Myeloproliferative Flashcards by Martha Innes

What are myeloproliferative neoplasms?

Group of disorders characterised by clonal expansion of a stem cell population
Increased production of myeloid cells with relatively preserved maturation

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What will a blood film be like in myeloproliferative neoplasms?

Polymorphic - wide variety of cells at different stages of maturation
Hypercellular

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What is proliferation of red cells?

Polycythaemia vera

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What is proliferation of white cells?

Chronic myeloid leukaemia

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What is proliferation of platelets?

Essential thrombocythaemia

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What is proliferation fo fibroblasts?

Primary myelofibrosis

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Which myeloproliferative neoplasm is BCR-ABL1 positive?

CML

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What is the Philadelphia chromosome associated with?

CML

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When should you consider myeloproliferative neoplasms?

Splenomegaly
Thrombosis in an unusual place
High granulocyte count (eosinophilia, basophilia, neutrophilia)
High red cell count/Hb
High platelet count
No reactive cause

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What is the mean age of diagnosis of myeloproliferative neoplasms?

65 (but can be much younger)

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What are the general features of myeloproliferative neoplasms?

Can be asymptomatic
Increased cellular turnover
Splenomegaly
Marrow failure
Thrombosis

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What are the clinical features of increased cellular turnover?

Gout
Fatigue
Weight loss
Sweats

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What are the clinical features of splenomegaly?

Early satiety

LUQ pain

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What are the clinical features of thrombosis in myeloproliferative neoplasms?

Arterial or venous (TIA, MI, abdominal vessel thrombosis, claudication)
Erythromelelgia - paint nd redness in hands and feet

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What is polycythaemia?

Increase in red cells

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What is the pathophysiology of polycythaemia vera?

Increased red cell mass due to increased production

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What should polycythaemia vera be distinguished from?

Secondary polycythaemia (reactive)
Pseudopolycythaemia

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What are causes of secondary (reactive) polycythaemia?

Chronic hypoxia (COPD, smoking)
Increased erythropoietin production (renal or hepatic carcinoma)

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What is pseudo-polycythaemia?

Relative increase in Hb due to plasma cell depletion

What are causes of pseudo-polycythawmia?

Alcohol
Obesity
Dehydration
Diuretic therapy

What mutation causes polycythaemia vera, and how?

JAK2
A tyrosine kinase that controls erythropoiesis by auto-inhibition
Mutation causes loss of auto-inhibition and stimulation of red cell production in the absence of stimuli?

How common are JAK2 mutations in polycythaemia vera?

Present in over 95% of patients with polycythaemia vera

What is the presentation of polycythaemia vera?

Hyperviscocity
- lethargy
- confusion
- headache
- dizziness
- visual disturbance
Splenomegaly
- abdo pain and distension
- gout
Aquagenic pruritus (itch after warm shower/bath)
Erythromelelgia
Facial plethora

What do investigations show in polycythaemia vera?

JAK2 mutation positive
Bloods - high Hb, high reticulocytes, high platelets
Erythroid hyperplasia on marrow biopsy
Neutrophil alkaline phosphatase score increased

What investigations can be done in polycythaemia to check for secondary/pseudo causes?

CXR O2 saturation Arterial blood gases Drug history

What is the aim of management of polycythaemia vera?

Reduce risk of thrombosis

What is the management of polycythaemia vera?

Low risk - venesection, aspirin | High risk - hydroxycarbamide, aspirin

What does high risk mean in polycythaemia vera?

>60 | Previous thrombosis

What is essential thrombocythaemia?

Uncontrolled increase in platelets

What is the pathophysiology of essential thrombocythaemia?

Uncontrolled proliferation of megakaryocytes causing increased production of abnormal platelets Causes thrombosis tendance At high levels can cause bleeding due to acquired von Willebrand disease as vWF is absorbed into abnormal platelets, reducing circulating vWF levels

What mutations can cause essential thrombocythaemia?

JAK2 (not as common as PV) | CALR

What are other causes of thrombocythaemia?

``` Bleeding Infection Malignancy Trauma/surgery Splenectomy nad hyposplenism ```

What is the presentation of essential thrombocythaemia?

MPN common clinical features (thrombosis, marrow failure, high cellular turnover, splenomegaly) Vaso-occlusive complications Bleeding

What can thrombosis commonly cause in essential thrombocythaemia?

Stroke, DVT/PE Recurrent miscarriages Digital ischaemia (gangrene fingers and toes) Erythromelalgia (erythema and shooting pain in limbs) Microembolisms

What do investigations show in essential thrombocythaemia?

Thrombocytosis Marrow biopsy - hypercellular, megakaryocytes Genetics - JAK2, CALR

What is the management of essential thrombocythaemia?

Lifestyle factors to reduce thrombosis risk Aspirin Hydroxycarbamide if high risk for thrombosis

What is hydroxycarbamide, how does it work and what are other similar options?

Cytoreductive therapy to control proliferation | Other options: anagrelide, interferon alpha

What is idiopathic myelofibrosis?

Megakaryocyte proliferation causing stimulation of fibroblasts

What is the pathophysiology of idiopathic myelofibrosis?

Increase in megakaryocytes is associated with increased release of platelet derived growth factor, causing stimulation of fibroblasts and bone marrow fibrosis Fibrosis causes marrow failure, compensated for by extra medullary haematopoiesis in the liver and spleen

What are the key blood film features of idiopathic myelofibrosis?

Leucoerythroblastic film appearance - both myeloid and erythroid precursors in the blood Teardrop shaped RBCs

What is the presentation of idiopathic myelofibrosis?

``` Non-specific Fever, night sweats Abdominal pain in LUQ Symptoms of marrow failure (bleeding, infections, anaemia) Massive splenomegaly ```

What do investigations show in idiopathic myelofibrosis?

Bloods - low Hb, high WCC, high platelets Bone marrow biopsy - marrow fibrosis Genetics - JAK2, CALR, MPL

What are the possible mutations in idiopathic myelofibrosis in order of most to least common?

JAK2 > CALR > MPL

How many people with idiopathic myelofibrosis have no mutation?

10% are triple negative

What is the management of idiopathic myelofibrosis?

Supportive care as required for marrow suppression (blood transfusion, platelets, antibiotics, allopurinol if hyperuricaemia) Active treatment - bone marrow transplant - ruxolitinib (JAK2 inhibitor)