Polycythemia vera is characterised by peripheral erythrocytosis. It is commonly caused by a point mutation in JAK2. Thrombocytosis and leukocytosis can also occur in addition to erythrocytosis. The classic presentation is an unexplained high haemoglobin with low MCV and low ferritin.
Phases of polycythemia vera
| Phase | Description |
|---|---|
| Prodrome | Borderline mild erythrocytosis |
| Overt polycythemia | Significantly increased red cell mass |
| Spent-phase | Bone marrow fibrosis causing cytopenias and hepatosplenomegaly.<10% progress to myelofibrosis. |
- Risk factors
- Genetic predisposition
- Ionizing radiation
- Occupational toxins
- Sites involved in polycythemia vera
- Peripheral blood
- Bone marrow
- Spleen and Liver – common sites of extramedullary hematopoiesis
- Pathophysiolgy
- Point mutation in the JAK2 gene at 9p24 → constitutional activation of STAT transcription factors → growth factor-independent proliferation and survival of RBCs (and platelets)
- Signs and symptoms
- Hyperviscosity syndromes:
- Headache, blurred vision, vertigo, tinnitus, dizziness
- Chest and abdominal pain (abdominal pain is due to ischemic bowel caused by thrombosis)
- Myalgia
- Weakness and Fatigue
- Budd-Chiari syndrome, Mesenteric vein thrombosis, Arterial thrombosis, Venous thrombosis
- Intermittent claudication
- Aquagenic pruritus (due to the release of histamine from basophils from contact with warm water)
- Erythromelalgia: Increased skin temperatures, burning sensation, and redness
- Early satiety (due to splenomegaly, especially in the spent phase)
- Gout
- Hyperviscosity syndromes:
- Investigations
- Complete Blood Count
- Hb: >16.5g/dL M, >16g/dL F
- Hct: >49% M, >48% F
- MCV: low despite high hemoglobin
- WBC: Leukocytosis <20k
- Platelets: modest thrombocytosis
- Peripheral blood film
- RBC: Normochromic normocytic RBC, Microcytic Hypochromic RBC with concomitant IDA, Erythrocytosis, Rare normoblasts
- Reticulocytes: Deeply basophilic reticulocytes
- Leukocytes: Mild Leukocytosis, Left-Shift, Mild Basophilia
- Platelets: Thrombocytosis (Prominent in prodromal and exaggerated by concurrent IDA),
- Spent-phase: Leukoerythroblastosis, Myeloid metaplasia, Poikilocytosis, >10% blasts in PBF
- Bone marrow aspirate or Trephine Biopsy
- Cellularity: Hypercellular, >80% cellularity
- Myeloid: Panmyelosis (Predominant erythroid and Megakaryocytes), complete and progressive maturation of all 3 hematopoietic lineages, abnormal megakaryocyte morphology and architecture (Variably hyperlobulated)
- Fibrosis: Reticulin fibrosis is minimal or absent
- Iron stores: Diminished, often absent
- Spent-phase: Overt bone marrow reticulin and collagen fibrosis, Prominent osteosclerosis, Increase in blasts (but <20%), dilated sinuses with intrasinusoidal hematopoiesis, decline in hematopoietic cells
- Cytogenetics
- Karyotype, FISH: JAK2 V617F or JAK2 exon 12 mutations
- Molecular studies
- PCR: JAK2 V617F or JAK2 exon 12 mutations
- Erythropoietin: Subnormal EPO (<4.1 mU/mL)
- Red Cell Mass: >25%
- Serum ferritin: low/normal
- Complete Blood Count
- Treatment
- Serial phlebotomy
- Low-dose aspirin
- Hydroxyurea as an adjunct for high-risk patients who fail phlebotomy
- Has a slightly increased risk of secondary leukaemia
- Ruxolitinib – a second-line TKI – for JAK2 mutations
- Phosphorus-32 therapy
- Complications
- Thrombotic complications
- Arterial thrombosis: Stroke, Peripheral arterial emboli, Myocardial Infarction, Splenic infarction
- Venous thrombosis: Budd-Chiari syndrome, Pulmonary embolism, Deep vein thrombosis, Splenic vein thrombosis, Portal vein obstruction, Mesenteric vein thrombosis, Renal vein thrombosis
- Hemorrhagic complications: Petechiae, Epistaxis, Bleeding gums
- Gout: High cell turnover resulting in elevated uric acid
- AML and Myelodysplastic syndrome: Additional genetic mutations cause transition to other hematologic diseases
- Post-polycythemia vera myelofibrosis (Spent): Reticulin fibrosis of the bone marrow
- Thrombotic complications