Chapter 131 Polycythemia Vera and Myeloproliferative Neoplasms

Question 1

Central role in the pathogenesis of PV?

Answer 1

Mutation of the tyrosine kinase JAK2

JAK2 - leads to EPO sensitivity, apoptosis resistance of erythroid progenitor cells

Question 2

Most often, PV is first recognized by what presenting manifestation?

Answer 2

Incidentally high Hgb and Hct

Other manifestations:

1. Isolated thrombocytosis (Inc Platelet)
2. Leucocytosis (Inc WBC)
3. Splenomegaly

Question 3

How does uncontrolled erythocytosis affect the blood?

Answer 3

Causes hyperviscosity

Question 4

What neurologic symptoms are caused by viscous blood from uncontrolled erythrocytosis?

Answer 4

Headache
Tinnitus, Vertigo
Visual disturbances
TIA

Question 5

What common vessels are involved in thrombosis caused by PV?

Answer 5

Cerebral
Cardiac
Mesenteric

Question 6

Obstruction of which vessel in young women may cause catastrophic?

Answer 6

Intraabdominal venous thrombosis

Sudden and complete obstruction of the hepatic vein - raises suspicion and will need workup for PV

Question 7

Erythema, burning, pain in the extremities is a symptom complex known as?

Answer 7

Erythromelalgia

Primarily involves the lower extremities
Associated with thrombocytosis
Etiology unknown
May sometimes present as digital infarction

Question 8

First line treatment if erythromelalgia occurs in patients with PV?

Answer 8

Salicylates

Question 9

Due to large turnover of hematopoietic cells, how does PV affect uric acid?

Answer 9

Causes hyperuricemia with secondary gout and uric acid stones

Question 10

Hemoconcentration secondary to dehydration, diuretics, ethanol, androgens and tobacco are considered: Absolute or Relative causes of erythrocytosis?

Answer 10

Relative Erythrocytosis

Question 11

In contrast to other true causes of erythrocytosis, what event in PV can mask the elevated red cell mass?

Answer 11

Expansion of the plasma volume

Therefore red cell mass and plasma volume determination is necessary to establish absolute vs relative erythrocytosis

Question 12

What syndrome causes relative erythrocytosis due to a reduction in plasma volume alone?

Answer 12

Gaisbock’s Syndrome

also known as stress or spurious erythrocytosis

Question 13

Only three situations cause microcytic erythrocytosis, namely:

Answer 13

1. Beta thalassemia trait
2. Hypoxic erythrocytosis
3. PV

Question 14

Differentiate beta thalassemia trait and PV in terms of RDW

Answer 14

Beta thalassemia - normal RDW

PV and Hypoxic - elevated RDW due to associated iron deficiency

Question 15

A bone marrow aspirate and biopsy is warranted for diagnosis of PV. T/F?

Answer 15

False.

No specific diagnostic information because these may be normal

Question 16

What assay supersedes all other tests for establishing the diagnosis of PV?

Answer 16

JAK2 V617F assay

Question 17

What symptom involving CNS can develop in patients with PV (can be a variant of erythromelalgia)?

Answer 17

Ocular migraine

Question 18

What GI disease is increased in incidence in patients with PV?

Answer 18

Peptic ulcer disease due to H pylori

Question 19

What is the most significant complication and often the presenting symptom of PV?

Answer 19

Thrombosis due to erythrocytosis

Question 20

What cut off level of Hgb and Hct in men and women are recommended for PV to avoid complications?

Answer 20

Male: Hgb = 140, Hct <0.45
Female: Hgb = 120, Hct <0.42

Question 21

What treatment for PV is needed to reduce hyperviscosity by bringing RBC mass into normal range?

Answer 21

Phlebotomy

Periodic phlebotomy needed to induce a state of iron deficiency that prevents accelerated reexpansion of red cell mass

Question 22

How often is phlebotomy needed once iron deficient state is achieved in patients with PV?

Answer 22

Every 3 months

Question 23

Treatment for thrombosis due to erythrocytosis?

Answer 23

Anticoagulants ONLY when thrombosis is already present

PT PTT may be falsely low or high due to red cell mass imbalance

Question 24

What drug may be given to avoid further elevation of uric acid when chemotherapy is used?

Answer 24

Allopurinol

Asymptomatic hyperuricemia (<10) does NOT require treatment

Question 25

What drug under investigation can be given for symptomatic splenomegaly?

Answer 25

Pegylated interferon gamma

Can also cause complete hematologic and molecular remissions in PV

Question 26

What phosphodiesterase inhibitor can reduce platelet count and preferred over hydroxyurea?

Answer 26

Anagrelide

Lacks marrow toxicity and protective against venous thrombosis

Question 27

If a cytotoxic agent is needed for PV, first line drug is:

Answer 27

Hydroxyurea

Used for as short a time as possible
Leukemogenic
Does NOT prevent thrombosis

Question 28

Non specific JAK2 Inhibitor can reduce spleen size and alleviate symptoms due to cytokine release?

Answer 28

Ruxolitinib