Myeloproliferative Disorders

Question 1

What causes myeloproliferative disorders?

Answer 1

Clonal proliferation of haematopoietic myeloid stem cells in the bone marrow

Question 2

What are the myeloproliferative disorders?

Answer 2

RBC - polycythaemia vera
WBC - Chronic Myeloid Leukaemia
Platelets - Essential thrombocythaemia
Fibroblasts - Myelofibrosis

Question 3

What is relative polycythaemia?

Answer 3

Reduced plasma volume
Normal RBC mass

Due to dehydration, associated with obesity, HTN, high alcohol

Question 4

What is absolute polycythaemia?

Answer 4

Increased RBC mass

Primary - polycythaemia vera
Secondary - hypoxia (e.g. high altitudes, chronic lung disease, cyanotic congenital heart disease, heavy smoking)
Increased erythropoietic secretion (RCC, hepatocellualr carcinoma)

Question 5

What is polycythaemia vera? Cause?

Answer 5

Malignant proliferation of a clone derived from one pluripotent stem cell

JAK2 mutation
Erythroid progenitor offspring are unusual in not needing erythropoietin to avoid apoptosis

Excessproliferation of RBCs, WBCs and platelets leading to hyperviscosity and thrombosis

Question 6

How does polycythaemia vera present? Classic symptoms?

Answer 6

Asymptomatic
Detected on FBC
OR

Vague symptoms due to hyper-viscosity:
Headache, dizziness, tinnitus, visual disturbance

Itching after hot bath
Erythromelalgia (burning sensation in fingers and toes)

Question 7

What are signs of polycythaemia vera??

Answer 7

Facial plethora
Splenomegaly
Gout due to increased urate from RBC turnover
Arterial or venous thrombosis

Question 8

Ix in polycythaemia vera?

Answer 8

FBC:
Raised red cell count
Raised Hb
Raised Haematocrit
Raised PCV
Raised WBC
Raised platelets

Raised B12

Bone marrow aspirate and trephine
Hypercellularity
Erythroid hyperplasia

Cytogeneitcs as required to differentiate from CML (philadelphia chromosome)

Reduced serum erythropoietin

Raised red cell mass on radioactive chromium labelled RBC studies and splenomegaly with normal pO2 is diagnostic

Question 9

Mx for polycythaemia vera?

Answer 9

Keep HCT < 0.45 to reduce thrombosis risk

Venesection in low risk young patients

If high risk (>60, previous thrombosis) use hydroxycarbamide

Alpha-interferon in women of child bearing age

Aspirin 75mg

Question 10

Complications of polycythaemia vera?

Answer 10

Thrombosis
Haemorrhage (defective platelets)
Transition to myelofibrosis

Question 11

What is essential thrombocytopenia? Presentation? Mx?

Answer 11

Clonal proliferation of megakaryocytes leading to raised platelets >1000
With abnormal function causing bleeding or arterial and venous thrombosis

Microvascular occlusion - headache, chest pain, light headedness, erythromelalgia (burning in fingers and toes)

Mx:
Aspirin 75mg
Hydroxycarbamide

Question 12

What is myelofibrosis? Presentation?

Answer 12

Hyperplasia of megakaryocytes which produce platelet derived growth factor leading to intense marrow fibrosis and haematopoiesis in spleen and liver

Massive hepatosplenomegaly

B symptoms
Abdominal discomfort due to splenomegaly
Bone marrow failure: Anaemia, infection, bleeding

Question 13

What is seen on film in myelofibrosis?

Diagnosis?

Answer 13

Leukoerythrobvlastic cells - nucleated red cells)
Tear drop RBCs

Bone marrow trephine for diagnosis

Question 14

What is Mx in myelofibrosis?

Answer 14

Marrow support

Allogenic stem cell transplant in young