84 Essential Thrombocythemia

Question 1

TRUE OR FALSE

The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.

Answer 1

TRUE

The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.

Question 2

Mutation present in the majority of JAK2/MPL–wild-type patients

Answer 2

Calreticulin gene (CALR)

Question 3

A JAK2V617F mutation is found in approximately _____ of patients with ET.

Answer 3

50%

Question 4

A key endoplasmic reticulum protein with calcium-buffering and protein chaperone activity.

Answer 4

Calreticulin

Question 5

Approximately ____% of ET patients have a mild degree of palpable splenomegaly at diagnosis

Answer 5

10%

Question 6

Major source of morbidity and mortality in ET

Answer 6

THROMBOSIS

Question 7

A distinct clinicopathologic syndrome caused by occlusion of small blood vessels, manifests as discomfort and burning sensations in the fingers or toes, sometimes accompanied by mottling or discoloration of the skin.

Answer 7

Erythromelalgia

Question 8

The strongest predictive factors for thrombotic complications

Answer 8

Age greater than 60 years
A history of previous thrombosis

Question 9

The presence of this mutation is associated with a lesser risk of thrombosis or disease progression.

Answer 9

CALR

Question 10

TRUE OR FALSE

Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.

Answer 10

TRUE

Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.

Question 11

TRUE OR FALSE

The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.

Answer 11

TRUE

The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.

Question 12

Levels of thrombopoietin are (decrease, normal or elevated) in ET and have no diagnostic utility.

Answer 12

Normal or slightly elevated

Question 13

The marrow aspirate in ET often shows

Answer 13

Large, hyperlobulated megakaryocytes

Question 14

Mutation that shows hypocellular marrow in BMA

Answer 14

C-MPL

Question 15

A secondary increase in platelet count, initiated by cytokines such as _________

Answer 15

Interleukin-6

Question 16

Familial thrombocytosis is a rare disorder caused by mutations in ____________, _____________ or other unknown genes.

Answer 16

THPO (thrombopoietin gene)
C-MPL

Question 17

Characteristics of patients with CML present with an isolated thrombocytosis

Answer 17

Often female
With absent or minimal splenomegaly
A normal or marginally elevated white cell count
Usually without basophilia or circulating myeloid progenitors.

Question 18

TRUE OR FALSE

Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.

Answer 18

TRUE

Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.

Question 19

MDS with associated thrombocytosis

Answer 19

Isolated deletion of chromosome 5q (“5q-minus syndrome”)

Refractory anemia, with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T)

Question 19

TRUE OR FALSE

Karyotypic abnormalities are present in up to 50% of ET patients compared with only approximately 5% of patients with PMF, indicating a greater degree of genetic instability.

Answer 19

FALSE

Karyotypic abnormalities are present in up to 50% of myelofibrosis patients compared with only approximately 5% of patients with ET, indicating a greater degree of genetic instability.

Question 20

TRUE OR FALSE

In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.

Answer 20

TRUE

In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.

Question 21

Drug that is recommended for nearly all ET patients unless contraindicated and is possibly not needed in patients with the lowest risk profile (eg, patients with CALR mutations and no other risk factors)

Answer 21

Aspirin

Question 22

Drug used as first-line therapy for patients requiring treatment, and is the only cytoreductive agent proven to reduce thrombotic events

Answer 22

Hydroxyurea

Question 23

Major complications of Hydroxyurea

Answer 23

Reversible myelosuppression
Ulceration of the buccal mucosa or lower leg

Question 24

Major complications of Hydroxyurea

Answer 24

Reversible myelosuppression
Ulceration of the buccal mucosa or lower leg

Question 25

Drugs only recommended in patients older than 75 years of age

Answer 25

Pipobroman
Busulfan
Radioactive Phosphorus

Question 26

A quinazoline derivative, reduces the platelet count by inhibition of megakaryocyte differentiation

Answer 26

Anagrelide

Question 27

Because this agent is free from leukemogenic or teratogenic effects, it is often used for younger patients or during conception and pregnancy.

Answer 27

Recombinant interferon-α

Question 28

Drugs thar are effective at controlling the platelet count but are associated with an increased risk of progression to acute leukemia, particularly when used sequentially with hydroxyurea

Answer 28

Radioactive (32P) phosphorus

Alkylating agents such as busulfan

**Both 32P and busulfan can be given intermittently, with long intervals between doses, and may be useful in treating older patients who are unable to visit the clinic on a regular basis.

Question 29

Treatment for each type of ET

Very-low-risk:
Low-risk:
Intermediate-risk:
High-risk:

Answer 29

Very-low-risk: observation alone or, at most, Low-dose:aspirin therapy
Low-risk: once- or twice-per-day aspirin
Intermediate-risk: aspirin and hydroxyurea
High-risk: hydroxyurea and either twice-daily aspirin (arterial thrombosis) or hydroxyurea and systemic anticoagulation (eg, low-dose heparin or a direct thrombin inhibitor)

Question 30

The three risk factors for classification of ET

Answer 30

History of thrombosis
Age greater than 60 years
Presence of either a JAK2 or C-MPL mutation

Question 31

Thromboprophylaxis appears to be safe during pregnancy (eg, with low doses of low-molecular-weight heparin) and may be considered for patients with a history of thrombosis or pregnancy loss; in those with prior thrombosis, treatment should be continued for _______________postpartum

Answer 31

6 weeks

Question 32

Factors independently associated with decreased overall survival in ET

Answer 32

History of prior thrombosis
Anemia
Leukocytosis

** Additional factors with an increased risk of thrombosis - Predisposition to atherosclerotic diseases (diabetes, hypertension, hypercholesterolemia, or tobacco use)
Presence of a JAK2V617F or C-MPL mutation or increased marrow fibrosis at diagnosis

Question 33

Obstetric complications in ET are more prominent in those with_______________disease

Answer 33

JAK2V617F-positive

Question 34

The agent of choice for patients with high-risk disease should cytoreductive therapy be required during pregnancy

Answer 34

Interferon-α

Question 35

TRUE OR FALSE

Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.

Answer 35

TRUE

Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.

Question 36

Factors associated with an increased risk of thrombosis

Answer 36

Predisposition to atherosclerotic diseases (diabetes, hypertension, hypercholesterolemia, or tobacco use)
JAK2V617F or C-MPL mutation
Increased marrow fibrosis at diagnosis

Question 37

Considered to mandate cytoreductive therapy in ET patients

Answer 37

Age older than 60 years or
History of previous thrombosis