Polycythaemia & Myelofibrosis Flashcards
What is polycythaemia?
Rise in RBCs
What is a 1ary cause of polycythaemia?
Polycythaemia rubra vera
What are some 2ary causes of polycythaemia? (4)
1) COPD
2) Altitude
3) Obstructive sleep apnoea
4) Excessive EPO:
- cerebellar haemangioma
- hypernephroma
- hepatoma
- uterine fibroids
What are 2 causes of relative polycythaemia?
1) dehydration
2) stress: Gaisbock syndrome
What is polycythaemia vera?
A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume.
This is often accompanied by overproduction of neutrophils and platelets.
What is a myeloproliferative disorder?
A group of rare disorders of the bone marrow that cause an increase in the number of blood cells
What mutation is present in approx 95% of patients with polycythaemia vera?
JAK2 mutation
Peak age of incidence of polycythaemia vera?
60-70 y/o
What does the JAK2 gene encode for?
A non-receptor tyrosine kinase involved in EPO.
Mutation results in activation of this pathway –> increased proliferation and survival of hematopoietic progenitor cells, independent of EPO stimulation.
What is the hallmark of polycythaemia vera?
Increased production of RBCs
Why can patients with polycythaemia vera also present with raised WCC and raised platelets?
As the JAK2 mutation also influences the proliferation of other myeloid progenitor cells.
How can PV affect viscosity of blood?
Overproduction of blood cells results in increased blood viscosity.
Complications of hyperviscosity seen in PV?
Increased risk of thrombotic events:
1) DVT
2) PE
3) Arterial thrombosis e.g. stroke, MI
Complications of the increased blood volume seen in PV?
Venous congestion and engorgement of organs:
- hepatomegaly
- splenomegaly
Clinical features of PV?
1) Hyperviscosity
2) Pruritus, typically after a hot bath
3) Splenomegaly
4) Haemorrhage (secondary to abnormal platelet function)
5) Plethoric appearance
6) HTN in a third of patients
What is the diagnostic criteria for PV? (2)
1) High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)
2) Mutation in JAK2
Diagnosis requires BOTH criteria to be present.
Mx of PV?
1) Aspirin
2) Venesection –> 1st line
3) Hydroxyurea
4) Phosphorus-32 therapy
Mx of PV with hydroxyurea carries a slightly increased risk of what?
2ary leukaemia
3 key complications of PV?
1) Thrombotic events
2) Myelofibrosis (5-15% of patients progress)
3) Acute leukaemia (5-15% of patients progress & risk increased with chemotherapy treatment)
What is myelofibrosis?
A rare haem disorder where bone marrow is replaced with collagen and becomes fibrosed.
This results in:
- haematological abnormalities
- profound fatigue
- massive splenomegaly
- extramedullary haematopoiesis
Mean survival of myelofibrosis?
6 years
Peak age of incidence of myelofibrosis?
60-70y
Features of myelofibrosis?
1) Severe fatigue
2) Hepatosplenomegaly
3) B symptoms (20%
4) Signs of anaemia
5) Thromboembolic events (2ary to thrombocytosis)
6) Unexplained bleeding (2ary to thrombocytopenia)
Approx 20% patients may be asymptomatic.
Where are the 2 most common sites of extramedullary haematopoiesis in myelofibrosis?
Liver & spleen
What may a FBC show in myelofibrosis?
Pancytopenia
What may a peripheral blood smear show in myelofibrosis?
Teardrop shaped red cells
What will a bone marrow biopsy show in myelofibrosis?
fibrosis and abnormal megakaryocytes
What is the most common mutation associated with myelofibrosis?
JAK2
Give an example of a JAK2 inhibitor?
Ruxolitinib
What is the most common cause of death in myelofibrosis?
Following a transformation to acute myeloid leukaemia.
What leukaemia can myelofibrosis transform into?
AML
