From the Guidelines
The workup for elevated hemoglobin (Hgb) should begin with a thorough history and physical examination, followed by targeted laboratory testing to rule out secondary causes and identify potential primary causes such as polycythemia vera. The initial step is to confirm the elevation with repeat complete blood count (CBC) and assess for secondary causes including smoking, high altitude living, chronic lung disease, sleep apnea, and dehydration 1. Essential laboratory tests include:
- Serum erythropoietin level
- JAK2 V617F mutation testing
- Arterial blood gas analysis
- Iron studies (ferritin, transferrin saturation) Additional testing should include:
- Comprehensive metabolic panel
- LDH
- Uric acid levels If secondary causes are ruled out and primary polycythemia is suspected, consider bone marrow biopsy and additional genetic testing for JAK2 exon 12, CALR, and MPL mutations 1. Imaging studies such as abdominal ultrasound to evaluate spleen size and CT scans to rule out renal or hepatic tumors may be necessary. Management depends on the underlying cause - addressing secondary factors when identified or implementing phlebotomy and possibly cytoreductive therapy like hydroxyurea for polycythemia vera. Elevated hemoglobin requires thorough investigation as it may indicate serious underlying conditions including polycythemia vera, which carries increased risk of thrombosis and progression to myelofibrosis or leukemia. It is crucial to consider factors such as altitude, age, race, and smoking when interpreting Hgb values, as these can contribute to variations in normal ranges 1. The current definition of anemia and target Hgb levels for Epoetin therapy may also inform the workup and management of elevated Hgb, although these guidelines are primarily focused on anemia in chronic kidney disease 1.
From the Research
Workup for Elevated Hemoglobin
Elevated hemoglobin (Hgb) levels can be an indicator of various conditions, including polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2, 3, 4. The workup for elevated Hgb involves several steps:
- Complete Blood Cell Count (CBC): A CBC is typically the first step in evaluating elevated Hgb levels. It measures various components of the blood, including red blood cell count, white blood cell count, and platelet count 5.
- Hemoglobin and Hematocrit Levels: Measuring hemoglobin and hematocrit levels is crucial in diagnosing PV. The World Health Organization's major diagnostic criteria include an elevated hemoglobin or hematocrit level, abnormal results on bone marrow biopsy, and presence of the Janus kinase 2 genetic mutation 4.
- Bone Marrow Biopsy: A bone marrow biopsy is essential in diagnosing PV and other myeloproliferative neoplasms. It helps identify abnormal cell morphology and genetic mutations 3, 4.
- Janus Kinase 2 (JAK2) Mutation Testing: The JAK2 mutation is present in approximately 98% of PV cases. Testing for this mutation can help differentiate PV from secondary causes of erythrocytosis 4.
- Erythropoietin Level: Measuring erythropoietin levels can help differentiate PV from common causes of secondary erythrocytosis, such as smoking, sleep apnea, and testosterone use 4.
- Clinical Evaluation: A thorough clinical evaluation, including medical history, physical examination, and laboratory tests, is necessary to identify underlying conditions that may be contributing to elevated Hgb levels 2, 3, 4.
Differential Diagnosis
The differential diagnosis for elevated Hgb levels includes:
- Polycythemia Vera (PV): A myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2, 3, 4.
- Secondary Erythrocytosis: Caused by conditions such as smoking, sleep apnea, and testosterone use 4.
- Other Myeloproliferative Neoplasms: Such as essential thrombocythemia (ET) and primary myelofibrosis (PMF) 3.
Management
The management of elevated Hgb levels depends on the underlying cause. For PV, treatment typically involves: