Lecture 5 MPD - Polycythemia Vera

Question 1

What does polycythemia vera mean?

Answer 1

vera –> “true”
polycythemia –> increase in all cell lines.

Question 2

What conditions can cause polycythemia that are different from Polycythemia Vera?

Answer 2

Different from PV are:
1. Secondary Polycythemia (refers to conditions of compensatory erythrocytosis related to tissue hypoxia).
2. Relative Polycythemia (caused by an increased Hematocrit due to decreased plasma volume by conditions such as dehydration).

Question 3

What is secondary polycythemia?

Answer 3

Secondary Polycythemia:
Condition of compensatory erythrocytosis related to tissue hypoxia.

Such as
1)cardiovascular and pulmonary disease,
2)abnormal hemoglobins with increased oxygen affinity
3) heavy smoking and
4) kidney disease (renal tumors). This condition associated with increased red cell mass and increased erythropoietin levels.

Question 4

What relative polycythemia?

Answer 4

Relative Polycythemia:
Increased hematocrit due to decreased plasma volume.
In conditions such as dehydration from severe burns, vomiting, severe diarrhea, lack of water.

Question 5

What are the symptoms of Polycythemia Vera?

Answer 5

Polycythemia Vera:
These symptoms are due to increased blood volume, increased viscosity, & increased blood pressure:
1. Headache, dizziness
2. Dyspnea (difficult breathing)
3. Peripheral cyanosis (low O2 & increased CO2 causing bluish & grayish discoloration to skin)
4. Gastric ulcers
5. Ringing in ears
6. Blurred vision

Patient’s also can have:
1. Gout (from increased uric acid from large cell turnover)
2. Itching of eyes and skin (likely due to histamine release from increase in basophils)
3. Hepatomegaly & splenomegaly (extramedullary hematopoiesis)
4. Thombosis (due to increased platelet count & slowed blood flow)
5. Bleeding (due to increased blood pressure and abnormal platelets)

Question 6

What is the main cell affected by Polycythemia Vera?

Answer 6

Erythrocytes

Question 7

What are the peripheral blood findings of polycythemia vera?

Answer 7

PV Blood findings:
1. RBC, Hgb and Hct all increased
2. RBCs may be microcytic, hypochromic (iron def.)
3. Retic count not significantly elevated
4. LAP score usually increased.
5. Platelet counts usually increased with very high counts possible. Large & giant form of platelets may be present.
6. WBC counts typically elevated w/ left shift.
7. Absolute neutrophilia w/ slight basophilia and eosinophilia. Few myelocytes, metamyelocytes and occ’l NRBC may be present.

Question 8

What are bone marrow findings for PV?

Answer 8

Bone Marrow Findings for PV:
1. Bone marrow hypercellular w/ fat spaces almost completely replaced.
2. Increased normoblasts (RBC precursor cells)
3. Megakaryocytes present.
4. Fibrosis of marrow worsens with progression of disease.

Question 9

What are chemistry findings for Polycythemia Vera?

Answer 9

Polycythemia Vera Chemistry Findings:
1. N to increased levels of serum B12.
2. Increased serum B12 binding capacity.
3. Decreased serum iron and ferritin.
4. Serum erythropoietin levels decreased.
5. Increased uric acid causing gout (in some cases).

Question 10

What are important diagnostic tests for PV?

Answer 10

1. Red Cell Mass - distinguishes between relative & absolute erythrocytosis
2. Oxygen saturation - important test because O2 saturation normal in PV and decreased in secondary polycythemia.
3. Erythropoietin levels - important because decreased in PV but increased in secondary.

Question 11

What is Polycythemia Vera?

Answer 11

Abnormal pluripotent stem cell defect (myeloproliferative disorder) which proliferates in abnormally large numbers of mainly erythroid but also granulocytic and megakaryocytic cells.

True increase in Red Cell Mass with RBC> 5.9 in women and >6.6 in men.

Mild granulocytic leukocytosis and thrombocytosis occur frequently.

Question 12

Why might the RBC morphology be microcytic and hypochromic in Polycythemia Vera?

Answer 12

Due to iron deficiency from chronic bleeding, therapeutic phlebotomy and increased RBC production and turnover.

Question 13

Why is fibrosis of the marrow believe to worsen with progression of the disease of PV?

Answer 13

Fibrosis thought to be caused by platelet derived growth factor (PDGF) secreted by granules of megakaryocytes.

Question 14

Why is Serum Vitamin B12 binding capacity increased in Polycythemia Vera?

Answer 14

Serum Vitamin B12 binding capacity increased due to increased production of transcobalamin I by increased number of neutrophils.

Question 15

What is the result of increased cell turnover in PV?

Answer 15

Increased uric acid causing gout in some cases.

Question 16

What is the importance of the Red Cell Mass test for Polycythemia Vera?

Answer 16

Red Cell Mass distinguishes between relative and absolute erythrocytosis (primary and secondary).

Question 17

How does one perform and interpret a Red Cell Mass test?

Answer 17

Take blood sample from patient and label with radioactive material and inject back into patient. Wait 15 mins and take another blood sample and measure radioactivity.

Increased radioactivity means increased Red Cell Mass (RCM).
Decreased radioactivity means increased blood volume.

Question 18

What levels of Red Cell Mass are indicative of PV?

Answer 18

RCM >36ml/kg in males and >32m./kg in females is indicative of PV.

Question 19

What gene is mutated in 90% to 97% of Polycythemia Vera patients?

Answer 19

JAK2 gene

Mutation un-regulates the control of RBC production by erythropoietin.
Resulting in uncontrolled proliferation of RBCs.

Question 20

What are the treatments for Polycythemia Vera patients?

Answer 20

Usually combination of phlebotomy, radioactive phosphorus, myelosuppressive drugs or combination thereof.

Continue phlebotomy worsens iron deficiency. This is a desired state as it limits progress of this disease.

Question 21

What are the risks for patients being treated with radioactive phosphorus and myelosuppressive drugs?

Answer 21

Can transform the disease to acute leukemia.
Hydroxyurea less leukomogenic and effective therefore is drug of choice.

Question 22

What does the appearance of tear drop cells may indicate in a patient with PV?

Answer 22

Tear drops cells demonstrates the most common transition of PV to AMM (Agnogenic myeloid metaplasia), also called the spent phase.

Hepatosplenomegaly becomes more severe in this stage.
PB shows increased NRBCs w/ left shift to very immature cells w/ possible blast cells present.

Poor prognosis at this stage with hemorrhage and infection usual cause of morbidity.

Question 23

What other conditions besides AMM, do patients with PV transform? Why is this thought to occur?

Answer 23

Significant number of patients with PV transform to AML and few to ALL.

Chemotherapy drugs may contribute to this transformation.