What lab tests are included in the initial work up of patients with an elevated hemoglobin (Hb) or hematocrit (Hct)?

By William Aird

First-line testing:

  • Complete blood count
  • Peripheral blood smear
  • Renal function
  • Liver function
  • Arterial oxygen saturation
  • Carboxyhemoglobin
  • Serum ferritin
  • Serum erythropoietin:
    • A low erythropoietin level (< 2.9 mU/mL) specific (92%) and moderately sensitive (64%) for the diagnosis of polycythemia vera.
    • A high erythropoietin level (> 15.1 mU/mL) specific (98%) but had poor sensitivity (47%) for the diagnosis of secondary erythrocytosis.
  • Jak2 mutational analysis (peripheral blood) – based on the pretest probability of polycythemia vera (PV):
    • In the primary care setting, where the probability of PV is low, clinical evaluation for secondary causes of erythrocytosis paired with a high erythropoietin level can rule out PV in most patients.
    • In hematology clinics, where the probability of PV is higher, erythropoietin level and JAK2 V617F mutation testing are done concurrently.
    • Patients with a low or normal erythropoietin level and no JAK2 V617F mutation are further evaluated with JAK2 exon 12 mutation testing (on peripheral blood or marrow aspirate, based on local practice) and a bone marrow biopsy.

Second-line testing:

  • When no diagnosis is made, selected patients with onset of erythrocytosis at a young age or compatible family history should undergo testing for high-oxygen-affinity hemoglobins, and gene sequencing for mutations involving the erythropoietin receptor or oxygen-sensing pathways.
  • Investigations for secondary erythrocytosis should be symptom directed and may include:
    • Chest radiography
    • Overnight oximetry for suspected sleep apnea
    • Pulmonary function tests for hypoxic lung disease
    • Venous blood gas sampling (carboxyhemoglobin level)
    • Echocardiography to rule out right to left cardiac shunting
    • Abdominal–pelvic imaging can help exclude an erythropoietin-producing tumor or conditions associated with local renal hypoxia.
    • Neuroimaging to rule out meningioma or cerebellar hemangioblastoma should be ordered for patients with unexplained neurologic symptoms as these tumors have been associated with autonomous erythropoietin production.
CXR, chest X ray.

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