From the Guidelines
The diagnostic workup for polycythemia should begin with a complete blood count (CBC) to confirm elevated hemoglobin and hematocrit, followed by serum erythropoietin levels, JAK2 mutation analysis, and bone marrow biopsy with aspirate, as recommended by the most recent and highest quality study 1. The initial step in the diagnostic workup for polycythemia is to confirm the presence of erythrocytosis through a CBC, which measures hemoglobin and hematocrit levels.
- Hemoglobin levels above 16.5 g/dL in men and 16.0 g/dL in women, and
- Hematocrit levels above 49% in men and 48% in women, are indicative of erythrocytosis. After confirming erythrocytosis, the next step is to distinguish between primary polycythemia (such as polycythemia vera) and secondary causes.
- Testing should include serum erythropoietin levels to determine if the erythrocytosis is due to increased erythropoietin production.
- JAK2 mutation analysis (particularly V617F and exon 12 mutations) should also be performed, as the presence of a JAK2 mutation is highly suggestive of polycythemia vera 1.
- Bone marrow biopsy with aspirate may also be necessary to evaluate bone marrow histology and cytogenetics. If erythropoietin is low or normal with positive JAK2 mutation, polycythemia vera is likely.
- In such cases, additional tests such as hemoglobin electrophoresis for abnormal hemoglobins with high oxygen affinity and testing for rare mutations in the erythropoietin receptor gene may be necessary to confirm the diagnosis. If erythropoietin is elevated, secondary causes should be investigated through:
- Arterial blood gas analysis to assess oxygen saturation
- Abdominal ultrasound to evaluate kidneys and liver
- Sleep studies for sleep apnea
- Pulmonary function tests
- Chest imaging This systematic approach helps differentiate between primary polycythemia, which is a myeloproliferative neoplasm, and secondary polycythemia, which results from physiological responses to hypoxia or abnormal erythropoietin production 1.
From the Research
Diagnostic Workup for Polycythemia
The diagnostic workup for polycythemia, a condition characterized by an excessive red blood cell count, involves several key steps and considerations.
- Major Diagnostic Criteria: According to the World Health Organization, the major diagnostic criteria for polycythemia vera include an elevated hemoglobin or hematocrit level, abnormal results on bone marrow biopsy, and the presence of the Janus kinase 2 (JAK2) genetic mutation, which is present in approximately 98% of cases 2.
- Minor Diagnostic Criterion: A subnormal erythropoietin level is considered a minor criterion, helping to differentiate polycythemia vera from common causes of secondary erythrocytosis such as smoking, sleep apnea, and testosterone use 2.
- Bone Marrow Morphology: Bone marrow morphology remains a cornerstone of diagnosis, with the presence of JAK2, CALR, or MPL mutations being significant in essential thrombocythemia (ET) and polycythemia vera (PV) 3, 4, 5, 6.
- Molecular Markers: The presence of specific molecular markers such as JAK2, CALR, and MPL mutations can help in the diagnosis and differentiation of PV and ET from other conditions 3, 4, 5, 6.
- Risk Stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis, with factors such as age, thrombosis history, and the presence of certain mutations influencing risk category 3, 5, 6.
- Differential Diagnosis: Differential diagnosis for ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis, highlighting the need for careful evaluation 4, 5.
Key Diagnostic Tests
- Complete Blood Count (CBC): To assess red blood cell count, hemoglobin, and hematocrit levels.
- Bone Marrow Biopsy: To evaluate bone marrow morphology and detect any abnormalities.
- Genetic Mutation Testing: To identify the presence of JAK2, CALR, or MPL mutations.
- Erythropoietin Level Test: To help differentiate primary from secondary erythrocytosis.
Considerations
The diagnostic workup for polycythemia must consider the patient's overall clinical presentation, medical history, and the presence of any symptoms suggestive of myeloproliferative neoplasms. The identification of specific genetic mutations and the assessment of bone marrow morphology are critical for an accurate diagnosis and for guiding treatment decisions 2, 3, 4, 5, 6.