Erythrocytosis and polycythemia rubra vera – etiology, pathogenesis, and clinical manifestations
Erythrocytosis is an increase in red blood cell mass, resulting in elevated hemoglobin and hematocrit levels.
Etiology
- Primary erythrocytosis
- Polycythemia vera (see below).
- Secondary erythrocytosis
- Due to increased erythropoietin (EPO) production:
- Chronic hypoxia:
- High altitude.
- Chronic obstructive pulmonary disease (COPD).
- Cyanotic congenital heart disease.
- Ectopic EPO production:
- Renal cell carcinoma.
- Hepatocellular carcinoma.
- Cerebellar hemangioblastoma.
- Relative erythrocytosis
- Hemoconcentration due to plasma volume loss:
- Severe dehydration.
- Burns.
Pathogenesis
- Increased EPO or RBC mass → increased blood viscosity → impaired microcirculation.
- Risk of thrombosis and vascular complications.
- Clinical manifestations
- Ruddy (plethoric) complexion.
- Headache, dizziness.
- Visual disturbances.
- Hypertension.
- Thrombosis risk: stroke, myocardial infarction.
- Pruritus (especially after hot bath — mostly in polycythemia vera).
Polycythemia rubra vera (polycythemia vera, PV)
A chronic myeloproliferative neoplasm characterized by clonal proliferation of erythroid precursors, leading to increased red cell mass, often also involving leukocytosis and thrombocytosis.
- Etiology
- Somatic mutation in JAK2 gene (JAK2 V617F mutation) in ~95% of cases.
- Independent of erythropoietin levels (EPO levels typically low).
- Pathogenesis
- JAK2 mutation → constitutive activation of JAK-STAT signaling → increased erythroid precursor proliferation in bone marrow.
- Increased RBC mass → hyperviscosity → sluggish blood flow and thrombosis.
- Possible progression to "spent phase" with bone marrow fibrosis or acute leukemia.
Clinical manifestations
- General
- Plethoric (red) face.
- Cyanosis (due to slow-flowing, deoxygenated blood).
- Neurological
- Headache.
- Dizziness.
- Visual disturbances.
- Tinnitus.
- Vascular
- Hypertension.
- Thrombotic events: deep vein thrombosis, stroke, myocardial infarction.
- Budd-Chiari syndrome (hepatic vein thrombosis).
- Skin
- Pruritus after warm bath or shower (aquagenic pruritus).
- Gastrointestinal
- Peptic ulcer disease (due to increased histamine release).
- Splenomegaly
- Due to extramedullary hematopoiesis.
Summary table