From the Guidelines
Elevated hemoglobin and hematocrit levels, along with an increased red blood cell count, require therapeutic phlebotomy only when the hemoglobin is greater than 20 g/dL and the hematocrit is greater than 65%, associated with symptoms of hyperviscosity, as stated in the acc/aha 2008 guidelines 1. In patients with elevated H&H and RBC count on CBC, it is crucial to assess for symptoms of hyperviscosity, such as headache, increasing fatigue, or other related symptoms, in the absence of dehydration or anemia. Key considerations include:
- Confirming the elevation with repeat testing to rule out dehydration, which can cause falsely elevated values
- Evaluating for underlying causes of polycythemia, including primary polycythemia (polycythemia vera) and secondary causes such as chronic hypoxemia, certain kidney diseases, or erythropoietin-producing tumors
- Ordering additional tests, such as erythropoietin levels, JAK2 mutation analysis, arterial blood gases, and abdominal ultrasound, to determine the underlying cause
- Avoiding repetitive routine phlebotomies due to the risk of iron depletion, decreased oxygen-carrying capacity, and stroke, as recommended by the acc/aha 2008 guidelines 1
- Monitoring for iron deficiency, even in the face of erythrocytosis, as it can lead to reduced oxygen-carrying capacity and increased risk of stroke, and treating it with caution, as oral administration of iron can result in a rapid increase in red cell mass 1.
From the Research
Elevated H&H and RBC CBC
Elevated hemoglobin (H) and hematocrit (Hct) levels, along with an increased red blood cell (RBC) count, can be indicative of several conditions.
- The most common causes include:
- Dehydration
- Polycythemia vera (PV)
- Essential thrombocythemia (ET)
- Secondary polycythemia
- According to the study 2, the diagnosis of polycythemia vera requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis.
- The JAK2(V617F) mutation is found in 95% of PV cases, and functionally similar mutations in JAK2 exon 12 have also been described 2, 3.
- A study 4 compared the clinicopathologic and molecular features of patients with early prepolycythemic phase of polycythemia vera (e-PV) with those of patients with essential thrombocythemia (ET) and polycythemia vera (PV), and found that patients with e-PV were characterized by an increase in red cell parameters, splenomegaly, and hepatomegaly, together with hypercellular bone marrow due to increased erythropoiesis and granulopoiesis.
Diagnostic Considerations
- The frequency of the JAK2V617F mutation was similar in e-PV and PV, but was significantly lower in ET 4.
- A low erythropoietin level and JAK2 mutation showed comparable positive predictive value for true polycythemia 5.
- A very-low erythropoietin level had a positive predictive value of 100% for polycythemia vera diagnosis 5.
- The JAK2 V617F point mutation makes normal hematopoietic progenitor cells hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells, leading to trilinear hematopoietic myeloproliferation 6.
Bone Marrow Morphology
- Bone marrow morphologic features, such as erythroid hyperplasia and subtle megakaryocytic atypia, can be helpful in diagnosing polycythemia vera 2, 4.
- The presence of small, atypical megakaryocytes and abnormal chromatin distribution can be seen in patients with JAK2 exon 12 mutations 2.
- Hypercellular bone marrow with erythroid hyperplasia and megakaryocytic hyperplasia can be seen in patients with polycythemia vera and essential thrombocythemia 4, 6.