Polycythaemia Vera - see

Question 1

What is polycythaemia vera

Answer 1

Myeloproliferative disorder caused by clonal proliferation of marrow stem cell -> increase RCC volumes, neutropgils and platelets

Question 2

What genetic cause of PCV

Answer 2

JAK2 mutation 95%
JAK2 V617F mutation
Rarer - JAK2 exon 12 mutations

Question 3

How does JAK2 cause PCV

Answer 3

JAK2 codes for tyrosine kinase -> haematopoietic growth factors incl EPO
Activation of AJK-STAT signalling pathwya -> proliferation and survival of haematopoietic progenitor cells independednt of EPO

Question 4

Features of PCV

Answer 4

Hyperviscosity - VTE risk
Pruritis - after hot bath - aquagenic
Splenomegaly
Haemorrhage
Headaches, migraine, blurred vision
Plethoric appearance
HTN 1/3 patients
fatigue

Question 5

Investigations PCV

Answer 5

FBC
JAK2 mutation
Serum ferritin
U+Es, LFTs
Coag study

Question 6

Further investigations if JAK2 mutation negative and no obscious causes sytmpsm

Answer 6

RBC mass
ABG O2
Abdo US
Serum EPO
Bone marrow aspirate and trephine
Cytogenic analysis
Erythroid burst forming unit - BFU-E culture

Question 7

JAK positive PCV criteria

Answer 7

A1 - High haematocrit
OR
Raised RBC mass - >25% above predicted
A2 - Mutation in JAK2

Question 8

High haematocrit

Answer 8

> 0.52 in men
0.48 in women

Question 9

Criteria for JAK negative PCV

Answer 9

Raised RBC >25% predicted OR haematocrit
A2 - absence of mutation JAK2
A3 - no secondary cause of erythrocytosis
A4 - palpable splenomegaly
A5 - acquired genetic abnormality in haemopoietic cells
B1 - thrombocytosis >450
B2 - Neutrophil leucocytosis
B3 - Radiological evidence splenogemay
B4 - endogenous erythroid colonies or low serum EPO

Question 10

Management of PCV

Answer 10

VENESECTION
aspirin adn reviw CVS risk factors
hydroxyurea
Phosphorous 32 therpay

Question 11

Prognosis PCV

Answer 11

THrombotic events most common cause death
5-15% -> myelofibrosis
5-15% -> AML (increased wrisk w chemo)

Question 12

What would low ESR and raised leukocyte ALP suggest

Answer 12

polycythaemia vera

Question 13

Types of polycythaemia

Answer 13

Relative eg pseudo - reduction in plasmavolume eg dehydration, alcohol, diuretics
True - red cell mass increased

Question 14

What conditions are PCV related to

Answer 14

Resp disease eg hypoxic resp failure, OSA, smkooing
Cyanotic cardiac disease
Abnormal EPO production (renal carcinomas, hepatacellular carcinomas) or high altitidue
Endocrine - testosterone, anabolic steroids, doping

Question 15

Goal for venesection

Answer 15

<0.45 - avoid iron!

Question 16

When do you cytoreduction rather than venesect

Answer 16

> 65 years
Prev VTE
other CVS risk factors

Question 17

Cytoreduction options

Answer 17

Hydroxycarbamide
Interferon, busulfan