Laboratory Studies
Testing for the JAK2 V617F mutation and an erythropoietin (EPO) level helps differentiate secondary polycythemia from polycythemia vera. [22, 23] Positive JAK2 V617F mutation status with a low EPO level confirms the diagnosis of polycythemia vera. If JAK2 V617F mutation testing is negative but the EPO level is low, then testing for other mutations in exon 12 and 13 of JAK2 helps identify a small minority of patients with polycythemia vera. All the other patients with wild-type JAK2 and a normal or elevated EPO level have secondary polycythemia.
Measure red blood cell mass and plasma volume when repeated hematocrit levels exceed 52% in males and 47% in females. However, data from the Polycythemia Vera Study Group showed that if the hematocrit value is 60% or higher, the red blood cell mass is always increased; formal red blood cell mass and plasma volume studies are unnecessary in those cases. As a practical note, most nuclear medicine departments perform these tests very infrequently, which may raise questions about the reliability and validity of red blood cell mass and plasma volume measurements.
To measure red blood cell mass, calculate the total red blood cell mass from the dilution factor and a known volume of radiolabeled (chromium-51 [51 Cr]) autologous red blood cells. The red blood cell mass is increased if it exceeds 35 mg/kg in males and 31 mg/kg in females. Documentation of an increased red blood cell mass is essential to demonstrate true erythrocytosis.
To measure plasma volume, use radiolabeled albumin (iodine-131 [131 I]), similar to the process used with the red blood cell mass measurement. Plasma volume can also be calculated indirectly using total red blood cell mass and the hematocrit value.
Decreased plasma volume with a normal red blood cell mass indicates a relative polycythemia or erythrocytosis, similar to the increased hemoglobin and hematocrit levels associated with severe dehydration. Decreased plasma volume due to dehydration is the most common cause of elevated hemoglobin or hematocrit levels in the general population.
Measuring arterial oxygen saturation is important to exclude generalized hypoxemia as a cause of increased red blood cell mass. Further investigation may require performing the test while the patient is sleeping. Measured arterial oxygen saturations of less than 92% may be associated with the development of a secondary polycythemia.
Carboxyhemoglobin levels of greater than 8% in individuals who smoke or those who may have an occupational exposure to carbon monoxide may be associated with the development of polycythemia.
The hemoglobin-oxygen dissociation curve may be determined in patients with a lifelong history (particularly a familial history) of erythrocytosis with normal oxygen saturation and normal levels of 2,3-diphosphoglycerate.
Formulas are available in which the measured arterial and venous oxygen saturations can be used to calculate the partial pressure of oxygen (PaO2) at which hemoglobin is 50% saturated with oxygen. This partial pressure value is a good estimate of the entire oxygen dissociation curve, because the shape of the dissociation curve varies only minimally, even with very high and very low oxygen affinity hemoglobins.
Endogenous serum levels of EPO may be helpful to determine inappropriate production of EPO. Serum EPO levels also may be very helpful in distinguishing between primary and secondary polycythemias. [7, 24]
In polycythemia vera and congenital/familial primary polycythemias, EPO levels are usually low to low-normal. In secondary physiologic or nonphysiologic polycythemias, EPO levels are usually normal or elevated.
Imaging Studies
An abdominal computed tomography (CT) scan or an intravenous pyelogram to investigate the kidneys and their function may be indicated in a minority of patients who may have a tumor or renal abnormalities that may be causing the polycythemia.
