Myeloproliferative Disorders Flashcards
What are myeloproliferative disorders?
A group of conditions characterized by clonal proliferation of one or more haemopoietic component i.e. increased production of mature cells
How are Myeloproliferative disorders grouped and which conditions are in each group?
Philidelphia -ve: Polycythaemia Vera, Essential Thrombocythaemia, Primary Myelofibrosis
Philidelphia +ve: Chronic Myeloid Leukaemia
What are the Primary Causes of True Polycythaemia?
Polycythaemia Vera, Familial Polycythaemia
What are the Secondary Causes of True Polycythaemia?
Appropriately raised EPO: high altitude, hypoxic lung disease, cyanotic heart disease, high affinity Hb
Inappropriately raised EPO: renal disease (cysts, tumours, inflammation), uterine myoma, liver and lung tumours
What is Relative (Psuedo) Polycythaemia? what are the causes?
Normal RBC, but reduced plasma volume
Causes: burns, vomiting, diarrhea, smoking, diuretics, obesity (anything that ‘dries you out’)
The main symptoms of PRV is hyperviscosity and hypervolaemia, how can this manifest clinically?
Blurred vision, headache, fatigue, dyspnoea, plethoric (red nose), thrombosis and stroke, retinal vein engorgement, erythromyalagia, splenomegaly
An increase of what inflammatory substance in PRV cause aquagenic pruritis? What else can it cause?
Histamine.
Peptic Ulcers
What point mutation is associated with PRV
JAK2 (V617F)
What investigations should be ordered if you suspect PRV and what would a positive result show?
Full Blood Count: Hb, HCT, platelets, WCC, EPO
Hb and HCT will be very high, platelets and WCC can also be raised.
Low serum EPO.
NB. PRV is normally an incidental finding on routine blood checks
What are the treatments for PRV?
Venesection
Hydroxycarbamide (maintenance)
Aspirin (keep platelets under 400)
Aim of treatment is to reduce the viscosity of blood
What is myelofibrosis?
Myeloproliferation causes fibrosis of BM or replacement with collagenous tissue. Can be primary (idiopathic) or secondary.
What can cause secondary myelofibrosis?
PRV, Essential Thrombocytopenia, leukaemia… probably other things, but these are the main 3
What causes the splenomegaly in myeloproliferative disorders?
Increased haemopoesis in the BM causes it to become overrun, so the spleen and liver begin to take over haemopoesis
What will you see on a myelofibrotic blood film?
Blood film: tear drop poikilocytes (dacrocytes), leukoerythroblasts (primitive cells), giant platelets, circulating megakaryocytes
What would a myelofibrotic bone marrow biopsy show?
increased collagen fibrosis, prominent megakaryocyte hyperplasia and clustering with abnormalities, new bone formation
How is a LP of someone with myelofibrosis often described?
“dry tap”
What are the treatments for myelofibrosis?
Support with blood products
Splenectomy - for symptomatic relief
Hydroxycarbamide (cytoreductive therapy), thalidomide, steroids, SCT
New = Ruxolotinib (JAK2 inhibitor)
What are the clinical features of Myelofibrosis?
hepatomegaly, massive SPLENOMEGALY, weight loss
Pancytopenia symptoms: anaemia, fatigue, easy bruising, frequent fevers etc.
Can present with Budd-Chiari Syndrome
In which MPD do megakaryocytes dominate the BM (increased platelets)?
Essential Thrombocythaemia (Thrombocytosis)
What are the clinical features of essential thrombocythaemia?
Venous are arterial thrombosis (stroke and MI), gangrene, and haemorrhage, erythmelalgia (red hands and feet), splenomegaly, dizziness, headaches, visual disturbances
What would a patients blood tests, blood films and bone marrow show if they had essential thrombocythemia?
Platelet count over 600
Film: large platelets and megakaryocyte fragments
BM: increased megakaryocytes
What is the treatment for ET?
Aspirin, Anagrelide (reduces formation of plts from megakaryocytes), Hydroxycarbamide (antimetabolite, only used if plt count is very high)
What is the prognosis of ET?
Often have normal life span
Around 5% will have leukaemic transformation after 10 years.
What is the prognosis of Myelofibrosis and what s the average age of incidence.
Prognosis: 3-5 years
Age of incidence: around 70yo
