Myeloproliferative disorders

Question 1

What is Myeloproliferative?

Answer 1

Overproduction of cells in the bone marrow

Question 2

There are four main myeloproliferative disorders. What are they?

Answer 2

Chronic myelogenous leukemia (CML)
Polycythemia vera
Myelofibrosis
Essential thrombocytosis

Question 3

What is polycythemia vera is characterized by what?

2

Answer 3

elevated Hgb/HCT.

Elevated red cell mass (although difficult to measure)
Elevated hemoglobin and hematocrit

Question 4

There are 3 main causes of polycythemia in general. (elevated HgB and HCT)
What are they?

Answer 4

Appropriately elevated erythropoietin: hypoxemia

Inappropriately elevated erythropoietin: renal cell carcinoma, hepatocellular carcinoma

Germline and somatic mutation: polycythemia vera

Genetic production
Renal production
something wrong with erythropoeitn production

Question 5

Survival if untreated?

treated?

Answer 5

untreated is 6-18 months

If treated the survival is > 10 years

Question 6

Symptoms associated with polycythemia?

Answer 6

Headache
Weakness
Dizziness
Excessive sweating

Question 7

Demigraphic that usually gets polycythemia?

3

Answer 7

Average age at diagnosis is 60 years of age
Men more common then women
Most common is in men aged 70-79 (24 cases per 100,000)

Question 8

Hallmark symptoms of polycythemia?

2

Answer 8

Pruritus post bathing is a hallmark symptom

Erythromelalgia: burning pain in the feet and/or hands often with pallor, erythema or cyanosis

These with all the symtpoms described before

Question 9

What are the symptoms of polycythemia related to?

Answer 9

thrombosis

Arterial and venous

Question 10

Transient visual disturbances assocaited with thrombosis due to polycythemia?
2

Answer 10

Amaurosis fugax
Scintillating scotomata (opthlamic migraine, decreased retinal and choroidal blood flow due to increased blood viscosity

Question 11

GI symtpoms associated with polycythemia?

3

Answer 11

Epigastric discomfort
History of peptic ulcer disease
Gastroduodenal erosions

Question 12

Physical exam findings in polycythemia vera?

6

Answer 12

1. Splenomegaly 70% of the time
2. Facial plethora (ruddy cyanosis) 67%
3. Hepatomegaly
4. Injection of conjunctival small vessels &/or engorged veins of the optic fundus
5. Excoriation of the skin
6. Gouty arthritis and tophi

Question 13

Lab abnormalities in polycythemia vera?

9

Answer 13

1. Hgb/HCT > 18.5/56 men
2. Hgb/HCT > 16.5/50 women
3. WBC > 10.5
4. Platelets > 450 K
5. Elevated serum lactate dehydrogenase (LDH is released when cells or tissue is destroyed) in 50%
6. JAK2 mutation in 98%
7. Abnormal serum erythropoietin in 81% (abnormally low)
8. Hypercellular bone marrow
9. Iron storage in bone marrow is absent

Question 14

Criteria for PV?

2

Answer 14

Hemoglobin > 18.5 g/dL in men and 16.5 g/dL

Jak2 mutation

Question 15

What is polycythemia vera treatment targeted at?
2

In which ways can we do this?
3

Answer 15

Lowering hemocrit and decreasing thrombosis

Phlebotomy to keep HCT

Question 16

What are the mylosuppressive agents that can be used in the treatment of polycythemia vera and in what situations are they used?

Answer 16

1 . Hydroxyurea- use if other treatments arent working or if at high risk for thrombosis
2. Interferon alpha- Use in womenin childbearing age or in hydroxyurea is ineffeective

Question 17

What are the symptoms of PV?

Answer 17

Pruitis
Hyperuricemia
Erythromelalgia

Question 18

How would we treat pruitis caused by PV?

7

Answer 18

1. Antihistamines,
2. H2 blockers,
3. myelosuppression,
4. interferon alpha,
5. antidepressants such as paroxetine (Paxil) or fluoxetine (Prozac),
6. photo chemotherapy
7. (cool water. hotter the water the worse it will be)

Question 19

How would we treat hyperuricemia (gout) caused by PV?

Answer 19

Allopurinol for prevention

Question 20

How would we treat erythromelalgia caused by PV?

2

Answer 20

1. Aspirin 75-100 mg daily

2. Lowering the platelet count with myelosuppresive agents also helps

Question 21

Polycythemia vera can progress to more serious disorders of bone marrow metabolism such as?
2

Answer 21

Myelofibrosis

Acute leukemia

Question 22

What is the pathology behind myelofibrosis?

What causes it?

Answer 22

Replacement of the marrow with collagenous connective tissue

Cause is generally unknown but it is associated with spent phase of polycythemia

Question 23

What are the main causes of morbidity and mortality in myelofibrosis?
5

Answer 23

Progression to acute leukemia
Infection
Bleeding
Portal hypertension
Vascular complications

Question 24

What are the most common clinical presentations of myelofibrosis? 2

What are other common manifestations seen in myelofibrosis? 5

Answer 24

severe fatigue
LUQ pain
(due to splenomegaly)

1. Symptoms due to splenomegaly (25-50%)
   - -LUQ pain (could radiate to left shoulder)
   - -Early satiety (gastric vessels plugged up)
2. Hepatomegaly
3. Weight loss (5-20%)
4. Low grade fever, night sweats (5-20%)
5. Asymptomatic (15-30%)

Question 25

What are symptoms of myelofibrosis due to hepatomegaly? | 5

Answer 25

1. Ascites, 2. esophageal and gastric varices, 3. GI bleeding, 4. hepatic encephalopathy, 5. portal vein thrombosis

Question 26

What is extramedullary hemotopoiesis and why is it problematic?

Answer 26

When red cell production is pushed outside the bone marrow and into the surrounding tissue by the medullary tissue turning into connective tissue. It will then disrupt the tissue of that organ that it invades.

Question 27

What can extramedullary hematopoiesis present as? (where does it go commonly) 9

Answer 27

1. splenomegaly, 2. hepatomegaly, 3. lymphadenopathy, 4. pleural effusions, 5. pericardial effusions, 6. abdominal effusions, 7. GI, 8. GU (dysuria) or 9. Respiratory (dyspnea)

Question 28

What will a blood smear look like in someone with myelofibrosis? 2

Answer 28

1. Marked poikilocytosis (variation in cell shape) - Especially with the tear-drop poikilocytes 2. Anisocytosis

Question 29

What will a bone marrow biopsy in the early stages of PMF result in? 2 What happens has the disease progresses?

Answer 29

1. high white count with a left shift, and a 2. hypercellular marrow, - - features common to all myeloproliferative disorders the marrow becomes replaced by fibrous tissue.

Question 30

In PMF what will the WBC look like?

Answer 30

WBC can be low or high > 30,000 in 11%; or low in 8% (depending on stage of disease)

Question 31

In PMF what will platelet levels look like?

Answer 31

Platelets can be low or high > 500,000 in 13%; or low in 26% (depending on stage of the disease)

Question 32

What lab levels will be elevated in PMF? | 4

Answer 32

Elevated alkaline phosphatase Elevated lactate dehydrogenase Elevated uric acid Vitamin B12

Question 33

Why is alkaline phophatase elevated in PMF?

Answer 33

Due to liver involvement or bone disease

Question 34

Why is lactate dehydrogenase Elevated in PMF?

Answer 34

Due to ineffective hematopoiesis

Question 35

Why is uric acid elevated in PMF?

Answer 35

Due to enhanced turnover of hematopoietic tissue

Question 36

Why is B12 elevated in PMF?

Answer 36

Due to increased neutrophil mass

Question 37

PMF pts might have a JAK2 mutation. What would this disrupt?

Answer 37

regulation of the production of cells in the bone marrow

Question 38

Characteristics of PMF that you need to know??? | 4

Answer 38

1. bone marrow fibrosis 2. philadelphia chromosome absence 3. Splenomegaly 4. Tear drop erythrocytes

Question 39

Treatment options for PMF? | 6

Answer 39

Pretty limited 1. Stem cell transplant 2. Hydroxyurea 3. Various chemotherapeutic agents 4. JAK2 inhibitors:Ruxolitinib (Jakafi) 5. Splenectomy but may cause worsening hepatomegaly and decline in liver function 6. Radiation therapy (spleen or other sites of EMH)- not to bone marrow but to the sites of extramedullary hematopoeisis

Question 40

What is essential thrombocytosis due to? | 2

Answer 40

1. overproduction of platelets (isolated thrombocytosis)- clotting disorder 2. Abnormal platelet function that can lead to thrombosis and bleeding- bleeding disorder

Question 41

How would we diagnose essential thrombocytosis?

Answer 41

elevated platelet count without other blood cell abnormalitites

Question 42

What would a peripheral smear show in a patient with essential thrombocytosis?

Answer 42

normal RBC morphology

Question 43

What would a bone marrow biopsy show in essential thrombcytosis?

Answer 43

reveals increase in number and giant megakaryocytes (platelets) but it otherwise normal

Question 44

HIGH FREQUENCY OF JACK MUTATIONS

Answer 44

STATEMENT

Question 45

Symptoms are secondary to elevated platelet count in essential thrombocytosis? 6

Answer 45

1. Headache 2. Lightheadedness 3. Visual changes 4. Numbness, tingling or burning in the feet (erythromelalgia) 5. Splenomegaly 6. History of thrombosis

Question 46

Where is arterial thrombosis most likely to occur? | 3

Answer 46

in the hands, feet and brain but can occur anywhere (heart, larger vessels)

Question 47

Where is venous thrombosis most likely to occur? | 4

Answer 47

mesenteric, hepatic and portal vein as well as deep vein thrombosis can occur

Question 48

What is the treatment targeted at for essential thrombocytosis? And what are the treatments? 2

Answer 48

lowering the platelet count to prevent symptoms and thrombosis. 1. Low dose aspirin (81 mg/day) 2. Hydroxyurea to keep platelet count below 500,000

Question 49

How can essential thrombocytosis progress to worse conditions? 4

Answer 49

Bone marrow may become fibrotic Massive splenomegaly may occur 10-15% risk of progression to myelofibrosis after 15 years 1-2% risk of progression to acute myelogenous leukemia over 20 years