Polycythemia vera

Vignette says a 55 year old male presents to his primary care physician with chief complaints of persistent headaches and dizziness over the past few months; He also reports of episodic blurring of vision and burning sensation in hands and feet over the past few months; Interestingly, he also suggests of having generalized pruritus, especially after a hot shower; Vital signs show blood pressure of 140/90 mm of Hg, pulse rate of  80 bpm, respiratory rate of 16 breaths/min, oxygen saturation of 96% in RA and temperature of 98.7 F; Examination shows splenomegaly; Laboratory studies show hemoglobin of 20 mg/dl, hematocrit of 56%, WBC count of 18,000 cells/mm3 and platelet count of 5 lakhs/mm3; Serum erythropoietin level is low; Bone marrow biopsy shows hypercellular marrow with increased erythroid, granulocytic and megakaryocytic proliferation (i.e. panmyelosis); F.I.S.H  demonstrates JAK-2 mutation; Diagnosis?

Diagnosis is polycythemia vera.

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 and 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).