Chronic Myeloproliferative Disorders and chronic myeloid leukaemia Flashcards
What are chronic myeloproliferative disorders? Give examples
Clonal stem cell disorders of the bone marrow which can are malignant :
1) Polycythaemia Vera
2) Essential Thrombocytosis
3) Idiopathic Myelofibrosis
What are the 3 types of cell the bone marrow stem cells differentiate into?
1) Granulocytes (neutrophils, eosinophils, basophils)
2) ertythrocytes
3) Megakaryocytes (platelets)
What chronic myeloproliferative disorder causes increased RBCs, with increased neutrophils, and increased platelets?
Polycythaemia Vera
Increased platelets is a sign of what chronic myeloproliferative disorder?
Thrombocythaemia
In what chronic myeloproliferative disorder is Variable cytopenia (lowered blood cell count) and a large spleen seen.
Myelofibrosis
Which chronic myeloproliferative disorder causes splenomegaly?
1) Myelofibrosis
2) Polycythaemia Vera
What is myelofibrosis?
Scarring in the bone marrow that leads to severe anaemia, weakness and an enlarged liver and spleen.
What is the peak age of Polycythaemia?
50-70 years
What is polycythaemia Vera?
Polycythaemia Vera is caused by a mutation in JAK2 gene which causes the bone marrow makes too many RBCs (also sometimes WBCs and Platelets.)
What chronic myeloproliferative disease are are the following symptoms associated with?
- itching
- plethoric face (red face)
- Head ache
- malaise
- tinnitus
- peptic ulcer
- gout
- gangrene of toes
Polycythaemia Vera
What chronic myeloproliferative disorder are the following signs associated with?
- Plethora (redness)
- Engorged retinal veins
- splenomegaly
Polycythaemia Vera
What are the causes of secondary polycythaemia?
1) central hypoxic processes:
- chronic lung disease
- right to left heart shunts
- carbon monoxide poisoning
- smoking
- high altitude
2) Renal disease
- Erythropoeitin producing tumours
- drug associated
- congenital
What is a diagnostic factor of Polycythaemia Vera?
Persistent increased Hb/hct > 0.5
What is Persistent increased Haemoglobin / haemocrit >0.5 a diagnostic sign of?
Polycythaemia Vera
What is a Phenylalanine for valine mutation at 617 in protein (V617F) associated with?
Phenylalanine for valine mutation at 617 in protein (V617F) is a JAK2 mutation.
If found in peripheral blood DNA this is diagnostic of a myeloproliferative disorder.
What is the treatment for polycythaemia vera?
- Venesections (removal of blood)
- Aspirin 75mg daily
What are the following causes of (Essential thrombocytosis or reactive thrombocytosis)?
1) surgery
2) Infection
3) Inflammation
4) Malignancy
5) Iron def
6) Hyposplenism
7) Haemolysis
8) Drug incudes
9) rebound post chem
REACTIVE thrombocytosis
50% of essential thrombocytosis is caused by a JAK2 mutation. What mutation causes 45% of essential thrombocytosis?
CALR mutation
calreticulin mutation affect cell signalling
how is essential thrombocytosis treated
antiplatelet treatment:
Aspirin 75mg daily
Cytoreduction
What is the prognosis of thrombocytosis?
20 year survival
what chronic myelpproliferative disease are the following presenting features a sign of?
- pancytopenia (RBC, WBC and platelet deficiency)
- B symptoms
- massive spenomegaly
Myelofibrosis
Describe the memory aid CHICAGO that is used for causes of Splenomegaly?
C - cancer
H - Haematological (Myelofibrosis)
I - Infection (Schistosomiasis, malaria)
C -Congestion (liver disease, portal hypertension)
A-Autoimmune (haemolyisis)
G - Glycogen storage disorders.
O - other (amyloid deposition)
What are the following characteristics associated with?
- Leucocytosis (increased WBC)
- Leucoerythroblastic blood picture
- Anaemia
- Splenomegaly
Chronic myeloid leukaemia
What are some of the syptoms of chronic myeloid leukaemia?
- Abdo pain (splenomegaly / splenic infarction)
- fatigue (anaemia)
- venous occlusion (in retinal vein, DVT)
- gout (hyperyricaemia)
What drug does BCR-ABL mutations confer resistance to?
Imatinib
What disorder is fined by the t(9;22) translocation and driven by BCR-ABL fusion tyrosine kinase?
Chronic Myeloid Leukaemia
What are the risk factors of thrombosis?
1) Age > 60yrs
2) Hypertension
3) Diabetes
4) Platelets > 1500