Polycythemia (erythrocytosis)

Learning objectives

Polycythemia or erythrocytosis is an increase in red blood cell mass, and is associated with an increase in hemoglobin concentration (Hb) and hematocrit (Hct)
The condition increases blood viscosity and can reduce cerebral blood flow

Absolute polycythemia (increased red cell mass)
- Primary (polycythemia vera; PV)
- Secondary
- Idiopathic
Apparent polycythemia (normal red cell mass)
- Reduced plasma volume

PV is characterized by the clonal proliferation of myeloid cells
>95% of patients have a genetic mutation of JAK2 → stimulates overproduction of erythrocytes, platelets, and granulocytes
JAK2 mutation is not specific for PV, also found in patients with primary thrombocytosis and primary myelofibrosis
Clinical manifestations result from thrombotic episodes secondary to increased blood viscosity
Production of immature platelets with variable function and acquired von Willebrand’s disease (vWD) are thought to be behind the bleeding tendency
Associated laboratory findings
- Thrombocytosis
- Leukocytosis
- Elevated lactate dehydrogenase
Clinical features
- Hypertension (46%)
- Splenomegaly (36%)
- Pruritus (36%)
- Erythromelalgia (29%)
- Arterial thrombosis (16%)
- Venous thrombosis (7%)
- Hemorrhage (4%)
- Facial plethora
- Hepatomegaly
- Gout

Increased red cell mass is due to increased erythropoietin (EPO) production
Compensatory mechanism in response to chronic tissue hypoxia or inappropriate production of EPO by the kidneys
Causes include
- Chronic obstructive pulmonary disease (COPD)
- Obstructive sleep apnea (OSA)
- Cyanotic heart disease
- Altitude
- Renal artery stenosis
- Renal tumors
- Transplanted kidneys

Increased red cell mass without an identifiable cause
Patients are more commonly male and >50% present with vascular occlusive complications

Reduced plasma volume results in an increased Hct and Hb on laboratory tests, but the red cell mass is normal
Associated with the following clinical conditions
- Obesity
- Hypertension
- Smoking
- Excessive alcohol intake
- Diuretic use

Measurement	Male	Female
Hemoglobin (g/L)	>185	>165
Hematocrit	>0.52	>0.48

Classification	Treatment
Primary polycythemia	Reduce the risk of thrombosis, hemorrhage, and transformation to acute leukemia or myelofibrosis Phlebotomy or venesection (Hct <0.45) and aspirin Consider hydroxyurea or interferon alpha if the above treatments fail
Secondary polycythemia	Phlebotomy and management of the underlying condition (if possible)
Idiopathic polycythemia	Phlebotomy, cytoreductive therapy is contraindicated
Apparent polycythemia	Lifestyle modification and phlebotomy (if required)