Haematology Myeloproliferative Disorders Flashcards Preview

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Flashcards in Haematology Myeloproliferative Disorders Deck (44):
1

Myeloproliferative disorders: Description

Clonal haematological disorders characterised by over-production of blood cells and a tendency to transformation to acute leukaemia.

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Myeloproliferative disorders: Epi

Generally diseases of middle or older age groups.
Incidence: 2 cases per 100,000

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Myeloproliferative disorders: Three related disorders with similar acquired genetic defects (e.g. Janus Kinase Jak-2 mutations)

1. Primary polycythaemia
2. Essential thrombocythaemia (increased platelets)
3. Idiopathic myelofibrosis

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Myeloproliferative disorders: Mixed myeloid progenitor

RBC/Platelets/ Neutophil/Monocyte/ Basophil/Eosinophil

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Myeloproliferative disorders: Similar disorders

Chronic myeloid leukaemia (CML)

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Myeloproliferative disorders: Essential thrombocythaemia

Increased platelet number

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Myeloproliferative disorders: Myelofibrosis

Affects stomal calsin BM – scarring and fibrosis in bone marrow

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Polycythaemia → Defined by

Defined by the packed cell volume (PCV): a raised PCV of >0.51 in males and >0.48 in females requires further investigation.

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Polycythaemia → Measure

The True red cell mass and the plasma volume can be measured.
Involves radionucelotide labelling of red cells and albumen, respectively (less common).

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Polycythaemia → The absolute measurements allows

“True” polycythaemia to be distinguished from an “apparent” polycythaemia (decreased plasma volume).

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Polycythaemia → Symptos and Signs of Primary Polycythaemia

Hyperviscosity:
Hypervolaemia:
Hypermetabolism:

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Hyperviscosity:

Haemostasis (thrombosis – stroke, transient ischaemic attacks, digital ischaemia), haemorrhage, headache

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Hypervolaemia:

Plethora, hypertension and splenomegaly

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Hypermetabolism:

Pruritis, weight loss, sweats, gout

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Polycythaemia → Packed cell volume >0.51 (males)
>0.48 (females) with a raised red cell mass (absolute) definition

Primary polycythaemia
Secondary polycythaemia

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Polycythaemia →Packed cell volume >0.51 (males)
>0.48 (females) Normal red cell mass diagnosis

Apparent polycythaemia

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Polycythaemia → True polycythaemia

Raised RBC
Plasma volume slightly reduced but overall volume higher

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Polycythaemia → Apparent polycythaemia

Overall blood volume is less. Red cell mass normal (Can occur burns, alcohol, smoking)

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Differential diagnosis of a true polycythaemia

Primary Polycythaemia
Secondary Polycythaemia

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Secondary Polycythaemia

Drive from EPO due to a stimulus.
• Hypoxaemia e.g. chronic lung disease, cyanotic congenital heart disease, sleep apnoea.
• Renal disease e.g. hypernephroma, polycystic kidney disease (cysts causes pressure on cells leading to increased EPO)
• Miscellaneous e.g. hepatomas, cerebellar haemangioma, massive fibroids, high oxygen affinity haemoglobins.

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Symptoms and Signs of Primary Polycythaemia

• Facial plethora
• Headache
• Mental clouding
• Pruritis
• Hypertension
• Splenomegaly
• Gout
• Occlusive vascular lesions e.g. stroke, transient ischaemic attacks, digital ischemia
• Bleeding
• Hyper viscosity

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Polycythaemia Specialist Investigations

1. Serum Erythropoietin → Low in primary polycythaemia
2. Jak 2 mutation
3. Bone marrow examination
4. Abdominnal ultrasound to assess spleen size

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Jak 2 mutation

Specific V617F mutation in Jak 2 signal transduction protein linked to erythropoietin receptor. This “activating” mutation promotes proliferation of stem cells.
Identified in 90% of patients with polycythaemia vera and 50% of patients with essential thrombocythaemia and myelofibrosis (30-50%) – permanently switched on – increased RBC.

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V617F

Found on cell surface involved in transfer of EPO binding signal to the cell

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Bone marrow examination for

Erythroid hyperplasia
Fibrosis (low levels)

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Treatment

1. Repeated venesections to maintain a PCV of <0.45 (aiming for (slightly lower than normal)
2. Hydroxyurea if there is also thrombocytosis (concern increase risk of leukaemia.
3. Low doe aspirin (if there are no bleeding manifestations) – prevent arterial clots (can’t tolerate other treatments)
4. Radioactive phosphorus

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Radioactive phosphorus

Single disease controls disorder for 12-18 months but associated with increased risk of leukaemia.
Reserved for elderly frail patients.

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Progression and Prognosis

Untreated patients: survival 18 months (clots and myelofibrosis and leukaemia)
Treated patents: survival 10-15 years
In the longer term, 20% of patients transforms to myelofibrosis and about 5% to acute leukaemia (need monitoring)

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Essential Thrombocythaemia: Definition

A myeloproliferative disorder characterised by the presence of a persistent thrombocytosis (platelet count >450 x 109/L) increased + 600

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Essential Thrombocythaemia: JAk2 mutation

Positive in 50% of cases: useful for diagnosis (not as useful as in polycythaemia)

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Essential Thrombocythaemia: Diagnosis

Otherwise, this is a diagnosis of exclusion and other reactive causes of a raised platelet count first need to be considered: e.g. infection, inflammation, malignancy and bleeding (reactive picture).

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Essential Thrombocythaemia: Presentation

• 25-50% of patients present with microvascular occlusive events (e.g. burning pain in extremities or digital ischaemia), major vascular occlusive events or haemorrhage (interference with clotting cascade).
• Erythromelalgia in essential – redness and burning the feet and hands
• Livedo reticularis in essential thrombocythaemia.

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Essential Thrombocythaemia: Blood film in thrombocythaemia

• Large Platelets (variation in size)
• Iron deficiency
• Hypochrominc RBCs – Iron deficiency
• CHECK THIS

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Essential Thrombocythaemia: Bone marrow morphology in essential thrombocytaemia

• Megakaryocytes and abnormal nucleation
• CHECK THIS

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Essential Thrombocythaemia: Treatment

1. Low dose aspirin (unless history of bleeding)
2. Hydroxyurea (carbomide(same thing))
3. Anagrelide (younger patients) – chemoagents
Transformatino to myelofibrosis or acute leukaemia may occur in a small minority of patients long term – Primary polycythaemia.

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Idiopathic Myelofibrosis: Main Clinical Features


• Bone marrow fibrosis (scar tissue leading to extramedullary)
• Extramedullary haemopoiesis (blood cell production in the liver and spleen)
• Splenomegaly – often massive
• Anaemia with leucoerythroblastic blood picture (precursors to RBC/WBC which you wouldn’t expect to see
• Weight loss, fatigue, bleeding

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Idiopathic Myelofibrosis: The Primary Malginant Process involves

Megakaryocytes: generate growth factors such as platelet-derived growth factor which stimulate fibroblast proliferation (stromal cell)

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Idiopathic Myelofibrosis:Fibroblast proliferation produce

Produce reticulin and scar bone marrow
1st – proliferation phase
2ndry – Splenomegaly and drop blood counts

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Idiopathic Myelofibrosis: X-ay changes

Myelosclerosis

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Idiopathic Myelofibrosis:Blood Picture

Leucoerythroblastic blood picture

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Idiopathic Myelofibrosis:Bone Marrow histology

Normally – fat cells and organised set of cells.
‘Starry night’
Stranding of cells into other areas – fat spaces

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Idiopathic Myelofibrosis: Determine severity of bone marrow histology

Fibrosis criteria to determine severity

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Idiopathic Myelofibrosis: Treatment

Blood Transfusions if symptomatic anaemia. Thrombocytopnaenia – symptomatic difficulty w/ splenomegaly therefore increased destruction and therefore not helpful.
Splenectomy to correct anaemia or treat painful enlargement of the spleen.

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Idiopathic Myelofibrosis:
Prognosis

2-4 years with death due to haemorrhage, infection or transformation to acute leukaemia → poor

Stem cell transplantation for younger patients (<65 years).
Jak 2 inhibitors for recently licensed: early trials show reduction in splenomegaly and constituitional symptoms and improved survival.

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