8: Myeloproliferative disorders Flashcards
What is the myeloid lineage?
Granulocyte
Red blood cell
Platelet
lineages
What is the difference between chronic myeloid leukaemia and acute myeloid leukaemia?
Differentiation and maturation PRESERVED in chronic disease
Which mutation is associated with chronic myeloid leukaemia?
Philadelphia chromosome
CML is BCR-ABL1 (positive / negative).
CML = BCR-ABL1 positive
What is a normal, secondary cause for a rise in blood components?
Reactive change
in response to infection usually
Which blood components can increase in myeloproliferative disorders?
RBCs
Platelets
White cells (basophils/eosinophils is especially significant)
Which organ can enlarge in myeloproliferative disorders?
Spleen
Increased cell breakdown
What is a risk seen in hyperviscosity secondary to raised cell counts?
Thrombosis
Chronic ___ causes a secondary polycythaemia - why?
Chronic hypoxia (e.g sleep apnoea, COPD)
Persistent EPO release by the kidneys
What is the course of untreated chronic myeloid leukaemia?
1. Chronic phase for 3-5 years, maturation intact
2. Accelerated phase - maturation starting to fail
3. Blast crisis and death - more closely resembling an acute leukaemia
What are some clinical features of CML?
Hyperviscosity symptoms
Hypermetabolism - cachexia
Splenomegaly
Gout
How is suspected CML investigated?
FBC
Bone marrow biopsy
An increase in which specific blood components strongly suggest CML?
Eosinophilia
Basophilia
not normally found in large numbers
What might be misdiagnosed as CML based on blood changes?
Reactive changes due to infection
Which genetic mutation is commonly found in CML?
Unbalanced chromosome 22 translocation
‘BCR-ABL’ gene on the Philadelphia chromosome
BCR-ABL mutations on the Philadelphia chromosome affect which protein?
Tyrosine kinase
What is a tyrosine kinase inhibitor used to treat CML?
Imatinib
Imatinib is a ___ ___ inhibitor which massively increases life expectancy in which disease?
tyrosine kinase inhibitor
CML
CML is positive for which mutation?
BCR-ABL1
Philadelphia chromosome (22)
What is erythromelalgia?
Which group of diseases is it a feature of?
Hot, swollen, red, painful digits due to blood stasis
Myeloproliferative diseases
Caused by HYPERVISCOSITY of blood
In which disease does haemoglobin and haematocrit increase abnormally?
Polycythaemia
What is primary polycythaemia called?
Polycythaemia rubra vera
Which genetic mutation is implicated in polycythaemia rubra vera?
JAK2
What causes secondary polycythaemia?
Chronic hypoxia
EPO-secreting renal tumours
What is pseudopolycythaemia?
Appearance of raised Hb / haematocrit which is actually due to a reduced plasma volume
What causes pseudopolycythaemia?
Dehydration / Diuretic therapy
Obesity
Alcohol excess
Pseudopolycythaemia and ___ polycythaemia mean the same thing.
apparent polycythaemia
What are some symptoms of primary polycythaemia?
Plethora
Itch (caused by warm water)
Hyperviscosity symptoms
Which genetic mutation is screened for in polycythaemia rubra vera?
JAK2
JAK2 mutations are seen in 95% of patients with ___ ___ ___.
polycythaemia rubra vera (primary)
What process is uninhibited it patients with polycythaemia rubra vera?
Erythropoiesis
What are some investigations for suspected secondary polycythaemia?
CXR
Medication history - e.g testosterone
EPO levels
Bone marrow biopsy
How is polycythaemia rubra vera treated?
Venesection until haematocrit is < 0.45
Aspirin (anti-platelet - deactivates platelets, reducing hyperviscosity of blood)
Cytotoxic drugs e.g hydroxycarbamide - kills off excess cells
Polycythaemia rubra vera can lead to thrombosis in some patients.
How is this prevented?
Aspirin
In addition to venesection, how can Hb / haematocrit be reduced in polycythaemia rubra vera?
Cytotoxic drugs e.g hydroxycarbamide
In which disease is idiopathic platelet excess seen?
Essential thrombocythaemia
Essential thrombocythaemia can cause both thrombosis and abnormal bleeding.
Why?
Thrombosis - excess of platelets
Abnormal bleeding - platelets mop up vWF, causing acquired von Willebrand’s disease
Is anaemia a feature of essential thromocythaemia?
No
Don’t confuse ET for thrombocytosis caused by reactive change, in which patient would be anaemia
RBCs and platelets are derived from the same progenitor cells.
What are some causes of reactive thrombocytosis which may cause a blood picture similar to essential thrombocythaemia?
Blood loss
Haemolysis
Inflammation
Malignancy
How is essential thrombocythaemia treated?
Aspirin (anti-platelet drug)
Chemotherapy to suppress proliferation in some patients
Which myeloproliferative disorder causes progressive fibrosis of the bone marrow?
Myelofibrosis
Myelofibrosis can occur secondary to which other MPDs?
Polycythaemia
Essential thrombocythaemia
What blood film appearance, caused by leakage of progenitor cells into the blood, is seen in myelofibrosis?
Leukoerythroblastic blood film
Which shape of RBC is seen in myelofibrosis?
Teardrop cells
What are the main clinical features of myelofibrosis?
Pancytopaenia - anaemia, abnormal bleeding, increased infection risk
Splenomegaly
Hypercatabolism - cachexia
Teardrop cells on a blood film
What are the two blood film appearances to look out for in myelofibrosis?
Leukoerythroblastic film
Teardrop cells
What are some causes of a leukoerythroblastic blood film?
Reactive change as in infection
Bone marrow infiltration
Myelofibrosis
What is the appearance of myelofibrosis on a bone marrow biopsy?
Fibrosis - collagen fibres
How is myelofibrosis treated?
Supportive management of pancytopaenia (blood transfusion, platelet transfusion, prophylactic antibiotics)
Young, fit patients receive stem cell transplants
Most raised blood counts will be caused by ___ change.
reactive change
infection
Which supplement, often taken by bodybuilders, can cause secondary polycythaemia?
Testosterone
Patients with polycythaemia rubra vera have blood taken until their haematocrit is below which threshold?
< 0.45
0.45 means that 45% of your blood sample is made up of red cells
