3 - myeloproliferative disorders

Question 1

what is the meaning of word myeloproliferative?

Answer 1

myelo = bone marrow lineages (granulocytes, RBCs, platelets)

proliferative = rapid growth

Question 2

what are BCR-ABL1 negative myeloproliferative neoplasms?

Answer 2

1. primary myelofibrosis (proliferation of fibroblasts in bone marrow)
2. essential thrombocythaemia (overproduction platelets)
3. polycythaemia vera (overproduction RBCs)

Question 3

what are BCR-ABL1 positive myeloproliferative neoplasms?

Answer 3

chronic myeloid leukaemia (overproduction of granulocytes)

Question 4

when should you consider myeloproliferative neoplasms?

Answer 4

1. high granulocyte count
2. high RBC count
3. high platelet count
4. eosinophilia/basophilia
5. splenomegaly
6. thrombosis in unusual place

*particularly if no reactive explanation

Question 5

what are some clinical features relevant for all myeloproliferative disorders?

Answer 5

• can be asymptomatic
• increased cell turnover = fatigue, weight loss, gout, night sweats
• splenomegaly = abdo pain, left shoulder pain, early satiety
• marrow failure = pancytopenia
• thrombosis = claudication

Question 6

what is
a) polycythaemia vera?
b) secondary polycythaemia vera?
c) pseudopolycythaemia vera?

Answer 6

a) true overproduction of RBCs

b) increase in RBC but in response to chronic hypoxia, smoking or erythropoietin tumour

c) reduction in plasma volume so gives idea RBC high but actually RBC normal, plasma just low - caused by dehydration, diuretic, obesity (fat has liquid)

Question 7

what are clinical features of polycythaemia vera?

Answer 7

• ones from general (high cell turnover, splenomegaly, marrow failure, thrombosis)
• headache, fatigue (high blood viscosity)
• itch after exposed to water (aquagenic pruritus)

Question 8

what’s investigations done for polycythaemia vera?

Answer 8

• thorough history = to ensure no secondary or pseudo e.g. COPD, diuretic etc
• FBC/film
• JAK2 analysis = common mutation for PV

*investigations for secondary causes = drug, CXR, blood gases

Question 9

what is treatment of polycythaemia vera?

Answer 9

• venesect to haematocrit <0.45
• aspirin
• cytotoxic oral chemo = hydroxycarbamide
• interferon JAK inhibitor ruxolitinib

Question 10

what is essential thrombocythaemia?

Answer 10

= uncontrolled production of abnormal platelets (big bleeding risk since platelets not functioning well)

Question 11

what investigations done for essential thrombocythaemia?

Answer 11

• exclude other causes of thrombocytosis like blood loss, inflammation, malignancy, iron deficiency

CML can also present with high platelet so BCR-ABL1 to rule out

should do JAK2 again, can be in like 50%

bone marrow histology

Question 12

what is treatment of essential thrombocythaemia?

Answer 12

• aspirin
• hydroxycarbamide = controls proliferation

Question 13

what is myelofibrosis?

Answer 13

= healthy bone marrow is replaced by fibrosis, resulting in a lack of production of normal cells

Question 14

what can cause myelofibrosis?

Answer 14

• can be idiopathic
• can happen post polycythaemia or after essential thrombocythaemia

Question 15

what is buzzword that is seen on film for myelofibrosis?

Answer 15

leucoerythroblastic film

Question 16

what buzzword RBCs are seen in myelofibrosis?

Answer 16

teardrop RBCs

Question 17

what investigations done for myelofibrosis?

Answer 17

• blood film →teardrop RBCs & leucoerythroblastic
• dry aspirate
• fibrosis on trephine biopsy
• JAK2, CALR, MPL mutations

Question 18

what are causes of leucoerythroblastic?

Answer 18

1. reactive (sepsis)
2. marrow infiltration
3. myelofibrosis (important one)

Question 19

what is treatment of myelofibrosis?

Answer 19

• supportive care
• allogeneic stem cell transplant
• splenectomy
• JAK inhibitors →improve spleen size, survival

Question 20

what are symptoms of high cell turnover?

Answer 20

fatigue, weight loss, gout, night sweats