Myeloproliferative neoplasms - when haemopoieis goes wrong Flashcards
What are MPNs
Group of diseases of the bone marrow where excess cells are produced arising from genetic mutations in precursors of myeloid lineage in the bone marrow
What are the main types of MPNs
Polycythaemia vera
Essentail thrombocytheaemia
Primary myelofibrosis
Chronic myeloid leukaemia
What is polycythaemia and what are the two types
It is a disease wher the volume percent of erythrocytes in the blood (haematocrit) exceeds 52% (males) or 48% (females)
Absolute polycythaemia - increases in erythrocytes
Relative polycythaemia - decrease in plasma volume
How is polycythaemia characterisated based on its cause
Relative - decreased plasma volume
Absolute - increased RBC number
- Primary - abnormality in the bone marrow
- Secondary - increased levels of EPO
- Physiological response to hypoxia
- Abnormal production
What is polycythaemia vera
Polycythaemia caused by myeloproliferative neoplasm in the bone marrowing causing overproduction of erythrocytes
Caused by mutation in Janus Kinase 2 (JAK2) gene
Cells with mutation in JAK2 survive longer and proliferate continuously
What are the clinical features of polycythaemia vera
Result from blood being thicker and include:
Thrombosis
Haemorrhage
Headache and dizziness
Plethora
Burning pain in hands or feet
Pruritus
Splenic discomfort - splenomegaly
Gout
Arthritis
Treatment of polycythaemia vera
Phlebotomy to maintin haematocrit below 45%
Aspirin - anti-platelet
Cytoreduction
What are the types of secondary polycythaemia
Physiologically appropriate - increased EPO production is caused by recognisable problem
Physiologically inappropriate - increased EPO production not associated with pathology that would cause it to rise
What is thrombocytosis and what are its common causes
Increase in platelet count compared to normal range
Common causes:
Infection
Inflammation
Tissue injury
Haemorrhage
Cancer
Redistribution of platelets - post-splenectomy and hyposplenism
What is essential thrombocythaemia and how is it caused
Thrombocytosis caused by a myeloproliferative neoplasm where there is overproduction of platelets by megakaryocytes
Half of the cases are caused by JAK2 mutations
What are the common symptoms of essential thrombocythaemia
Numbness in extremities
Thrombosis
Disturbances in hearing and vision
Headaches
Erythromegelalgia (burning pain in hands/feet)
What is thrombocytopenia
Condition where there is an abnormally low level of platelets
How can platelet disorders be classified
Quantitative - low number
Qualitative - defective number, usually normal number
How can thrombocytopenia be classified
Inherited (rare)
Acquired
- Decreased platelet count
- Increased platelet consumption
- Increased platelet destruction
When do you get and what are the consequences of thrombocytopenia
Symptoms occur when platelet count >30
Easy bruising
Petechiae
Purpura
Mucosal bleeding
Severe bleeding after trauma
Intercranial haemorrhage
What is immune thrombocytopenic purpura (ITP)
Autoimmune disease characterised by isolated thrombocytopenia - can have acute or chronic course
Mainly due to atni-platelet auto-antibodies against glycoprotein
What are the causes of ITP
Acute infection
Associated autoimmune diseases - RA or systemic lupus erythematosus
Underlying lymphoid cancers
HIV
What is primary myelofibrosis
Myeloproliferative neoplasm where proliferation of mutated haematopoietic stem cells results in reactive bone marrow fibrosis leading to replacement of marrow with scar tissue. Usually caused by JAK2 mutation
Leaves little space for haemopoiesis so extramedullary haemopoiesis takes place
What is secondary myelofibrosis
Where myelofibrosis has developed as a consequence of polycythaemia vera or essential thrombocythaemia
What are the symptoms of primary/secondary myelofibrosis
Heaptomegaly
Splenomegaly
Fatigue
Weight loss
Fever
Increased sweating
Portal hypertension
What is the difference between chronic and acute leukaemias
Acute - rapidly cause bone marrow failure due to larger numbers of immature blast cells overwhelming ability of tissue to produce mature blood cells
Chronic - slow to cause symptoms and often have differentiation of the cells
What is chronic myeloid leukaemia
Unregulated growth of myeloid cells in the bone marrow leading to accumulation of mature granulocytes and myelocytes in the blood
Caused by philadelphia chromosomes (reciprocal translocation between chromosomes 9 and 22)
Translocation results in an oncoprotein (BCR-ABL) with tyrosine activity that causes proliferation, differentiation and inhibition of apoptosis
How is chronic myeloid leukaemia treated
Drug used which inhibits ATP-binding site on tyrosine kinase
What is pancytopenia and classify how it it caused
It is a reduction in white cells, red cells and platelets
Either caused by increased removal or decreased production
Pancytopenia - increased removal causes:
Immune-destruction
Splenic pooling
Haemophagocytosis
Pancytopenia - reduced production causes:
B12/folate deficiency
Bone marrow infiltrated by malignancy
Marrow fibrosis
Radiation
Drugs
Viruses
Idiopathic aplastic anaemia
Congenital bone marrow failure
What is aplastic anaemia
Where the bone marrow cannot produce mature blood cells, caused by damage to the bone marrow and haematopoietic stem cells leading to pancytopenia
What causes aplastic anaemia
Genetic causes
Auto immunity
Exposure to chemicals, drugs or radiation
