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Year 3: Haematology > Polcythaemia vera & Myelofibrosis > Flashcards

Polcythaemia vera & Myelofibrosis Flashcards

1
Q

Describe what is meant by a myeloproliferative disorder?

A

Myeloproliferative disorders involve the uncontrolled proliferation of a single type of stem cell

They are considered a form of cancer occurring in the bone marrow, although they tend to develop and progress slowly.

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2
Q

Myeloproliferative disorders that the potential to turn into which pathology? [1]

A

They have the potential to transform into acute myeloid leukaemia.

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3
Q

What are the three critical myeloproliferative disorders need to know? [3]

A
  • Primary myelofibrosis
  • Polycythaemia vera
  • Essential thrombocythaemia
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4
Q

Primary myelofibrosis; polycythaemia vera
and essential thrombocythaemia are all associated with mutations in which genes? [3]

A

JAK2
MPL
CALR

TOM TIP: The mutation to remember is JAK2. Treatment might involve JAK2 inhibitors, such as ruxolitinib

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5
Q

State the proliferating cell line in each of the following [3]

  • Primary myelofibrosis
  • Polycythaemia vera
  • Essential thrombocythaemia
A

Primary myelofibrosis:
- Haematopoietic stem cells

Polycythaemia vera:
- Erythroid cells

Essential thrombocythaemia:
- Megakaryocyte

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6
Q

State the blood finding result for each of the following

Primary myelofibrosis [3]
Polycythaemia vera [1]
Essential thrombocythaemia [1]

A

State the blood finding result for each of the following

Primary myelofibrosis:
- Low haemoglobin
- High or low white cell count
- High or low platelet count

Polycythaemia vera:
- High haemoglobin

Essential thrombocythaemia:
- High platelet count

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7
Q

Describe what is meant by myelofibrosis [1]

A

Myelofibrosis is where the proliferation of a single cell line leads to bone marrow fibrosis, where bone marrow is replaced by scar tissue.

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8
Q

What is myelofibrosis AKA? [1]

A

essential thrombocytopaenia

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9
Q

Describe the pathophysiology of myelofibrosis [4]

A

cytokines are released from the proliferating cells.: especially: fibroblast growth factor

FIbrosis decreases production of blood cells: ledas to low Hb; leukopaenia and thrombocytopaenia

When the bone marrow is replaced with scar tissue extramedullary haematopoiesis occurs

Production of blood cells in the liver and spleen causes hepatomegaly, splenomegaly, and portal hypertension. When it occurs around the spine, it can cause spinal cord compression.

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10
Q

Myelofibrosis usually occurs due to an initial mutation in which cell line? [1]

A

This is typically in the megakaryocyte cell line

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11
Q

Describe the initial presentation of myelofibrosis

A

20% asymptomatic

Hepatosplenomegaly

B symptoms: weight loss, fever and night sweats

Anaemia signs (conjunctival pallor etc)

Thrombembolic events

Portal hypertension (ascites, varices and abdominal pain)

Unexplained bleeding (due to low platelets)

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12
Q

[] is a complication of polycythaemia

A

Gout is a complication of polycythaemia

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13
Q

What peripheral blood film results would indicate myelofibrosis? [4]

A

pancytopenia and teardrop-shaped red cells
Anisocytosis
Blasts (immature red and white cells)

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14
Q

What investigational method is used to confirm a diagnosis of myelofibrosis? [1]

Testing for which genes can help diagnosis?

A

Bone marrow biopsy

Testing for the JAK2, MPL and CALR genes can help with diagnosis and management.

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15
Q

What would a biopsy show of a patient with myelofibrosis? [2]

A

Biopsy may demonstrate fibrosis and abnormal appearance of megakaryocytes

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16
Q

The cells in myelofibrosis are typically described in which way? [1]

A

dracocytes - tear drops

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17
Q

How would hepatic involement be suggested from investigations? [2]

A

PT and aPTT may be slightly prolonged

Raised alkaline phosphatase

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18
Q

What would an MRI scan of a patient with myelofibrosis show? [1]

A

MRI will show a decreased signal from the bone marrow as fat is replaced with fibrosis.

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19
Q

A formal diagnosis is based on the WHO criteria. This requires all three major criteria and one minor criterion.

What are these criteria?

A

Major criteria:
* Proliferation and atypia of megakaryocytes accompanied by fibrosis
* Not meeting WHO criteria for other myeloid neoplasms
* Presence of JAK2, CALR or MPL mutation or in the absence of these mutations, presence of another clonal marker or absence of reactive myelofibrosis

Minor criteria:
* Anemia not attributed to a comorbid condition
* Leukocytosis ≥11 x 109/L
* Palpable splenomegaly
* Raised LDH
* Leukoerythroblastosis

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20
Q

State 4 non-haematological causes of myelofibrosis [4]

A

Hyperparathyroidism
Systemic lupus erythematosus
Vitamin D deficiency
Systemic sclerosis

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21
Q
A
22
Q

What is the only curative option for myelofibrosis? [1]

A

Curative option:
* haematopoietic stem cell transplant.

23
Q

What are the symptomatic or palliative treatment options for myelofibrosis? [4]

A

Ruxolitinib:
- a JAK2 inhibitor
- effective regardless of JAK2 mutation status.

Hydroxyurea / (hydroxycarbamide)

interferon-alpha

24
Q

How can you treat the pain caused by extramedullary haematopoiesis? [1]

A

foci can be irradiated

25
Q

Which managment can be used to treat splenomegaly cause by myelofibrosis? [2]

A

Splenectomy or splenic irradiation

26
Q

Describe what is meant by polycythaemia vera (PV) [1]

A

A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets

27
Q

It is established that a mutation in [] is present in approximately 95% of patients with polycythaemia vera.

Describe the pathophysiology of PV [2]

A

established that a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera

The JAK2 gene encodes for a non-receptor tyrosine kinase involved in signal transduction pathways for various hematopoietic growth factors, including erythropoietin (EPO).

The JAK2 V617F mutation results in constitutive activation of the JAK-STAT signaling pathway, leading to increased proliferation and survival of hematopoietic progenitor cells, independent of EPO stimulation.

In addition to affecting erythropoiesis, the JAK2 V617F mutation also influences the proliferation of other myeloid progenitor cells. Consequently, patients with PV may present with increased white blood cell and platelet counts.

28
Q

What is the difference between primary and secondary polycythaemia? [2]

A

Primary polycythaemia:
- due to a mutation that results in an increase in the red cell mass.
- PV is the most common cause

Secondary polycythaemia:
- most commonly due to appropriate rises in EPO secondary to hypoxia: e.g. smoking; chronic lung disease; obesity and OSA
- also occurs due to EPO rising from: tumours; illicit EPO use; androgen use

29
Q

Which tumours typically cause a rise in EPO? [3]

A

Renal cell cancer
Wilms’ tumour
Adrenal tumours

30
Q

Describe the clinical features of polcythaemia vera

A
  • Ruddy complexion (red face)
  • Conjunctival plethora(the opposite of conjunctival pallor)
  • Haemorrhage
  • Splenomegaly
  • Hypertension
  • Pruritis after a hot bath
31
Q

Describe the investigations for PV? [4]

A

Full blood count/film:
- raised haematocrit
- raised neutrophils
- raised basophils
- raised platelets in half of patients

JAK2 mutation

Serum ferritin:
- low due to persistent production of RBC

Renal and liver function tests

32
Q

What diagnostic criteria needs to be met for a diagnosis of JAK2 positive PV? [2]

A

If JAK2 positive - need both of:

  • A1 High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)
  • A2 Mutation in JAK2
33
Q

If a patient is JAK2-negative, a diagnosis can occur due to meeting which criteria?

A

They have further guidance on the diagnosis of PV in the absence of a JAK2 mutation. This is very rare, far more complex and beyond the understanding typically required at an undergraduate level. For those interested see the full BSH guidelines for more detail.

34
Q

How do you manage PV? [5]

A

Venesection - first line treatment
- to keep the haemoglobin in the normal range

Aspirin 75mg daily
- to reduce the risk of thrombus formation

Chemotherapy
- (typically hydroxycarbamide: reduces the number of RBC

Phosphorus-32 therapy

35
Q

Cytoreductive therapy (Hydroxycarbamide / hydroxyurea) is considered in high-risk patients, defined by BSH as? [2]

A

Age ≥ 65 years and/or
Prior PV-associated arterial or venous thrombosis

36
Q

Cytoreductive therapy is considered in low risk patients who meet which criteria? [4]

A

Thrombocytosis (> 1500 × 109/l)
Progressive splenomegaly
Progressive leucocytosis (> 15 × 109/l)
Poor tolerance of venesection

37
Q

Patients suffering from PV have a high change of what complications?

A

Thrombotic events (DVT / PE) are a significant cause of morbidity and mortality

38
Q

5-15% patients go on to develop which two pathologies from PV? [2]

A

5-15% of patients progress to myelofibrosis
5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)

39
Q

PV typically presents at which age? [1]

A

PV can present at any age but most commonly presents in the 60’s and is very rare in childhood. It appears to be slightly more prevalent in men.

40
Q

When performing venesection, how much blood is typically removed from a patient? [1]

What is the target haemotocrit?

A

200-500ml at a time at intervals dependent on patient factors (e.g. size).

target of maintaining a haematocrit of < 0.45.

41
Q

A patient presents with unexplained splenomegaly, leukoerythroblastosis, and peripheral blood cytopenias. Which diagnostic test is most appropriate for confirming the diagnosis of myelofibrosis?
a) Bone marrow biopsy
b) Complete blood count (CBC)
c) Serum erythropoietin levels
d) JAK2 mutation testing

A

A patient presents with unexplained splenomegaly, leukoerythroblastosis, and peripheral blood cytopenias. Which diagnostic test is most appropriate for confirming the diagnosis of myelofibrosis?
a) Bone marrow biopsy
b) Complete blood count (CBC)
c) Serum erythropoietin levels
d) JAK2 mutation testing

42
Q

What constitutional symptoms are commonly associated with myelofibrosis?
a) Weight gain and fatigue
b) Night sweats and weight loss
c) Fever and headache
d) Hypertension and bradycardia

A

What constitutional symptoms are commonly associated with myelofibrosis?
a) Weight gain and fatigue
b) Night sweats and weight loss
c) Fever and headache
d) Hypertension and bradycardia

43
Q

When should cytoreductive therapy be initiated in myelofibrosis patients, according to NICE guidelines?
a) At the time of diagnosis
b) Only if the patient is symptomatic
c) After confirmation of JAK2 mutation
d) When platelet count exceeds 500 x 10^9/L

A

When should cytoreductive therapy be initiated in myelofibrosis patients, according to NICE guidelines?
a) At the time of diagnosis
b) Only if the patient is symptomatic
c) After confirmation of JAK2 mutation
d) When platelet count exceeds 500 x 10^9/L

44
Q

What is the recommended first-line therapy for myelofibrosis with intermediate-2 or high-risk disease, according to NICE guidelines?
a) Hydroxyurea
b) Ruxolitinib
c) Interferon-alpha
d) Allogeneic stem cell transplant

A

What is the recommended first-line therapy for myelofibrosis with intermediate-2 or high-risk disease, according to NICE guidelines?
a) Hydroxyurea
b) Ruxolitinib
c) Interferon-alpha
d) Allogeneic stem cell transplant

45
Q

For a patient with significant splenomegaly causing discomfort and early satiety, what is the first-line approach recommended by NICE?
a) Splenectomy
b) Radiation therapy
c) Ruxolitinib
d) Supportive care only

A

For a patient with significant splenomegaly causing discomfort and early satiety, what is the first-line approach recommended by NICE?
a) Splenectomy
b) Radiation therapy
c) Ruxolitinib
d) Supportive care only

46
Q

Which complication should be actively monitored in myelofibrosis patients receiving long-term hydroxyurea therapy?
a) Thrombocytosis
b) Pulmonary hypertension
c) Gastrointestinal bleeding
d) Secondary malignancies

A

Which complication should be actively monitored in myelofibrosis patients receiving long-term hydroxyurea therapy?
a) Thrombocytosis
b) Pulmonary hypertension
c) Gastrointestinal bleeding
d) Secondary malignancies

47
Q
A

Hydroxyurea

48
Q
A

Venesection

49
Q
A

polycythaemia secondary to erythropoietin secretion

50
Q
A

Budd-Chiari syndrome

51
Q
A

Mutation in JAK2

52
Q
A

Year 3: Haematology (23 decks)

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