defined as an isolated decrease in plasma volume
    • Elevated Hemoglobin
    • Elevated Hematocrit
    • Elevated Red Blood Cell Count
  • Absolute Polycythemia (Erythrocytosis): defined as an increase in red blood cell mass
    • Primary Polycythemia: due to an abnormality within red blood cell progenitors
    • Secondary Polycythemia: due to a circulating erythropoietic factor (usually erythropoietin)
  • Combined Polycythemia: due to both a decrease in plasma volume and an increase in red blood cell mass
    • This Combination is Most Commonly Observed in Smokers (“Smokers Polycythemia”)
  • Inapparent Polycythemia: defined as an equivalent increase in both the red blood cell mass and plasma volume
    • Hemoglobin, Hematocrit, and Red Blood Cell Count All Remain Normal: therefore, polycythemia can only be diagnosed by blood volume studies (using isotopic dilution or other methods)


Complete Blood Count (CBC) (see Complete Blood Count, Complete Blood Count)

  • Hemoglobin
    • Hemoglobin >16.5 g/dL: defined as polycythemia in males
    • Hemoglobin >16.0 g/dL: defined as polycythemia in females
  • Hematocrit
    • Hematocrit >49%: defined as polycythemia in males
    • Hematocrit >48%: defined as polycythemia in females
  • Red Blood Cell Count: not used as often as hemoglobin and hematocrit in the diagnosis of polycythemia (since diseases such as thalassemia minor may have an elevated red blood cell count with a decreased hemoglobin or hematocrit due to an increased number of small/microcytic, poorly hemoglobinized/hypochromic red blood cells)

Serum Erythropoietin (see Serum Erythropoietin, Serum Erythropoietin)

  • xxxxx

Clinical Manifestations

Clinical Manifestations of Polycythemia Vera


  • Pulmonary hypertension secondary to thrombocytosis in a patient with myeloid metaplasia. Chest 1993; 103:642– 4
  • Pulmonary hypertension in polycythemia vera. Am J Hematol 1994;47:242–4
  • Unexplained pulmonary hypertension in chronic myeloproliferative disorders. Chest 2001;120:801– 8