Polycythemia
Introduction
What is Polycythemia ?
Polycythemia is an increased hemoglobin (Hgb) concentration and/or hematocrit (Hct) in peripheral blood. It is also called erythrocytosis.
When do you call a patient to have polycythemia?
According to the WHO definition, polycythemia is defined as serum hematocrit or hemoglobin exceeding normal ranges expected for age and sex.
Hct > 49% in healthy adult men and >48% in women, or
Hgb >16.5g/dL in men or >16.0g/dL in women.
In British literature, polycythemia is defined as Hct >52% in males and >48% in females.
What are different types of Polycythemia?
Polycythemia can be mainly divided into 2 main types.
1. True polycythemia
2. Relative polycythemia
What is the difference between these 2 types of Polycythemia?
1. ‘True’ polycythemia (or absolute erythrocytosis) refers to a real increase in RBC mass. It is due to multiple causes and can be categorized as either primary or secondary polycythemia.
– Primary polycythemia – Primary polycythemia refers to an increase of RBC mass caused by a mutation (either acquired or inherited) in RBC progenitor cells.
– Secondary polycythemia – Secondary polycythemia refers to an increase of RBC mass caused by elevated serum EPO due to some reason.
2. Relative polycythemia – An elevation of Hb and/or Hct due to a decrease in plasma volume alone (hemoconcentration). There is no increase in the RBC mass.
What are the causes of relative polycythemia?
Relative polycythemia is an apparent increase in Hct without an actual increase. This is due to a reduction in plasma volume while red cell mass is normal.
This may occur acutely, such as due to dehydration, or chronically, associated with obesity, HTN, and a high alcohol and tobacco intake.
What is Gaisböck's syndrome?
Gaisböck’s syndrome is also referred to as spurious polycythemia or stress polycythemia. Classically, this was described as polycythemia in anxious patients with hypertension, no splenomegaly, and reduced plasma volume. However, hypertension with diuretic use and smoking may account for the relative polycythemia in many of these individuals. Smoking should be discontinued in all such patients.
Please elaborate absolute polycythemia?
Absolute polycythemia is an actual increased RBC mass. RBC mass is classically measured by dilution of infused autologous radioactive chromium (51Cr) labeled RBCs.
Primary – when the problem lies within RBC itself. RBC autonomously proliferate without a need for EPO. e.g., in polycythemia vera. EPO production and thus serum levels are reduced through negative feedback.
Secondary – there is increased EPO leading to erythrocytosis. This increased EPO is secondary to either hypoxic conditions (e.g., high altitudes, chronic lung disease, cyanotic congenital heart disease, heavy smoking) or due to ectopic secretion of EPO (e.g., in renal carcinoma, hepatocellular carcinoma, ovarian fibroma, hemangioblastoma).
What are the clinical features?
Polycythemia may be asymptomatic and detected on complete blood counts (CBC) accidentally.
It may also present with vague symptoms due to hyperviscosity: headaches, dizziness, tinnitus, and visual disturbance. Facial plethora may be obvious.
Patients with polycythemia rubra vera (PRV) can have some characteristic features like aquagenic pruritus (itching after exposure to water), erythromelalgia (a burning sensation in fingers and toes), splenomegaly (in up to 60%), and gout (due to high red cell turnover). They have an increased risk of arterial thromboses, particularly stroke, and venous thromboembolism.
How is polycythemia assessed?
Assess whether polycythemia is relative or absolute.
The presence of hypertension, smoking, excess alcohol consumption, and/or diuretic use is consistent with low-volume polycythemia (Gaisböck syndrome). A history of diarrhea and vomiting also points toward polycythemia secondary to hemoconcentration.
On the contrary, males and females with Hct values of over 0.60 and over 0.56, respectively, can be assumed to have true polycythemia or absolute erythrocytosis.
Measuring EPO levels will help distinguish between primary and secondary polycythemia. In primary, it is expected to be low while in secondary it will be high.
In secondary polycythemia, clinical history and examination including measurement of oxygen saturation will identify most patients with polycythemia secondary to hypoxia. If no stimulus for increased erythropoietin levels is found (absence of cardiopulmonary, renal disease, etc), then look for tumors that can be the reason for ectopic erythropoietin production (renal cell carcinoma, hepatocellular carcinoma, ovarian fibroma, hemangioblastoma).
In primary polycythemia, polycythemia rubra vera (PRV) is the main differential. The acquired V617F mutation is found in the JAK-2 gene in over 90% of cases. In the remainder, mutations in exon 12 of the same gene may be identified.
Bone marrow examination may be needed in some cases of primary polycythemia.
How is polycythemia treated?
In relative polycythemia, manage the causative factors like obesity, hypertension, smoking, treatment, and rehydration in diarrhea/vomiting, etc.
In secondary polycythemia, again treatment is the treatment of the cause. e.g. management of cardiopulmonary diseases, renal diseases, and cessation of smoking. Treatment of the tumors which are making ectopic erythropoietin. Venesection is done (250 ml) where there are cumbersome symptoms. Care shall be taken not to lower Hct too low in patients with cardiopulmonary disease, as it may worsen their dyspnea.
In primary polycythemia, the aim is to keep HCT <0.45 to decrease the risk of thrombosis. In younger patients at low risk, this is done by venesection. If higher risk (age >60yrs, previous thrombosis), hydroxyurea is also used along with venesections.
Pegylated interferon is preferred in women of childbearing age.
Aspirin, daily low dose, is given in all patients of primary polycythemia, and those with cardiovascular risk factors in secondary polycythemia for thrombosis prophylaxis.
