Polycythemia vera

Polycythemia vera is a myeloproliferative disorder associated with a Janus kinase-2 (JAK2) mutation that causes the neoplastic proliferation of mature myeloid cells, especially RBC.

Clinical features:-
1. Hyperviscosity symptoms (due to erythrocytosis) include headache, dizziness, tinnitus, and blurred vision.
2. Thrombosis (due to thrombocytosis) includes Budd Chairi syndrome, erythromelalgia (intense burning, pain and erythema of extremities due to microvascular ischemia), DVT, MI and stroke.
3. Bleeding (due to abnormal platelet function) manifests as easy bruising, epistaxis, GI bleeding.
4. Pruritus after hot water exposure (i.e. aquagenic pruritus) is due to histamine release from the basophils.
5. Hyperuricemia (due to increased cell turnover i.e. tumor lysis syndrome).
6. Splenomegaly 

Diagnosis:-
1.  Hb >18.5 g/dL or HCT >49% in men and Hb >16.5 g/dL or HCT >48% in women, or ↑ red cell mass.
2. Bone marrow biopsy shows hypercellularity marrow (i.e. erythroid, granulocytic and megakaryocytic proliferation).
3. Serum erythropoietin level is below the reference range for normal.
4. F.I.S.H demonstrates JAK-2 mutation is the investigation of choice.

WHO criteria for polycythemia vera 
Major Criteria 
1. Elevated red blood cell mass or hematocrit (high hemoglobin levels)
Hemoglobin (Hb): >18.5 g/dL in men and  >16.5 g/dL in women. 
Hematocrit (Hct):  >49% in men and  >48% in women. 
2. JAK2 V617F mutation or JAK2 exon 12 mutation.
3. Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation.
Minor Criteria
1. Low serum erythropoietin (EPO) levels.
2. Endogenous erythroid colony formation in vitro.
Diagnosis of polycythemia vera includes all 3 major criteria, or 2 major criteria and at least 1 minor criterion.

Treatment:-
1. Phlebotomy till hematocrit is <45% in men and <42% in women.
2. Low dose aspirin (reduces thrombosis), allopurinol (for hyperuricemia) and antihistamines (for pruritus).
3. Hydroxyurea (inhibits the production of RBCs and platelets).
4. JAK-2 inhibitors (e.g. ruxolitinib) if refractory to or intolerant of hydroxyurea.

Complications:-
1. DVT, MI and stroke (due to increased risk of thrombosis).
2. Progression to myelofibrosis, acute leukemia (i.e. AML).