Myeloproliferative Disorders Flashcards by Kerry Hendrie

What are myeloproliferative disorders (MPD)?

Haemopoietic stem cell disorders involving increased production with preservation of maturation

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How are myeloproliferative disorders (MPD) different from acute leukaemia?

Maturation is relatively preserved

Mature cells seen on film, whereas in leukaemia they are monomorphic nucleated cells (‘blasts)

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What are the 2 groups/sub-types of myeloproliferative disorders?

BCR-ABL1 negative

BCR-ABL2 positive

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Which MPD is BCR-ABL2 positive?

Chronic myeloid leukaemia

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Which MPDs are BCR-ABL2 negative?

Essential thrombocythaemia
Polycythaemia rubra vera
Idiopathic myelofibrosis

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When should an MPD be considered?

High granulocyte count (chronic myeloid leukaemia)
High red cell count (polycythemia rubra vera)
High platelet count (thrombocythaemia)
Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place

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What happens in chronic myeloid leukaemia?

Excess proliferation of myeloid cells (granulocytes, platelets)
3-5 years chronic phase followed by “blast” crisis akin to acute leukaemia which can be fatal

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What would the blood film of someone with chronic phase CML look like?

Lots of mature neutrophils

Increased primitive cells

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What would the blood film of someone with accelerated phase CML look like?

Some neutrophils

Increased primitive cells

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What would the blood film of someone with blast crisis in CML look like?

Monomorphic nucleated blasts (myelocytes)

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List some clinical features of chronic myeloid leukaemia

Asymptomatic
Splenomegaly (fatigue, LUQ pain)
Hypermetabolic symptoms (sweats, fever)
Weight loss
Bone pain
Gout
Miscellaneous (priapism, visual blurring)

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Describe the bone marrow of a patient with CML

Increased myelocytes and eosinophils

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Hb may be normal in chronic myeloid leukaemia. True/False?

True

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Which chromosomes are affected in chronic myeloid leukaemia? What is the genetic change and resultant protein?

“Philadelphia” chromosomes
9 and 22 translocation
Produces tyrosine kinase which causes abnormal phosphorylation and production of BCR-ABL1

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List some clinical features of BCR-ABL1 negative myeloproliferative disorders

Asymptomatic
Increased cellular turnover (gout, fatigue, weight loss, sweats)
Signs due to splenomegaly
Marrow failure (fibrosis or leukaemic transformation)
Thrombosis (arterial or venous) e.g. TIA, MI

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What is erythromelaegia?

It is characterized by intense, burning pain of affected extremities, severe redness (erythema), and is associated with myeloproliferative disorders

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What is polycythaemia rubra vera?

High haemoglobin/haematocrit accompanied by erythrocytosis (overproduction of red cells) but can have excessive production of other lineages

How is polycythaemia rubra vera distinguished from secondary polycythaemia?

Secondary polycythaemia is caused by smoking, chronic hypoxia, erythropoietin-secreting tumours

How is polycythaemia rubra vera distinguished from pseudo-polycythaemia?

Pseudo-polycythaemia is caused by dehydration, diuretic therapy, obesity
i.e. plasma volume has shrunk which makes it seem like Hb is high but it is not

List some clinical features of polycythaemia rubra vera

Headache
Fatigue
Itch (aquagenic puritis)
MPD features

What is aquagenic puritis?

Itch worse on exposure to warm water

List investigations for polycythaemia

History (triggers of secondary polycythaemia)
Examination e.g. splenomegaly
FBC, film
Investigation for secondary/pseudo causes (CXR, O2 sats/ABG, drug history)
Bone marrow biopsy

Splenomegaly will not be present in secondary polycythaemia. True/False?

True

Which gene mutation is important to investigate as a diagnostic tool in polycythaemia?

JAK2 - a kinase mutation present in 95% patients

Activation of erythropoeisis in absence of ligand

How is polycythaemia rubra vera treated?

Venesection until haematocrit less than 0.45 Aspirin Cytotoxic oral chemotherapy e.g. hydroxycarbamide

What is essential thrombocythaemia?

Uncontrolled production of abnormal platelets, resulting in abnormal platelet function

What other clinical features, in addition to those common to MPD is present in patients with essential thrombocythaemia?

Thrombosis (abnormal platelet function) | Bleeding (unpredictable risk especially at surgery)

What gene mutations can be present in essential thrombocythaemia?

JAK2 CALR MPL

What is the characteristic bone marrow appearance of a patient with essential thrombocythaemia?

Lots of big platelets | Clustering of megakaryocytes

How is essential thrombocythaemia treated?

Aspirin | Cytoreductive therapy to control proliferation (hydroxycarbamide, anagrelide, IFNalpha)

What is idiopathic myelofibrosis?

Proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis of the bone marrow

List clinical features of myelofibrosis, other than those common to MPD

``` Marrow failure (anaemia, bleeding, infection) Extramedullary haematopoeisis (splenomegaly) Hypercatabolism (weight loss, cachexia) ```

Describe the appearance of a blood film in myelofibrosis

Leucoerythroblastic Teardrop-shaped RBC's in peripheral blood (RBCs squeezing out of a fibrotic bone marrow)

What is meant by a leucoerythroblastic film?

Erythroblast, red cell precursor, and myelocyte, granulocyte precursors in peripheral blood

List causes of a leucoerythroblastic film

Reactive (sepsis) Marrow infiltration Myelofibrosis

List diagnostic tests for myelofibrosis

Blood film Dry aspirate Fibrosis on trephine biopsy JAK2 or CALR mutation in a proportion

List treatment options for myelofibrosis

Supportive care (blood transfusion, platelets, abx) Allogenic stem cell transplantation in young Splenectomy JAK2 inhibitors (improve spleen size and QoL)

Reactive causes of high cell counts are more common than myeloproliferative disorders. True/False?

True

List some reactive causes of raised granulocytes

Infection Post-surgery Steroids

List some reactive causes of raised platelets

``` Infection Iron deficiency Malignancy Blood loss Post-splenectomy ```

List some reactive causes of raised red cells

Dehydration Diuretics Secondary polycythemia (hypoxia etc.)