Chronic myeloproliferative disorders

Question 1

What is a myeloproliferative disorder?

Answer 1

Multiplication of cells of bone marrow lineage

Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells

Maturation of cells relatively preserved

Question 2

Sub types of myeloproliferative disorders?

Answer 2

BCR-ABL1 negative

BCR-ABL1 positive

Question 3

BCR-ABL1 negative?

Answer 3

Idiopathic myelofibrosis
Essential thrombocythaemia
Polycythaemia rubra vera

Question 4

BCR-ABL1 positive?

Answer 4

Chronic myeloid leukaemia

Question 5

When to consider MPD?

Answer 5

High granulocytes
High RBC
High PTs
Eosino/basophilia
Splenomegaly
Thrombois in an unusual place

Question 6

What is chronic myeloid leukaemia?

Answer 6

Uncontrolled proliferation of myeloid cells eg granulocytes + precursors and platelets

Fatal without stem cell/bone marrow transplantation in chronic phase

Question 7

Features of CML?

Answer 7

Assymptomatic
Splenomegaly
Hypermetabolic syndrome
Gout
Misc

Question 8

Lab changes in CML?

Answer 8

Normal/decreased Hb
Leucocytosis
Neutrophilia
Eosinophilia
Basophilia
Thrombocytosis

Question 9

Genetics of CML?

Answer 9

Philadelphia chromosome resulting in BCR-ABL1 gene

Tyrosine kinase which cause abnormal phosphorylation leading to haem changes

Responds to tyrosine kinase inhibitors eg imatinib

Question 10

Features common to MPD?

Answer 10

Asymptomatic
Increased cell turnover (gout, fatigue, wt loss, sweats)
Symptoms os splenomegaly
Marrow failure
Thrombosis

Question 11

What is polycythaemia rubra vera?

Answer 11

High haemoglobin/haematocrit accompanied by erythrocytosis

Question 12

Secondary polycythaemia causes?

Answer 12

Chronic hypoxia
Smoking
Epo tumour

Question 13

Pseudopolycythaemia?

Answer 13

Dehydration, diuretic therapy, obesity

Question 14

PRV features?

Answer 14

Common to MPD
Headache
Fatigue (as blood viscosity raised)
Itch (aquagenic pruritus)

Question 15

Ix of PRV?

Answer 15

History
Examination
FBC, film
JAK 2 Mutation (95%)

Question 16

Results of JAK 2 mutation>

Answer 16

Mutation results in loss of auto-inhibition

Activation of erythropoiesis in absence of ligand

Question 17

PRV treatment?

Answer 17

Venesect to haematocrit<0.45

Aspirin

Oral chemo eg hydroxycarbamide

Question 18

What is essential thrombocytosis?

Answer 18

Uncontrolled production of abnormal platelets

Causes thrombosis
At high levels can cause bleeding due to acquired von Willebrand disease

Question 19

Features of ET?

Answer 19

Common to MPD (Particularly) vasoocclusive)

Bleeding

Question 20

ET diagnosis?

Answer 20

Exclude reactive thrombocytosis immediately (blood loss, inflammation, malignancy, iron deficiency)

Exclude CML

Jak2 in 50%
CALR in those without mutant JAK2

Bone marrow

Question 21

ET treatment?

Answer 21

Anti platelets

Cytoreductive eg hydroxycarbamide, anagrelide, interferon alpha

Question 22

Features of Idiopathic myelofibrosis?

Answer 22

Marrow failure
Bone marrow fibrosis
Extramedullary haematopoiesis
Leukoerythroblastic film appearances
Teardrop shaped RBC in peripheral blood

Splenomeg
Hypercatabolism

Question 23

Treatment of MF?

Answer 23

Supportive(Transfuse, pts, abx)
Allogenic stem cell transplant
Splenectomy (although controversial)