Haemopoeisis gone wrong Flashcards
how might this happen?
- overproduction : myeloproliferative disorders, neoplasms.
- underproduction : aplastic anaemia, platelets and thrombocytopenia.
what myeloproliferative disorders affect haemopoiesis?
- essential thrombocythaemia.
- polycythaemia vera.
- myelofibrosis.
- chronic myeloid leukemia.
- disregulation at multipotent haemotopoietic stem cell.
what clinical features are seen in myeloproliferative disorders?
- overproduction of one or several blood elements with dominance of transformed clone.
- marrow fibrosis.
- cytogenetic abnormalities.
- extramedullary haemopoeisis.
- transformation to acute leukaemia.
whats the link between gene mutation and myeloproliferative disorders?
- mutation in JAK2 gene a cytoplasmic tyrosine kinase causes increased proliferation and survival of haemotopoietic precursors.
what is polycythaemia vera?
- originates in bone marrow.
- high haematocrit or raised red cell mass with predisposing JAK2 mutation in 95% patients.
- may also have high platelets and neutrophils.
what are the clinical features of polycythaemia vera?
- significant cause of arterial thrombosis.
- venous thrombosis.
- haemorrhage into skin or GI.
- pruritis.
- splenomegaly.
- gout.
how is polycythaemia managed?
- venesenction to maintain haemocrit.
- aspirin unless contraindicated.
- manage CVS risk factors.
- drugs to reduce overproduction of cells.
why else would there be an excess of red cells? and why?
- polycythaemia/ erythrocytosis.
- which is an increase in circulating RBC conc. seen as raised haematocrit.
- can be relative to low plasma vol. or absolute increase.
- primary to polycythaemia vera or secondary to EPO production.
what could cause secondary polycythaemia?
- physiologically appropriate EPO.
- pathological EPO production.
- central hypoxia : RL shunts, CO poisoning, Chronic lung disease.
- renal hypoxia : renal artery stenosis, polycystic disease.
- hepatocellular carcinoma, renal cell cancer etc.
what causes essential thrombocythaemia?
- excess platelets in blood. due to large and excess megakaryocytes in bone marrow.
how is essential thrombocythaemia managed?
- cardiovascular risk factors should be aggressively managed.
- aspirin as anticoagulant.
- high risk patients of over 60, platelet over 1500, disease related thrombosis/haemorrhage.
- return platelet count back to normal with drugs like hydroxycarbomide.
what are the other causes for a high platelet count that you must eliminate before diagnosing ET as persistent and not transient?
- infection.
- inflammation.
- other tissue injury like RH arthritis.
- haemorrhage.
- cancer.
- redistribution of platelets like in hyposplenism.
what is myelofibrosis?
- BM replaced with fibrous scar tissue which is the cause of massive splenomegaly, hepatomegaly, due to extramedullary haematopoiesis.
- clonal haemopoietic stem cell proliferates, starts with proliferative phase so many counts maybe high.
- end result of PV or ET or de novo.
- progressive pancytopenia due to bone marrow fibrosis and hypersplenism.
what are the clinical features of myelofibrosis?
- severe constitutional symptoms like fatigue, sweats.
- massive splenomegaly.
- progressive marrow failure requiring transfusions.
- transforms to leukaemia.
what is CML?
- chronic myeloid leukaemia which presents with very high WCC.
- symptomatic splenomegaly, hyperviscosity, or bone pain.
- blood film and marrow will show excess of all myeloids from blast through to fully mature neutrophils.
what chromosomal feature is seen in CML?
how had this helped develop treatment?
- philadelphia chromosome which is a rearrangement of chromosomes to mix 9 and 22 which results in a switching on of tyrosine kinase which drives proliferation.
- imatinib has been developed which competitively inhibits kinase so tumour cannot proliferate which is now used to treat which increased survival from 5-20 years compared to BM transplant.
what is pancytopenia? why is this caused?
- reduction in white cells, red cells and platelets.
- reduced production.
- increased removal due to immune destruction, splenic pooling (hypersplenism), haemophagocytosis where cells in BM chewing up cells.
what could cause pancytopenis due to reduced production?
- B12/ folate deficiency.
- BM infiltration.
- marrow fibrosis.
- radiation.
- drugs : chemo.
- viruses.
- idiopathic aplastic anaemia.
- congenital BM failure.
what is aplastic anaemia?
- pancytopenia with hypocellular BM in absence of abnormal infiltrate with no increase in reticulin.
what are platelets and their functions?
- adhesion to damaged endothelium.
- activation and release of granules.
- aggregation forming platelet plugs.
platelets disorders can be quantitative or qualitative. how?
- quantitative : low/ thrombocytopenia.
- qualitative : normal number but defective function.
what are some acquired reasons for thrombocytopenia?
- decreased platelet production : B12/ Folate deficiencies, leukemias, liver failure, sepsis.
- increased consumption : haemorrhage etc.
- increased destruction : autoimmune, hypersplenism, splenic pooling.
what are some consequences of severe thrombocytopenia?
- count under 30.
- easy bruising.
- petechiae, purpura.
- mucosal bleeding.
- severe bleeding in trauma.
- intracranial haemorrhage/
what is immune destruction?
- caused by immune thrombocytopenic purpura.
- secondary to autoimmune diseases possible like CLL.
- treated with immunosuppression corticosteroid.
- platelet transfusion do not work as get destroyed!
what are some disorders of platelet function?
- hereditary.
- acquired via aspirin/ NSAIDS/ clopidogrel, uraemia, myeloma, myeloproliferative disorders.
