8: Myeloproliferative disorders

Question 1

What is the myeloid lineage?

Answer 1

Granulocyte

Red blood cell

Platelet

lineages

Question 2

What is the difference between chronic myeloid leukaemia and acute myeloid leukaemia?

Answer 2

Differentiation and maturation PRESERVED in chronic disease

Question 3

Which mutation is associated with chronic myeloid leukaemia?

Answer 3

Philadelphia chromosome

Question 4

CML is BCR-ABL1 (positive / negative).

Answer 4

CML = BCR-ABL1 positive

Question 5

What is a normal, secondary cause for a rise in blood components?

Answer 5

Reactive change

in response to infection usually

Question 6

Which blood components can increase in myeloproliferative disorders?

Answer 6

RBCs

Platelets

White cells (basophils/eosinophils is especially significant)

Question 7

Which organ can enlarge in myeloproliferative disorders?

Answer 7

Spleen

Increased cell breakdown

Question 8

What is a risk seen in hyperviscosity secondary to raised cell counts?

Answer 8

Thrombosis

Question 9

Chronic ___ causes a secondary polycythaemia - why?

Answer 9

Chronic hypoxia (e.g sleep apnoea, COPD)

Persistent EPO release by the kidneys

Question 10

What is the course of untreated chronic myeloid leukaemia?

Answer 10

1. Chronic phase for 3-5 years, maturation intact

2. Accelerated phase - maturation starting to fail

3. Blast crisis and death - more closely resembling an acute leukaemia

Question 11

What are some clinical features of CML?

Answer 11

Hyperviscosity symptoms

Hypermetabolism - cachexia

Splenomegaly

Gout

Question 12

How is suspected CML investigated?

Answer 12

FBC

Bone marrow biopsy

Question 13

An increase in which specific blood components strongly suggest CML?

Answer 13

Eosinophilia

Basophilia

not normally found in large numbers

Question 14

What might be misdiagnosed as CML based on blood changes?

Answer 14

Reactive changes due to infection

Question 15

Which genetic mutation is commonly found in CML?

Answer 15

Unbalanced chromosome 22 translocation

‘BCR-ABL’ gene on the Philadelphia chromosome

Question 16

BCR-ABL mutations on the Philadelphia chromosome affect which protein?

Answer 16

Tyrosine kinase

Question 17

What is a tyrosine kinase inhibitor used to treat CML?

Answer 17

Imatinib

Question 18

Imatinib is a ___ ___ inhibitor which massively increases life expectancy in which disease?

Answer 18

tyrosine kinase inhibitor

CML

Question 19

CML is positive for which mutation?

Answer 19

BCR-ABL1

Philadelphia chromosome (22)

Question 20

What is erythromelalgia?

Which group of diseases is it a feature of?

Answer 20

Hot, swollen, red, painful digits due to blood stasis

Myeloproliferative diseases

Caused by HYPERVISCOSITY of blood

Question 21

In which disease does haemoglobin and haematocrit increase abnormally?

Answer 21

Polycythaemia

Question 22

What is primary polycythaemia called?

Answer 22

Polycythaemia rubra vera

Question 23

Which genetic mutation is implicated in polycythaemia rubra vera?

Answer 23

JAK2

Question 24

What causes secondary polycythaemia?

Answer 24

Chronic hypoxia

EPO-secreting renal tumours

Question 25

What is **pseudopolycythaemia**?

Answer 25

**Appearance of raised Hb / haematocrit which is actually due to a reduced plasma volume**

Question 26

What causes **pseudopolycythaemia**?

Answer 26

**Dehydration / Diuretic therapy** **Obesity** **Alcohol excess**

Question 27

**Pseudopolycythaemia and** ___ **polycythaemia** mean the same thing.

Answer 27

**apparent polycythaemia**

Question 28

What are some **symptoms** of **primary polycythaemia**?

Answer 28

**Plethora** **Itch** (caused by warm water) **Hyperviscosity symptoms**

Question 29

Which genetic mutation is screened for in **polycythaemia rubra vera?**

Answer 29

**JAK2**

Question 30

**JAK2 mutations** are seen in **95% of patients** with ___ \_\_\_ \_\_\_.

Answer 30

**polycythaemia rubra vera** (primary)

Question 31

What process is **uninhibited** it patients with **polycythaemia rubra vera?**

Answer 31

**Erythropoiesis**

Question 32

What are some investigations for suspected **secondary polycythaemia**?

Answer 32

**CXR** **Medication history** - e.g testosterone **EPO levels** **Bone marrow biopsy**

Question 33

How is **polycythaemia rubra vera** treated?

Answer 33

**Venesection** until haematocrit is \< 0.45 **Aspirin** (anti-platelet - deactivates platelets, reducing hyperviscosity of blood) **Cytotoxic drugs** e.g hydroxycarbamide - kills off excess cells

Question 34

**Polycythaemia rubra vera** can lead to **thrombosis** in some patients. How is this prevented?

Answer 34

**Aspirin**

Question 35

In addition to **venesection**, how can Hb / haematocrit be reduced in polycythaemia rubra vera?

Answer 35

**Cytotoxic drugs** e.g hydroxycarbamide

Question 36

In which disease is **idiopathic platelet excess** seen?

Answer 36

**Essential thrombocythaemia**

Question 37

**Essential thrombocythaemia** can cause both **thrombosis** and **abnormal bleeding**. Why?

Answer 37

**Thrombosis** - excess of platelets **Abnormal bleeding** - platelets mop up vWF, causing acquired von Willebrand's disease

Question 38

Is **anaemia** a feature of **essential thromocythaemia**?

Answer 38

**No** Don't confuse ET for thrombocytosis caused by reactive change, in which patient would be anaemia

Question 39

**RBCs** and **platelets** are derived from the same progenitor cells. What are some causes of **reactive thrombocytosis** which may cause a blood picture similar to **essential thrombocythaemia?**

Answer 39

**Blood loss** **Haemolysis** **Inflammation** **Malignancy**

Question 40

How is **essential thrombocythaemia** treated?

Answer 40

**Aspirin** (anti-platelet drug) **Chemotherapy** to suppress proliferation in some patients

Question 41

Which **myeloproliferative disorder** causes **progressive fibrosis** of the bone marrow?

Answer 41

**Myelofibrosis**

Question 42

**Myelofibrosis** can occur secondary to which other MPDs?

Answer 42

**Polycythaemia** **Essential thrombocythaemia**

Question 43

What **blood film** appearance, caused by leakage of progenitor cells into the blood, is seen in **myelofibrosis**?

Answer 43

**Leukoerythroblastic blood film**

Question 44

Which shape of RBC is seen in **myelofibrosis?**

Answer 44

**Teardrop cells**

Question 45

What are the main **clinical features** of **myelofibrosis**?

Answer 45

**Pancytopaenia** - anaemia, abnormal bleeding, increased infection risk **Splenomegaly** **Hypercatabolism** - cachexia **Teardrop cells** on a blood film

Question 46

What are the two **blood film** appearances to look out for in **myelofibrosis**?

Answer 46

**Leukoerythroblastic film** **Teardrop cells**

Question 47

What are some **causes** of a **leukoerythroblastic blood film**?

Answer 47

**Reactive change** as in infection ## Footnote **Bone marrow infiltration** **Myelofibrosis**

Question 48

What is the appearance of **myelofibrosis** on a bone marrow biopsy?

Answer 48

**Fibrosis** - collagen fibres

Question 49

How is **myelofibrosis** treated?

Answer 49

**Supportive management of pancytopaenia** (blood transfusion, platelet transfusion, prophylactic antibiotics) ## Footnote **Young, fit patients receive stem cell transplants**

Question 50

**Most raised blood counts** will be caused by ___ change.

Answer 50

**reactive change** infection

Question 51

Which **supplement**, often taken by bodybuilders, can cause **secondary polycythaemia**?

Answer 51

**Testosterone**

Question 52

Patients with **polycythaemia rubra vera** have blood taken until their **haematocrit** is below which threshold?

Answer 52

**\< 0.45** 0.45 means that 45% of your blood sample is made up of red cells