When Haempopoiesis Goes Wrong Flashcards
What is a Myoproliferative Neoplasm/ Disorder
What are the 4 major types and how do do they arise generally
A disease in the bone marrow in which excess cells are produced
Polycythaemia Vera
Essential thrombocytothaemia
Primary myelofibrosis
Chronic myeloid leukaemia
Arise from mutations in myeloid precursors
Describe the genetic basis of myeloproliferative disorders
Mutation in Janus Kinase 2 (JAK 2 gene), (cytoplasmic Tyrosine Kinase) leading to increased proliferation and survival of haematopoietic precursors
What is polycythemia
Compare the 2 types
When Haematocrit exceeds 52% in males/ 48% in females
Relative: Decreased plasma volume
Absolute: Increase in number of RBCs
Compare the 2 types of causes of Absolute Polycythaemia
Which type is Polycythaemia Vera
What are 2 types of causes of the other type? Name 2 causes from each
Primary: Abnormality originates in bone marrow
Secondary: Increased EPO levels
Polycythaemia Vera= Primary
Physiological response: High altitude, Chronic lung disease
Abnormal production: Renal tumour, artery stenosis
Identify 5 clinical features of Polycythaemia Vera
What may it transform into
Thrombosis Haemorrhage Splenomegaly Gout Itching
Myelofibrosis/ acute leukaemia
What are 2 treatments for Polycythaemia Vera
Venesection to keep Hct below 45%
Aspirin (Anti-platelet effects)
What is Thrombocytosis, compare the 3 types
Which type is essential thrombocytothaemia
Excess platelets in blood
Primary: Myeloproliferative neoplasm in marrow
Secondary: Normal bone marrow response
Redistributional: Redistributed from spleen to blood
Primary
What are 2 causes of Essential Thrombocytothaemia
How is it treated
- Mutation in thrombopoietin receptor
- JAK2 mutation (50% of cases)
Low risk patients: Aspirin
High risk patients: Drugs that reduce platelet count (Hydroxycarbamide)
Identify 5 symptoms of Essential Thrombocytothaemia
- Numbness in extremities
- Thrombosis
- Hearing/ vision disturbances
- Headaches
- Burning pain in hands/ feet
What is Primary Myelofibrosis
What causes it?
What is Secondary Myelofibrosis
A myeloproliferative neoplasm causes scar tissue to build up in bone marrow, stimulating extramedullary haematopoiesis.
Caused by JAK2 mutations
When disease has developed due to Essential Thrombocytothaemia/ Polycythaemia Vera
Identify 4 symptoms of primary myelofibrosis
What can it turn into
Hepatosplenomegaly
Fatigue
Sweating
Weight loss
Leukaemia
Compare acute and chronic leukaemias
Acute: Rapid marrow failure, as many immature blast cells reduce ability to make mature RBCs.
Chronic: Slow to show symptoms, differentiation often occurs
what is Chronic Myeloid Leukaemia associated with, on a chromosomal basis
Outline how this causes Chronic Myeloid Leukemia
Philadelphia chromosome/ translocation which, involves reciprocal translocation between chromosomes 9 and 22
- Philadelphia chromosome
- Causes an oncogenic gene fusion, with tyrosine kinase activity
- -> Proliferation, differentiation and inhibition of apoptosis
What is pancytopenia
What are 2 causes, which is more common
Reduced WBCs, RBCs, Platelets
Reduced production- more common
Increased removal
What are 5 causes of Pancytopenia caused by reduced production
B12/ Folate deficiency Drugs Viruses Marrow fibrosis Idiopathic aplastic anaemia
