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Haematology > Myeloproliferative Disorders > Flashcards

Myeloproliferative Disorders Flashcards

1
Q

What does ‘myelo’ refer to?

A

Bone marrow lineage(s) – granulocytes, red cells and platelets

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2
Q

What does proliferative refer to?

A

Ability to grow or multiply by rapidly producing new tissue parts, cells, or offspring

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3
Q

What are myeloproliferative disorders?

A

Clonal haeomatopoietic stem cell disorders

i.e expansion of a single cell type

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4
Q

How are myeloproliferative disorders different from acute leukaemia?

A

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

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5
Q

In contrast with acute leukaemia, MATURATION of myeloproliferative disorders is _________

A

Preserved

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6
Q

In acute leukaemia, there is a block of __________

A

Maturation

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7
Q

What would histology of acute leukaemia look like?

A

Monoclonal - lots of primitive cells which look the same

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8
Q

What would histology of chronic myeloproliferative disorders be like?

A

Polyclonal - lots of different cell types

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9
Q

How can myeloproliferative disorders be broadly grouped?

A

As either BCR-ABL1 positive or BCR-ABL1 negative.

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10
Q

What MPD is BCR-ABL1 positive?

A

Chronic myeloid leukaemia

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11
Q

What does chronic myeloid leukaemia involve the overproduction of?

A

Granulocytes

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12
Q

What is the genetic aetiology of BCR-ABL1 conditions?

A

The philidelphia chromosome

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13
Q

What 3 MPD’s are BCR-ABL1 negative?

A
  1. Essential thrombocytopenia
  2. Polycythaemia ruba vera
  3. Idiopathic myelofibrosis
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14
Q

What is overproduced in essential thrombocytopenia?

A

Platelets

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15
Q

What is overproduced in polycythaemia ruba vera?

A

Red cells

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16
Q

** When should you suspect a MPD in someone? **

A 
High granulocyte count
\+/-
High platelet count
\+/- 
High red cell count
\+/-
Eosinophilia/basophilia
  • Splenomegaly
  • Thrombosis (in unusual places)

+

WITH NO EXPLANATION OF CAUSE

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17
Q

What should you always do if you get an unusual blood count?

A

Take another sample

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18
Q

What happens, pathologically, in chronic myeloid leukaemia?

A

Proliferation of myeloid cells.

  • Granulocytes and their precursors.
  • Other lineages (platelets).
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19
Q

In the past, what was the course of chronic myeloid leukaemia (CML) like?

A

Initial chronic phase with intact maturation for 3-5 years, followed by a ‘blast crisis’ reminiscent of acute leukaemia with maturation defect.
This was fatal without stem cell/bone marrow transplantation in the chronic phase.

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20
Q

What are the 3 phases of CML?

A
  • Chronic phase.
  • Accelerated phase.
  • Blast crisis - loss of maturation
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21
Q

Describe the chronic phase.

A

Excess of mature neutrophils, with some visible precursors

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22
Q

Describe the accelerated phase.

A

Proportion of mature cells in the body is dropping relative to the amount of primitive cells

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23
Q

Describe the blast crisis.

A

Monomorphic, primitive cells

i.e loss of maturation

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24
Q

Outline the clinical features of CML.

A
  • Asymptomatic.
  • Splenomegaly – early satiety, palpable spleen.
  • Hypermetabolic symptoms.
  • Gout (due to high cell turnover)
  • Problems related to hyperleukocytosis (sludging of blood in small vessels)
  • Priapism (prolonged erection).
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25
Q

How can splenomegaly often present?

A

Palpable spleen OR early satiety - feeling full quicker because the large spleen is pressing on the stomach

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26
Q

What are the lab features in CML?

A

Blood count changes:

  • Normal/decreased Hb.
  • Neucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia.
  • Thrombocytosis
  • Bone marrow changes

Basically - increased WBC, increased platelets, normal or low Hb

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27
Q

What high cell count is particularly indicative of CML?

A

Basophilia - not many conditions cause this

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28
Q

The higher the white count, the more likely you are to have microvascular complications.

A

T

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29
Q

** What is the genetic hallmark of CML? **

A

The Philadelphia chromosome – translocation between chromosomes 9 and 22; ABL and BCR genes fuse together

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30
Q

What does the philidelphia chromosome result in?

A

A new (chimaeric) gene: BCR-ABL1

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31
Q

What is the gene product of BCR-ABL 1?

A

A tyrosine kinase

32
Q

What does the tyrosine kinase, as a result on BCR-ABL 1 do?

A

Abnormal phosphorylation (signalling), leading to the haematological changes seen in CML.

33
Q

What can thus be used as treatment for CML?

A

Tyrosine kinase inhibitors e.g. Imatinib

34
Q

What are the main BCR-ABL 1 negative conditions?

A
  1. Polycythaemia rubra vera (PRV).
  2. Essential thrombocythaemia (ET).
  3. Idiopathic myelofibrosis (IMF).
  4. Others.
35
Q

What features are common to all MPD’s?

A
  • Can be asymptomatic.

* Increased cellular turnover.

36
Q

Clinically, what does an increased cel turnover (seen in MPD’s) result in?

A

Gout, fatigue, weight loss, sweats.

37
Q

What are the symptoms of splenomegaly?

A
  • LUQ pain

* Early satiety

38
Q

Why does marrow failure occur in MPD’s?

A

Due to fibrosis or leukaemic transformation

39
Q

Why do people with MPD’s get thrombosis in random places?

A

Due to sludging of blood in smaller vessels

40
Q

What kind of thrombosis can people with MPD’s get?

A

Arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia

41
Q

How can PRV be identified?

A

A high haemoglobin/haematocrit, accompanied by erythrocytosis BUT can have excessive production of other lineages.

42
Q

What is erythrocytosis?

A

A true increase in red cell mass

43
Q

What must you always distinguish PRV from?

A

SECONDARY POLYCYTHAEMIA

44
Q

What can secondary polycythaemia cause?

A

Chronic hypoxia, smoking, erythropoietin-secreting tumour etc.

45
Q

What can pseudopolycythaemia cause?

A

Dehydration, diuretic therapy, obesity.

46
Q

What does pseudopolycythaemia occur due to?

A

A reduction in plasma volume, resulting in an apparent increase in red cells

47
Q

Some of the clinical features of PRV are similar to CML

A

T

48
Q

** What are the specific signs and symptoms related to PRV? **

A

Headache, fatigue (REMEMBER BLOOD VISCOSITY IS RAISED, NOT PLASMA VISCOSITY).

Itch – aquagenic pruritis (itch on exposure to warm water).

49
Q

If someone says they are itchy when they go in the shower, what should you think?

A

PRV

50
Q

What causes secondary polycythaemia?

A

Chronic hypoxia

Basically in someone with lung disease, sleep apnoea or who smokes, they will become chronically hypoxic over time and they will have reduced oxygen carrying capacity of the blood

To try and compensate for this, the body overproduced Hb (polycythaemai) in an attempt to raise oxygen carrying capacity of the blood

51
Q

What should be done in history and exam of someone with suspected PRV?

A
  • History - rule out secondary polycythaemia
  • Exam - look for splenomegaly
  • FBC and film - do this to make sure it wasn’t just a false result
  • RULE OUT SECONDARY - CXR, O2 sats
52
Q

What mutation is seen in PRV?

A

Jak2

53
Q

What is JAK2?

A

A kinase

54
Q

What % of patients with PRV will have the JAK2 mutation?

A

95%.

55
Q

What does the JAK2 mutation result in?

A
  • Loss of auto-inhibition, and activation of erythropoiesis in the absence of ligand.
  • Mutational analysis forms part of initial screening and has replaced a number of other tests in routine practice.
56
Q

How is PRV treated?

A
  • Venesect to haematocrit <0.45 as main risk is having thrombotic events.
  • Aspirin.
  • Cytotoxic oral chemotherapy e.g. hydroxycarbamide.
57
Q

What is essential thrombocythaemia?

A

Uncontrolled production of ABNORMAL platelets

58
Q

What does the abnormal platelets in ET lead to?

A
  • Thrombosis

* Bleeding - at high levels due to a vWF factor problem

59
Q

How do we know that ET is a MPD and not just a reactive problem?

A

Although there are way too many platelets, in ET the platelets are abnormally large too

60
Q

What are the main clinical features of ET?

A
  • Vaso-occlusive complications.
  • Bleeding – unpredictable risk, especially at surgery
  • Purpura
  • Weakness
  • Fatigue
  • SOB on exertion
  • Early satiety
61
Q

Outline how the diagnosis of ET can be confirmed?

A
  1. Raised platelets.
  2. Exclude reactive thrombocytosis (IMPORTANT!!!) - blood loss, inflammation, malignancy
  3. Exclude CML - this can present more with a thrombocytosis in initial stage.
  4. Genetics.
  • JAK2 mutations in 50%.
  • CALR (calreticulin) in those without mutant JAK2.
  • MPL mutation.
  1. Characteristic bone marrow appearances.
    * Too many megakaryocytes, forming clusters in the bone marrow.
62
Q

How is ET treated?

A
  1. Aspirin

2. Chemo drugs e.g hydroxycarbamide

63
Q

What is myelofibrosis?

A

Bone marrow disorder that disrupts your body’s normal production of blood cells

The result is extensive scarring in your bone marrow, leading to severe anemia, weakness, fatigue and often an enlarged spleen

It is a MPD !!!

64
Q

What can myelofibrosis arise due to?

A
  • IDIOPATHIC (or agnogenic myeloid metaplasia) cause.

* Post-polycythaemia (raised Hb) or essential thrombocytopenia.

65
Q

What is seen in peripheral blood of someone with idiopathic myelofibrosis?

A

Teardrop shaped RBC’s

66
Q

What is the blood film appearance of idiopathic myelofibrosis?

A

Leukoerythroblastic

67
Q

What is idiopathic myelofibrosis?

A

BONE MARROW FIBROSIS !!!!

68
Q

What does the bone marrow fibrosis in idiopathic myelofibrosis result in?

A

Extramedullary hematopoiesis in the liver and spleen (cause of massive splenomegaly)

69
Q

Outline the clinical features of MF.

A
  1. Marrow failure: anaemia, bleeding. infection
  2. Splenomegaly: LUQ pain, portal hypertension
  3. Hypercatabolism.
70
Q

How is a diagnosis of MF made?

A
  • Typical blood film - teardrop shaped RBC’s and leucoerythroblastic
  • Dry aspirate - get a dry tap because scarring in the bone marrow prevents us from getting any cells out.
  • Fibrosis on trephine biopsy.
  • Mutational analysis.
71
Q

What mutations are found in some MF?

A

JAK2 or CALR

72
Q

What is a leucoerythroblastic film?

A

The presence of erythroblasts (nucleated RBC) and myelocytes (neutrophil precursors) in the blood

  • Erythroblasts + Myelocytes (neutrophils precursor)
73
Q

** What are the 3 causes of a leucoerythroblastic film? **

A
  1. Reactive – sepsis.
  2. Marrow infiltration.
  3. Myelofibrosis.
74
Q

How is MF treated?

A
  1. Supportive care – blood transfusions, platelets, antibiotics.
  2. Allogenic stem cell transplantation in a select few.
  3. Splenectomy – BUT CONTROVERSIAL.
  4. JAK2 inhibitors (improve spleen size, QoL, ? survival).
75
Q

List causes of raised granulocytes.

A
  • Infection e.g. pyogenic bacteria causing neutrophilia.

* Physiological e.g. post-surgery, steroids.

76
Q

List causes of raised platelets.

A
  • Infection.
  • Iron deficiency.
  • Malignancy.
  • Blood loss.
77
Q

List causes of raised red cells.

A
  • Dehydration (diuretics) – pseudopolycythaemia.

Haematology (26 decks)

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