What are the implications of elevated hemoglobin (Hb) levels with a normal red blood cell (RBC) count?

From the Guidelines

Elevated hemoglobin levels with a normal red blood cell count are not typically a cause for concern unless the hemoglobin is greater than 20 g/dL and the hematocrit is greater than 65%, in which case therapeutic phlebotomy may be necessary to relieve symptoms of hyperviscosity. This is based on the recommendations from the American College of Cardiology/American Heart Association task force on practice guidelines, as outlined in the 2008 guidelines for the management of adults with congenital heart disease 1.

Key Considerations

• The increase in red blood cell mass that accompanies cyanosis is a compensatory response to improve oxygen transport, and most cyanotic patients have compensated erythrocytosis with stable hemoglobin that requires no intervention 1.
• Therapeutic phlebotomy is usually unnecessary unless the hemoglobin is more than 20 g/dL and the hematocrit is greater than 65% with associated symptoms of hyperviscosity and no evidence of dehydration 1.
• Repetitive phlebotomies deplete iron stores and may result in production of iron-deficient red blood cells, which is undesirable due to the reduced oxygen-carrying capacity and deformability of red blood cells and increased risk of stroke 1.

Management

• If symptoms like headaches, poor concentration, or other symptoms of hyperviscosity occur, removal of 1 unit of blood with equal volume replacement of dextrose or saline may be necessary to relieve symptoms 1.
• Iron deficiency in a patient with destabilized erythropoiesis should be treated with caution, and oral administration of iron should be monitored closely to avoid a rapid increase in red cell mass 1.
• In some cases, patients may be intolerant of oral iron and should be placed on pulses of intravenous iron supplementation instead 1.

From the Research

Implications of Elevated Hemoglobin (Hb) Levels with a Normal Red Blood Cell (RBC) Count

• Elevated hemoglobin levels with a normal RBC count can be an indicator of polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2, 3.
• PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia 2, 4.
• The presence of a JAK2 gene variant is a key diagnostic criterion for PV, and is found in almost all cases of PV 2, 4.
• Elevated hemoglobin levels can also be seen in other conditions, such as alpha-thalassemia, where the Hct/Hb ratio is higher than normal 5.
• Red blood cells play a significant role in hemostasis and thrombosis, and changes in RBC counts or qualitative changes can affect bleeding and thrombosis 6.

Diagnostic Considerations

• A diagnosis of PV should be considered in patients with elevated hemoglobin levels and a normal RBC count, particularly if they have a JAK2 gene variant 2, 3.
• Other conditions, such as alpha-thalassemia, should also be considered in the differential diagnosis 5.
• A direct measurement of red cell mass and plasma volume can help establish the correct diagnosis in cases where the hematocrit is normal 3.

Therapeutic Implications

• Patients with PV should receive therapeutic phlebotomy to maintain a hematocrit of less than 45% and low-dose aspirin to reduce the risk of thrombosis 2.
• Cytoreductive therapies, such as hydroxyurea or interferon, may be recommended for patients at high risk of thrombosis 2.
• Ruxolitinib, a Janus kinase inhibitor, can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea 2.