When Haemopoiesis Goes Wrong Flashcards
What does overproduction of blood cells cause?
Myeloproliferative disorders/neoplasms
What does underproduction of blood cells cause?
Aplastic anaemia - all cells
Thrombocytopenia - platelets
Causes of overproduction of cells
Damage to bone marrow
Abnormal hormone signalling
Outline myeoproliferativee neoplasms
Overproduction due to disease in bone marrow
Often caused by genetic mutations in JAK2 gene
Types of myeloproliferative disorders
polycynthaemia vera
essential thrombocythaemia
primary myelofibrosis
chronic myeloid leukaemia
Outline polycythaemia
Excess erthyrocytes
Diagnosed by high haematocrit 52% men 48% women
Causes of polycythaemia
Relative - decreased plasma volume
Absolute - increased erythrocyte count
Outline absolute polycythaemia
Increase in number of erythrocyte
primary - abnormality in bone marrow
- e.g polycythaemia vera ONLY
secondary - increased EPO
- response to hypoxia
Outline polycythaemia Vera
Absolute primary polycythaemia
A myleoproliferative neoplasm
Mutation of JAK2
Excess erythrocytes due to abnormality in bone marrow
What does a mutation in JAK2 gene do?
Makes blood cell sin bone marrow hypersensitive to EPO
Causes proliferation of RBCs
Clinical features of polycynthaemia Vera
Thrombosis
Haemorrhage
Dizziness
Pruritis
Gout
Splenomegaly
Management of polycythaemia Vera
Venesection to maintain haematoocrit to <45%
Aspirin 75mg
Manage CVS risk factors
What is thrombocytosis?
Increased platelet count
Outline essential thrombocythaemia
- A myleoproliferative neoplasm
- Over production of megakaryocytes > excess platelets in blood
- Mutation in JAK2 gene or thrombopoietin receptor
Symptoms of essential thrombocythaemia
Numbness in extremities
Thrombosis
Headaches
Issues with vision + hearing
Treatment of essential thrombocythaemia
Low risk for bleeding - aspirin
High risk for bleeding - hydroxycarbamide
Types of thrombocytosis
- primary - essential thrombocythaemia
- secondary - normal bone marrow response to extrinsic factors e.g. infection
- redistributional: platelets redistributed from splenic pool into blood
Outline primary myleofibrosis
Proliferation of mutated haemopoietic stem cells
Results in reactive bone marrow fibrosis
Leads to collagen deposition >pancytopenia + schistocytes + tear drop cells
Mutation in JAK2 gene (+ CALR and MPL gene)
What is pancytopenia?
Decrease in levels of all blood cells
Symptoms of primary myelofibrosis
Hepatosplenomegaly
Bruising
Fatigue
Weight loss
Fever + sweating
Portal hypertension
Types of leukaemia
Acute or chronic
Myeloid - from myeloid lineage > RBCs, platelets, monocytes, granulocytes
Lymphoid - from lymphoid lineage > lymphocytes, B+ T cells
Outline chronic myeloid leukaemia
- Unregulated growth of myeloid cells in bone marrow > accumulation of granulocytes - many white cells
- mutation on chromosome 9 and 22 via reciprocal translocation - Philadelphia chromosome
- switches on a receptor tyrosine kinase > proliferation
Symptoms of chronic myeloid leukaemia
Splenomegaly
Sticky blood
Bone pain
Outline aplastic anaemia
- inability of stem cells to generate mature blood cells
- results in bone marrow + haemopoetic stem cell damage
- leads to pancytopenia
Causes of aplastic anaemia
Genetic
Autoimmune
Exposure to chemical, medication + dugs
Treatment of aplastic anaemia
Immunosuppressants
Bone marrow transplant - risk of new WBCs attacking body
Causes of pancytopenia
Splenic pooling
Haemophagocytosis
Immune destruction
B12/folate deficiency
Infection
Drugs
Idiopathic aplastic anaemia
Primary myelofibrosis
What is thrombocytopenia?
- low platelet count
Outline acquired thrombocytopenia causes
decreased platelet production:
- B12/folate deficiency - cant make megakaryocytes
- liver failure - less thrombopoetin
increased platelet consumption
- massive haemorrhage
- DIC
- thrombic thrombocytopenia purpura
increased platelet destruction:
- Hypersplenism - splenic pooling + more destruction
- drug induced
- autoimmune thrombocytopenia
What are the three causes of acquire thrombocytopenia?
- decreased platelet production
- increased platelet consumption
- increased platelet destruction
Symptoms of thrombocytopenia
Bleeding in gums
Nosebleeds
Petechiae
Outline thrombotic thrombocytopenia purpura
- Increased blood clotting in small vessels > decreased platelets
- caused by platelet activation due to endothelial damage
- may schistocytes
Outline immune thrombocytopenia purpura
Autoimmune disease
Immune platelet destruction
Caused by anti-platelet autoantibodies
Treatment of immune thrombocytopenia purpura
Immunosuppression
NOT platelet transfusion - will get destroyed
What drug is used to treat chronic myeloid leukaemia?
Imatinib
Tyrosine kinase inhibitor
(TK normally drives white cell proliferation)
Name the triad of conditions in Felty’s syndrome
RA
Neutropenia
Splenomegaly
