Haemopoiesis gone wrong Flashcards
What are myeloproliferative disorders?
- group of disease of bone marrow where excess cells are produced
- genetic mutations affecting precursors of myeloid lineage = dysregulation at multipotent haematopoietic stem cell
What are the 4 types of myeloproliferative disorders?
1) Polycythaemia Vera
2) Essential thrombocythaemia
3) Primary myelofibrosis
4) Chronic myeloid leukaemia
What are some clinical features of Myeloproliferative disorders?
- overproduction of 1 or more blood elements
- hypercellular marrow/marrow fibrosis
- thrombic and/or haemarrhagic diatheses
- extra-medullary haemopoiesis
- potential to transform to acute leukemia
What is polycythaemia?
increase in circulating red cell concentration with a persistently raised haematocrit
-can be:
+relative = normal red cell mass with decreased plasma volume
+absolute = increased red cell mass
What is polycythaemia vera?
A primary absolute polycythaemia
What are some features of polycythaemia vera?
- venous thrombosis
- haemorrhage into skin or GI
- pruritus
- splenic discomfort
- gout
How is polycythaemia vera managed?
1) Venesection to maintain Hct < 0.45
2) Aspirin = anti-platelet effect to avoid arterial thrombosis
3) Cytoreduction agents
What are the causes of secondary (absolute) polycythaemia?
divided into physiologically appropriate, inappropriate and others
Appropriate = living at high altitudes, COPD Inappropriate = heptocellular carcinoma, renal cancer, uterine tumours Other = performance sports
What is essential thrombocythaemia?
overproduction of platelets by megakaryocytes in the BM
List common symptoms of essential thrombocythaemia
- numbness
- disturbance in hearing and vision
- headaches
- burning pain in hands or feet
- thrombosis
How is essential thrombocythaemia managed?
- Aspirin
- hydroxycarbomide = returns platelet count
- Cardiovascular risk factors should be aggressively managed
What is myelofibrosis?
Proliferation of mutated haemopoietic stem cells resulting in reactive bone marrow fibrosis = replaces marrow with scar tissue
What are the clinical features of myelofibrosis?
- Bruising
- Fatigue
- Weight loss
- Fever
- Sweating
- Hepatosplenomegaly
How is myelofibrosis managed?
-Hydroxycarbamide
-Folic acid
Blood transfussion
-Ruxolitinib = JAK2 inhibitor
What is chronic myeloid leukemia?
Unregulated growth of myeloid cells in BM = accumulation of mature granulocytes (mainly neutrophils)
How does chronic myeloid leukaemia present?
- Symptomatic splenomegaly
- Hyperviscosity
- Bone pain
- Associated with philadelphia chromosome (via reciprocal translocation)
What are the three ‘underproduction’ disorders?
1) Pancytopenia
2) Aplastic anaemia
3) Thrombocytopenia
What is Panyctopenia?
Reduction white cells, red cells and platelets
What are the causes of pancytopenia?
- B12/folate deficiency
- BM infiltration by malignancy
- Marrow fibrosis
- Radiation
- Drugs
- Increased removal (immune destruction, splenic pooling, haemophagocytosis = chewing up of cells in BM)
What is aplastic anaemia?
Pancytopenia with a hypocellular BM in absence of an abnormal infiltrate
What is thrombocytopenia?
abnormally low levels of platelets
What are the consequences of thrombocytopenia?
- Easy bruising
- Petechiae/purpura
- Mucosal bleeding
- Severe bleeding
How is thrombocytopenia acquired?
- Decreased platelet production (B12/Folate deficiency, liver failure, sepsis)
- Increased platelet consumption (massive haemorrhage, DIC)
- Increased platelet destruction (autoimmune thrombocytopenia purpura, drug induced e.g. heparin)
What is immune thrombocytopenia purpura and how is it treated?
- Common cause of thrombocytopenia
- Autoantibodies against glycoprotein IIb/IIa + GPlb/IX
- Treated with immunosuppressants or intravenous immunoglobulin
