I.                   Polycythemia Vera (PV)

a.       Epidemiology

                                                              i.      Median age of onset: 71 years old

                                                            ii.      Approx. 2.2 new cases/100,000 pop per year.

b.      Pathophysiology:

                                                              i.      JAK2 V617F mutation in ~100% of PV patients.

                                                            ii.      MPL mutation (rare)

c.       Symptoms:

                                                              i.      Splenomegaly

                                                            ii.      Thrombocytosis and/or leukocytosis

                                                          iii.      Thrombotic complications

1.      PV should be suspected in cases of splanchnic thrombosis and in pts < 45 years of age with any unprovoked thrombosis

                                                          iv.      Erythromelalgia

                                                            v.      Aquagenic pruritis: itching following a warm bath or shower

d.      'Diagnostic criteria

                                                              i.      '↑ Red cell volume:

1.      'Females: Hb: > 16.5 g/dL, Hct: >50%

2.      'Males: Hb > 18.5 g/dL, Hct: >56%

                                                            ii.      Presence of JAK2 mutation, rarely MPL mutation

                                                          iii.      Minor criteria:


1.      Bone marrow: hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation

'2.      '↓ Serum EPO level below normal

a.      '↑↑RBCs d/t overactive stem cells → kidneys → ↓ EPO

3.      Growth factor ind. Erythroid colony growth in vitro

4.      Red flushing of face

                                                          iv.      Differential diagnoses

1.      Reactive or secondary polycythemia causes: hypoxia, familial polycythemia disorder (cardiac shunt), high affinity hemoglobin, truncated EPO receptor, illicit injection of EPO, EPO production by tumor

2.      Bled down or masked PV: patients meet other criteria for PV but do not have elevated Hb or HCT because of concomitant active bleeding, portal hypertension, hypersplenism or increased plasma volume.

e.       Prognosis, complications, treatments

                                                              i.      Median survival of untreated PV: 6-18 mos at time of diagnosis

                                                            ii.      Treatment is essential for maximizing outcomes

                                                          iii.      'Median overall survival is based on risk score: age, WBC count, history of venous thrombosis.

1.      > 67 yrs: 5 pts, 57 to 66: 2 pts

2.      WBC >15000/uL = 1 point

3.      History of venous thrombosis = 1 point

4.      ↓ survival with high risk

                                                          iv.      Common causes of death

1.      Thrombosis 29%

2.      Hematological malignancies 23%

3.      Nonhematologic malignancies 16%

4.      Hemorrhage 7%

5.      Post PV Myelofibrosis 3%

f.       Treatment

                                                              i.      Supportive care for pruritis and gout

                                                            ii.      Phlebotomy: in low risk (age <60 and no prior thrombosis, goal is hematocrit less than 45% in men and less than 42% in women). Should be combined with cytoreductive therapy

                                                          iii.      Cytoreductive therapy:

1.      Anagrelide

2.      Aspirin: in absence of acquired VWF disorder, ↓ combined risk of thrombosis

3.      Ruxolitinib: shown clinical benefit for spleen reduction, symptom reduction, and reduced phlebotomy requirements

                                                          iv.      'Pregnancy: keep Hct < 45%

1.      Continue low dose aspirin through pregnancy

2.      Use interferon