Polycythaemia & Myeloproliferative disorders

Question 1

Normal range of Hb

Answer 1

135-175

Question 2

What is pseudopolycythaemia

Answer 2

When cell plasma volume is decreased

Question 3

What is true polycythaemia

Answer 3

When red cell mass is increased

Question 4

What are the types of true polycthaemia

Answer 4

Primary- polycythemia vera reduced EPO

Secondary - increased EPO

Question 5

When is secondary polycythemia appropriate and inappropriate

Answer 5

Appropriate
•High altitude
•Hypoxic lung disease
•Cyanotic heart disease 
•High affinity haemoglobin

Inappropriate
• Renal disease(cysts,tumours inflammation)
• uterinemyoma
• other tumours (liver, lung)

Question 6

Types of myeloproliferative disorders

Answer 6

• Ph negative
– Polycythaemia vera (PV)
– Essential Thrombocythaemia (ET)
– Primary Myelofibrosis (PMF)

• Ph positive
– Chronic myeloid leukaemia (CML)

Question 7

Difference between MPD, MDS and leukaemia

Answer 7

MPN- proliferation and full differentiation
MDS- ineffectvie proliferation and differentiation
LK- Proliferation without differentiation

But there is overlap

Question 8

Symptoms of PV

Answer 8

o Symptoms of hyperviscosity
 Headaches, light-headedness, stroke
 Visual disturbances
 Fatigue, dyspnoea

o Increased histamine release
 Aquagenic pruritus (itch after a hot bath)
 Peptic ulceration

Question 9

Investigations for PV

Answer 9

Investigations:
High Hb				
High Hct 
High MCV 
High plasma volume

JAK2 V617F mutation (DIAGNOSTIC)

Question 10

Treatment of PV

Answer 10

Reduce viscosity and keep Hct < 45%
Venesection (but, bleeding and iron deficiency stimulates megakaryocytes to produce more platelets)

Aim to reduce risks of thrombosis
Aspirin
Keep platelets < 400 x 109/L (see treatment of ET)

Question 11

Symptoms of ET

Answer 11

o Incidental finding in half the patients
o Thrombosis (arterial or venous)  CVA, gangrene, TIA, DVT, PE
o Bleeding: mucous membrane and cutaneous
o Minor: headaches, dizziness, visual disturbances

Question 12

Diagnosis of ET

Answer 12

o Platelet count consistently above 600x109/L
o Megakaryocyte abnormalities and clustering
o No evidence of reactive thrombocytosis

o JAK2 V617F mutation [only present in 50% of ET patients so other criteria needed to diagnose]

Question 13

Treatment of ET

Answer 13

o	Aspirin (prevent thrombosis)
o	Anagrelide (specific inhibition of platelet formation; SEs = palpitation, flushing)
	WARNING: can accelerate myelofibrosis
o	Hydroxycarbamide (MAIN TREATMENT) = an antimetabolite  suppresses other cells as well

Question 14

Presentation of primary myelofibrosis

Answer 14

Presentations related to:
■ Cytopenias: anaemia or thrombocytopenia
■ Thrombocytosis
■ Splenomegaly: may be massive
■ Budd-Chiari syndrome
■ Hepatomegaly

Question 15

Haematoligical findings of PMF

Answer 15

Blood film:
• Leucoerythroblastic picture
• Tear drop poikilocytes
• Giant platelets
• Circulating megakaryocytes

Bone marrow:
• ‘Dry tap’

Question 16

Bad prognostic signs of PMF

Answer 16

Bad prognostic signs:
■ Severe anaemia <100g/L
■ Thrombocytopenia <100x109/l
■ Massive splenomegaly

■ Score 0 – median survival 15years
■ Score 4-6– median survival 1.3 years

Question 17

Primary Myelofibrosis treatment

Answer 17

Supportive: RBC and platelet transfusion often ineffective because of splenomegaly
■ Cytoreductive therapy: hydroxycarbamide (for thrombocytosis, may worsen anaemia)
■ Ruxolotinib: JAK2 inhibitor (high prognostic score cases)

Question 18

CML presentation

Answer 18

• Lethargy/ hypermetabolism/ thrombotic event : monocular blindness CVA, bruising bleeding
• Massive splenomegaly +/- hepatomegaly
• Hb and platelets well preserved or raised •Massive leucocytosis 50-200x109/L

Question 19

What is associated with CML

Answer 19

Philadephia chromosome- 9:22

BCR-ABL- expresses a fusion oncoprotein-constitutive tyrosine kinase activity. Drives myeloid proliferation

Question 20

Diagnosis of CML

Answer 20

• FBC and measure leucocyte count
• Cytogenetics and detection of Philadelphia chromosome
• RT-PCR of BCR-ABL fusion transcript which can be quantified by RQ-PCR to determine response to therapy

Question 21

Phases of CML

Answer 21

Chronic phase- Patients in the chronic phase typically have less than 10% blasts in their blood or bone marrow samples. These patients usually have fairly mild symptoms

Accelerated phase- The blood samples have 10-19% blasts
Basophils make up 20% or more of the blood

Blastic phase- >20%, spread to other tissues, with fever, WL, poor appetite

Question 22

Treatment of CML

Answer 22

Imatinib- Tyrosine kinase inhibitor

Question 23

If you see lymphadenopathy in a leukaemic picture- is it more likely myeloid or lymphoid

Answer 23

It is likely to be a LYMPHOID cause and not a MYELOID cause as the white cells circulate through lymph nodes and so will engorge them (myeloid cells will not circulate through these)