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Gwen - Haematology > Myeloproliferative syndromes > Flashcards

Myeloproliferative syndromes Flashcards

1
Q

What are myeloproliferative disorders?

A

Myeloproliferative disorders most often represent a neoplastic proliferation of a marrow myeloid progenitor cell with differentiation to the mature form(s) (in contrast to the acute myeloid leukaemias, where maturation is very limited).

The normal control mechanisms governing the cell line(s) involved are no longer active, allowing accumulation of erythrocytes, platelets or leucocytes. Proliferation of mega- karyocytes produces growth factors causing a secondary overgrowth of fibroblasts (myelofibrosis).

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2
Q

Point mutations in which cell signalling gene have been implicated in myeloproliferative disorders?

A

JAK2 kinase

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3
Q

How do myeloproliferative disorders tend to present?

A

As a macrocytic anaemia and pancytopenia

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4
Q

General management of myeloproliferative disorders

A

Supprotive multiple transfusions of red cells or platelets as needed, or stem cell transplantation fo the few young patients.

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5
Q

What are the main myeloproliferative disorders?

A
  • Polycythaemia Rubra Vera
  • Essential Thrombocythaemia
  • Myelofibrosis
  • CML
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6
Q

What is the main cell type proliferating in polycythaemia rubra vera?

A

RBCs

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7
Q

What is the main cell type that is proliferating in essential thrombocythaemia?

A

Platelets

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8
Q

What is the main cell type that is proliferating in myelofirbosis?

A

Fibroblasts

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9
Q

What is the main cell type with is proliferating in CML

A

White blood cells

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10
Q

What is polycythaemia rubra vera (PV)?

A

PV is a clonal stem cell disorder in which there is an alteration in the pluripotent progenitor cell leading to excessive proliferation of erythroid, myeloid and megakaryocytic progenitor cells. This usually corresponds with an increase in haemoglobin concentration and haematocrit.

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11
Q

Whats the difference beteen apprant erythrocytosis and true polycythaemia?

A

Apparant erythrocytosis - too little plasma (eg dehydration, excessive alcohol, diuretic therapy)

True polycythaemia - too many red cells.

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12
Q

What are secondary causes of polycythaemia?

A
  • Hypoxia
  • Increased EPO secretion
  • (Hypovolemia - apparent erythrocytosis - too little plasma)
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13
Q

What are causes of hypoxia that cause secondary polycythaemia?

A
  • Hypoxia
    • High altitudes
    • Chornic lung disease
    • Cyanotic congenital heart disease
    • Sleep apnoea
    • Morbid obesity
    • Heavy smoking
  • Increased EPO
    • ​EPO secreting tumour
    • Renal - hydronephrosis, polycystic kidneys, renal cell carcinoma
    • Liver - polycystic liver diease, hepatocellular carcinoma
    • Endocrine - cushings, parathyroid carcinoma, adenoma
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14
Q

What are causes of increased EPO secretion that cause secondary polycythaemia?

A
  • Renal cell carcinoma, Wilm’s tumour
  • Hepatocellular carcinoma
  • Adrenal tumours
  • Cerebellar haemangioblastoma
  • Massive uterine Leiomyoma
  • Overadministration of EPO
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15
Q

Is there any risk of progression in secondary polycythaemia?

A

Nope - not to myelofibrosis nor AML.

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16
Q

What is relative polycythaemia?

A

Where the red cell volume is normal but there is a decrease in the plasma volume

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17
Q

What are causes of relative polycythaemia?

A
  • Dehydration
  • Burns
  • Stress
  • Spurious polycythaemia
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18
Q

What is the definition of polycythaemia?

A

Defined as an increase in haemoglobin, PCV and red cell count

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19
Q

What is the most accurate measure of polycythaemia?

A

Packed cell volume

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20
Q

What percentage of those with polycythaemia rubra vera have acquired mutations in JAK2 kinase gene?

A

95%

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21
Q

What is JAK2?

A

Cytoplasmic tyrosine kinase that transduces signals, especially those triggered by haematopoietic growth factors such as erythropoietin, in normal and neoplastic cells.

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22
Q

What symptoms might someone experience with polycythaemia rubra vera?

A

May be asymptomatic, or:

  • Headaches
  • Dizziness
  • Tinnitus
  • Visual disturbance
  • Itch after hot bath
  • Erythromelalgia
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23
Q

What are signs of polycythaemia rubra vera?

A
  • Plethora
  • Splenomegaly
  • Gout
  • Venous or Arterial Thrombotic signs - PE, Cardiac, DVT
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24
Q

Why do individuals with polycythaemia rubra vera get headaches?

A

Hyperviscosity

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25
Q

Why do individuals with polycythaemia rubra vera get plethora?

A

An excess of blood in a body part, usually used to describe a red, florid complexion

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26
Q

What are common causes of plethora?

A
  • Chronic alcoholism
  • Cushing’s disease
  • Parenchymal lung disease
  • Menopause
  • Hyperthyroidism
  • Mitral stenosis
  • Polycythaemia
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27
Q

How would you investigate someone for potential polycythaemia rubra vera?

A
  • Consider blood gas/SpO2?
  • Bloods - FBC, U+E’s, PCV, urate, alk phosphatase, B12, EPO levels
  • Bone marrow biopsy
  • Cytogenetics
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28
Q

What might you find when investigating FBC in someone with Polycythaemia rubra vera?

A
  • Increased RBC
  • Increased Hb
  • Increased Hct
  • Possibly increased WCC and platelets

Decreased MCV

Decreased ferritin

29
Q

Why would you perform U+E’s in someone with polycythaemia?

A

See if kidney’s are working properly (secondary causes) and to see if they are dehydrated (relative causes)

30
Q

What might you see on investigation of B12 levels in someone with polycythaemia rubra vera?

A

Increased B12

31
Q

What might you see when investigating EPO levels in someone with polycythaemia rubra vera?

A

Decreased levels - suppressed by feedback from increased RBC levels

32
Q

Why is it important to perform EPO testing in the context of polycythaemia?

A

To see if the polycythaemia is primary or secondary

33
Q

What might you see on bone marrow biopsy in someone with polycythaemia rubra vera?

A

Hypercellularity with erythroid hypercellularity

34
Q

What might you find on cytogenetic analysis in someone with polycythaemai rubra vera?

A

JAK2 V617F mutation

35
Q

What are the major criteria for the diagnosis of polycythaemia rubra vera?

A
  • Haemoglobin
    • >185 g/L in men
    • >165 g/L in women
    • Other evidence of increased red cell volume
  • Presence of JAK2 tyrosine kinase V617F or other functionally similar mutation
36
Q

What are the minor criteria for the diagnosis of polycythaemia rubra vera?

A
  • Bone marrow biopsy - hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic and megakaryocytic proliferation
  • Serum erythropoietin level below the reference range for normal
  • Endogenous erythroid colony (EEC) formation in vitroa
37
Q

Why might you consider blood gas/SpO2 in someone with polycythaemia?

A

To see if hypoxia is driving the polycythaemia

38
Q

How would you manage polycythaemia rubra vera?

A
  • Venesection - in an attempt to reduce cell volume
  • Hydroxycarbamide
  • Low dose aspirin - 25 mg
39
Q

What volume is normally removed in venesection?

A

400-500 mL

40
Q

What Hct are you aiming for in treatment of polycythaemia rubra vera?

A

<0.45

41
Q

What percentage of those with polycythaemia rubra vera develop into AML?

A

5%

42
Q

What percentage of those with polycythaemia rubra vera develop into myelofibrosis?

A

30%

43
Q

What are the main complications of polycythaemia rubra vera?

A

Thrombosis and haemorrhage

44
Q

What should you never give to someone with polycythaemia rubra vera?

A

Iron supplementation - fuels the uncontrolled erythropoeisis

45
Q

Why are some with polycythaemia rubra vera iron deficient?

A

Use up iron stores for overproducing red cells

46
Q

What is essential thrombocythaemia?

A

Essential thrombocythaemia (ET) is a myeloproliferative disorder closely related to PV. Patients have normal Hb levels and WBC but elevated platelet counts. At diagnosis the platelet count will usually be >600 × 109/L, and may be as high as 2000 × 109/L or rarely even higher.

47
Q

How does essential thrombocythaemia present?

A
  • Microvascular occlusion
    • Headaches
    • Atypical chest pain
    • Light headedness
    • Erythromelalgia
  • Thrombotic events - due to high platelet levels
  • Bleeding events - due to platelet dyfunction at high levels
  • Mild Splenomegaly
48
Q

What is important to do when investigating essential thrombocythaemia?

A

Exclude other causes of thrombocytosis

49
Q

What investigations would you do if you suspected essential thrombocythaemia?

A
  • Bloods - FBC
  • Cytogenetics? - JAK2
50
Q

How would you manage someone with essential thrombocythaemia?

A
  • Low-dose aspirin - 75mg
  • Hydroxycarbamide
51
Q

Why would you use hydroxycarbamide in polycythaemia rubra vera?

A

Advanced disease - suppress erythropoiesis

52
Q

What can essential thrombycythaemia transform into?

A
  • Polycythaemia rubra vera
  • Myelofibrosis
  • Acute myeloid leukamia
53
Q

At what platelet level is pradoxical haemorrhage likely to occur in essential thrombocytaemia?

A

> 1000x109 g/L

54
Q

What is myelofibrosis?

A

Also known as myelosclerosis, myelofibrosis (MF) is characterised by the predominant features of gross marrow fibrosis with massive extramedullary haemopoiesis in liver and spleen. The fibrosis is reactive (a polyclonal proliferation of fibroblasts is present).

Factors released from pathological megakaryocytes which proliferate in the bone marrow are thought to be the stimulus to the fibroblastic response. It is a chronic disorder of late middle age and beyond.

55
Q

What stimulates fibroblasts to cause fibrosis in myelofirbrosis?

A

PDGF and TGFβ are released by megakaryocytes

56
Q

What are symptoms of myelofibrosis?

A

Presents insidiously

  • Lethargy
  • Weakness
  • Weight loss
  • ‘fullness’ in the upper abdomen - due to splenomegaly.
  • Severe pain on respiration - may indicate perisplenitis secondary to splenic infarction
  • Bone pain
  • Gout
57
Q

What are signs of myelofibrosis?

A
  • Anaemia
  • Fever
  • Massive splenomegaly
  • Bruising
  • Bleeding
58
Q

Why does bleeding occur in myelofibrosis?

A

Due to thrombocytopenia or abnormal platelet function

59
Q

What can cause splenic pain in myelofibrosis?

A

Perisplenitis secondary to splenic infarction

60
Q

What investigation would you perform if you suspected myelofibrosis?

A
  • Bloods - FBC, Clotting screen
  • Blood film
  • Bone marrow aspiration
  • Cytogenetics
61
Q

What might you see on investigation of FBC in someone with myelofibrosis?

A
  • WBC count may be over 100 × 10<span>9</span>/L
    • Differential may be very similar to that seen in CML
    • Leucopenia may develop late on
  • Increased platelet - later stages may be low
62
Q

What might you see on investigaiton of bone marrow aspirate in someone with myelofibrosis?

A

Often unsuccessful - gives a clue to the presence of the condition

Bone marrow trephine

  • Markedly increased fibrosis
  • Increased megakaryocytes
63
Q

What is a bone marrow trephine?

A

Bone marrow biopsy

64
Q

What might you find on investigation of blood film in myelofibrosis?

A
  • Leucoerythroblastic cells - nucleated RBCs
  • Poikilcytosis - peardrop RBCs
65
Q

How would you manage someone with myelofibrosis?

A

General supportive measures

  • Blood transfusion
  • Folic acid
  • Analgesics
  • Allopurinol

Surgery

  • Splenectomy

Allogeneic stem cell transplantation

66
Q

Why might you perform a splenectomy in someone with myelofibrosis?

A
  • If the spleen is very large and painful
  • Transfusion requirements are high
  • May relieve severe thrombocytopenia
67
Q

What is the prognosis for someone with myelofibrosis?

A

4-5 years median survival

68
Q

What proportion of those who die from myelofibrosis die due to transformation to acute myelooid leukaemia?

A

20-30%

69
Q

What are the main causes of death in myelofibrosis?

A
  • Cardiovascular disease
  • Infection
  • GI bleeding

Gwen - Haematology (33 decks)

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