From the Guidelines
To investigate polycythemia, I recommend ordering a complete blood count (CBC) with differential, erythropoietin (EPO) levels, and JAK2 V617F mutation testing as the initial tests to confirm elevated hemoglobin and hematocrit levels and distinguish between primary and secondary causes.
Initial Tests
- Complete blood count (CBC) with differential to confirm elevated hemoglobin and hematocrit levels 1
- Erythropoietin (EPO) levels to help differentiate between primary and secondary polycythemia 1
- JAK2 V617F mutation testing, which is present in up to 97% of polycythemia vera cases 1
Additional Tests
- Bone marrow biopsy to examine bone marrow histology and cytogenetic studies 1
- Arterial blood gas analysis to assess oxygen saturation
- Comprehensive metabolic panel to evaluate organ function
- Serum ferritin to check iron stores
- Abdominal ultrasound to examine the spleen and liver
- Chest imaging to rule out pulmonary causes
Tests for Secondary Causes
- Sleep studies if sleep apnea is suspected
- Renal ultrasound for kidney tumors
- Carboxyhemoglobin levels if carbon monoxide exposure is possible These tests help differentiate between polycythemia vera (a myeloproliferative neoplasm) and secondary polycythemia caused by hypoxia, EPO-producing tumors, or other conditions 1. The pattern of results, particularly the relationship between EPO levels and red cell mass, provides crucial diagnostic information to guide appropriate treatment. In equivocal cases, additional specialized tests such as bone marrow examination with cytogenetic studies, demonstration of markedly decreased megakaryocyte expression of the TPO receptor (c-mpl), or peripheral blood neutrophil assay for PRV-1 expression may be necessary to confirm the working diagnosis of polycythemia vera 1.
From the Research
Laboratory Tests for Polycythemia Investigation
The following laboratory tests are indicated for the investigation of polycythemia:
- Complete blood count (CBC) to determine hematocrit and hemoglobin levels 2, 3, 4, 5
- Serum erythropoietin (EPO) level to distinguish primary and secondary polycythemia 2, 3, 4, 6
- JAK2 mutation test to confirm the diagnosis of polycythemia vera (PV) 2, 3, 4, 6
- Bone marrow biopsy to evaluate bone marrow morphology and confirm the diagnosis of PV 2, 4
- Measurement of red blood cell mass and plasma volume to differentiate primary, secondary, and combined polycythemia 5
Additional Tests
Additional tests may be necessary to rule out secondary causes of polycythemia, such as:
- Chest x-ray to evaluate for underlying lung disease 5
- Computed tomography (CT) scan to evaluate for thrombotic events 2
- Blood smear evaluation to assess for abnormalities in blood cell morphology 4
Diagnostic Criteria
The World Health Organization (WHO) consensus criteria for diagnosing PV require the presence of two major criteria and one minor criterion or the presence of the first major criterion and two minor criteria 2. Decreased EPO is considered a minor WHO criterion for PV diagnosis 2. However, it is essential to note that PV can present with a high or low serum EPO level, and further diagnostic tests are usually required to confirm the final diagnosis 2, 6.