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Year 3 Clinical > Myeloproliferative Disorders (MPD) > Flashcards

Myeloproliferative Disorders (MPD) Flashcards

1
Q

Define myeloproliferative?

A

Proliferation down the myeloid bone marrow lineage, i.e: granulocytes, red cells and platelets

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2
Q

What are MPDs?

A

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

NOTE - in contrast to acute leukaemia, maturation is relatively preserved

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3
Q

Compare microscopy of normal bone marrow, acute leukaemia and MPD?

A

Normal - mixture of mature and immature cells, with some marrow spaces

Acute leukaemia - monomorphic, hypercellular appearance, with many of the same type of cell (monoclonal); there are many immature cells (blasts)

MPD - many mature myeloid cells are present (hypercellular)

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4
Q

Major classification system of MPDs?

A

BCR-ABL1 -ve

OR

BCR-ABL1 +ve

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5
Q

Types of BCR-ABL1 -ve sub-types of myeloproliferative disorders?

A

Idiopathic myelofibrosis

Polycythaemia Rubra Vera - over-production of rbcs

Essential thrombocytopaenia - over-production of platelets

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6
Q

Types of BCR-ABL1 +ve sub-types of myeloproliferative disorders?

A

Chronic Myeloid Leukaemia (CML) - over-production of granulocytes; characterised by the Philadelphia chromosome

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7
Q

Signs potentially indicating MPD?

A 
High Granulocyte count
\+/-
High Red cell count / haemoglobin
\+/-
High Platelet count
\+/-
Eosinophilia/basophilia (usually has a non-reactive cause)

Splenomegaly

Thrombosis in an unusual place

NOTE - without a reactive explanation

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8
Q

Which MPD usually causes splenomegaly?

A

Myelofibrosis

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9
Q

Areas in which thrombosis can occur with MPD?

A

Typical areas, e.g: DVT, MI

Atypical areas, e.g: portal vein thrombosis

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10
Q

What does CML involve?

A

Proliferation of myeloid cells, mainly granulocytes and their precursors, although it also affects other lineages, like PLTs

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11
Q

Manifestation of CML historically?

A

Chronic phase, with intact maturation, for 3-5 years, followed by a ‘blast crisis’ (similar to acute leukaemia with a maturation defect)

It was fatal without a stem cell/bone marrow transplantation in the chronic phase

NOTE - the chronic phase had excess, mature neutrophils and their precursors; the blast crisis inv. over-production of primitive blood cells

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12
Q

Clinical features of CML?

A

Asymptomatic (often an incidental finding)

Splenomegaly

Hypermetabolic symptoms

Gout (due to high cell turnover)

Miscellaneous:
• Issues due to hyperleucocytosis
• Priapism, visual disturbances and other microvascular problems

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13
Q

Diagnosis of CML?

A

Blood count:
• Normal or reduced Hb
• Leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
• Thrombocytosis

Bone marrow

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14
Q

Features of MPD blood count compared to reactive changes?

A

BASOPHILIA AND EOSINOPHILIA are less common with reactive changes

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15
Q

What is the hallmark of CML?

A

Philadelphia chromosome (translocation from chromosome 22 to 9); this fuses 2 genes, BCR and ABL, forming a new chimeric gene

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16
Q

Gene product of the philadelphia chromosome in CML?

A

Tyrosine kinase, which causes abnormal phosphorylation (signalling)

This leads to the haematological changes present in CML

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17
Q

Treatment of CML?

A

Tyrosine kinase inhibitors, e.g: Imatinib

18
Q

Types of BCR-ABL1 -ve myeloproliferative disorders?

A

Polycythaemic rubra vera (PRV)

Essential thrombocythemia (ET)

Idiopathic myelofibrosis (IMF)

Others

19
Q

Clinical features common to MPD?

A

Often asymptomatic

Increased cellular turnover:
• Gout
• Fatigue
• Weight loss
• Night sweats

Symptoms/signs due to splenomegaly:
• Early satiety
• Abdominal mass
• Pain

Marrow failure, due to fibrosis or leukaemic transformation (lower with PRV and ET)

Thrombosis (arterial or venous):
• TIA
• MI
• Abdominal vessel thrombosis
• Claudication
• Erythromelalgia (sensation of heat in hands and feat)
20
Q

What is PRV?

A

High Hb/Hct accompanied by erythrocytosis (a true increase in red cell mass

Can have excessive production of other lineages

21
Q

What must PRV be distinguished from?

A

Secondary polcythaemia, e.g:
• Chronic hypoxia (COPD, sleep apnoea)
• Smoking
• Epo-secreting tumour

Pseudopolycythaemia (reduced plasma volume):
• Dehydration
• Diuretic use
• Obesity

22
Q

Clinical features of PRV?

A

All those common to MPD

Headache, fatigue, plethoric appearance (due to increased blood viscosity)

Itch:
• Aquagenic pruritus is itch on exposure to warm water (very characteristic)

23
Q

Ix for polycythaemia)

A

Hx (rule out features suggestive of a secondary polycythaemia)

Examination (splenomegaly, etc)

Ix for secondary / pseudo causes, e.g: CXR, O2 sats, ABGs

FBC, blood film

JAK2 mutation status; if this is -ve, it is unlikely to be PRV (present in 95%)

Infrequent tests:
• Epo levels
• Bone marrow biopsy

24
Q

Why does a JAK2 mutation cause PRV?

A

JAK2 is a kinase; mutation in the gene results in a loss of auto-inhibition

There is activation of erythropoiesis in the absence of the ligand

25
Q

Treatment of PRV?

A

Venesect until Hct is <0.45

Aspirin

Cytotoxic oral chemotherapy (hydroxycarbamide)

26
Q

What is essential thrombocythemia (ET)?

A

Uncontrolled production of abnormal platelets

As platelet function is abnormal:
• Thrombosis
• Acquired von Willebrand disease (can occur at high levels) causes bleedinglevels

27
Q

Clinical features of essential thrombocythemia?

A

All clinical features common to MPD, part. vaso-occlusive complications, e.g: toes

Bleeding; risk is unpredictable, esp. at surgery

28
Q

What does a thrombocytosis with abnormally large platelets indicate?

A

That the thrombocytosis is not reactive

29
Q

Diagnosis of ET?

A

Exclude reactive thrombocytosis, e.g: blood loss, inflammation, malignancy, iron deficiency

Exclude CML

Genetics:
• JAK2 mutations (50%)
• CALR (calreticulin) may be mutated in those without mutant JAK2
• MPL mutations

If all are -ve, bone marrow biopsy (increased platelet precursors, with the megakaryocytes clustering together)

30
Q

Treatment of ET?

A

Anti-platelet agents (do not reduce production):
• Aspirin

Cytoreductive therapy to control proliferation:
• Hydroxycarbamide
• Anagrelide
• Interferon alpha

31
Q

Sub-types of myelofibrosis (MF)?

A

Idiopathic (AKA agnogenic myeloid metaplasia)

Post-polycythaemia or essential thrombocythemia

32
Q

Features of idiopathic myelofibrosis?

A

Marrow failure (variable degrees)

Bone marrow fibrosis, with no secondary fibrosis

Extremedullary haematopoiesis of the liver and spleen (myelofibrosis is a classic cause of massive splenomegaly)

Blood film:
• LEUKOERYTHROBLASTIC
• Teardrop-shaped rbcs in peripheral blood

33
Q

PC of MF?

A

Marrow failure:
• Anaemia
• Bleeding
• Infections

Splenomegaly:
• LUQ abdominal pain
• Early satiety
• Complications, inc. portal hypertension

Hypercatabolism

Also, the clinical features common to MPD

34
Q

Lab diagnosis of MF?

A

Typical blood film:
• LEUKOERYTHROBLASTIC
•TEARDROP shaped rbcs (poikilocytes)

Dry aspirate (as bone marrow contains fibrosis)

Fibrosis on trephine biopsy

In a proportion of patients, JAK2 or CALR are mutated

35
Q

Causes of a leukoerythroblastic blood film?

A

Reactive, e.g: sepsis (bone marrow stress)

Marrow infiltration

Myelofibrosis

36
Q

Treatment of MF?

A

Supportive care:
• Blood transfusion
• Platelet transfusion
• Antibiotics

Allogeneic stem cells transplantation in a select few (older patients often affected so rarely viable)

Splenectomy (controversial)

JAK2 INHIBITORS (used even if the patient is not JAK2 +ve)

37
Q

Effects of JAK2 inhibitors in MF?

A

Improve spleen size, QoL and potentially survival

38
Q

Most common cause of high blood counts?

A

Reactive causes are more common than MPD

39
Q

Reactive causes of high counts?

A

Granulocytes:
• Infection
• Physiological, e.g: post-surgery, steroids

Platelets:
• Infection
• Iron deficiency
• Malignancy
• Blood loss

Red cells:
• Dehydration, e.g: with diuretics, causes a pseudopolycythaemic
• Secondary polycythaemia, e.g: hypoxia-induced (COPD, sleep apnoea)

40
Q

Compare the complications of high counts due to MPD to high counts due to reactive causes?

A

Reactive causes of high counts are unlikely to be associated with the complications of MPD, like thrombosis

Year 3 Clinical (100 decks)

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