Haemopoeisis gone wrong

Question 1

how might this happen?

Answer 1

• overproduction : myeloproliferative disorders, neoplasms.

- underproduction : aplastic anaemia, platelets and thrombocytopenia.

Question 2

what myeloproliferative disorders affect haemopoiesis?

Answer 2

• essential thrombocythaemia.
• polycythaemia vera.
• myelofibrosis.
• chronic myeloid leukemia.
• disregulation at multipotent haemotopoietic stem cell.

Question 3

what clinical features are seen in myeloproliferative disorders?

Answer 3

• overproduction of one or several blood elements with dominance of transformed clone.
• marrow fibrosis.
• cytogenetic abnormalities.
• extramedullary haemopoeisis.
• transformation to acute leukaemia.

Question 4

whats the link between gene mutation and myeloproliferative disorders?

Answer 4

• mutation in JAK2 gene a cytoplasmic tyrosine kinase causes increased proliferation and survival of haemotopoietic precursors.

Question 5

what is polycythaemia vera?

Answer 5

• 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.

Question 6

what are the clinical features of polycythaemia vera?

Answer 6

• significant cause of arterial thrombosis.
• venous thrombosis.
• haemorrhage into skin or GI.
• pruritis.
• splenomegaly.
• gout.

Question 7

how is polycythaemia managed?

Answer 7

• venesenction to maintain haemocrit.
• aspirin unless contraindicated.
• manage CVS risk factors.
• drugs to reduce overproduction of cells.

Question 8

why else would there be an excess of red cells? and why?

Answer 8

• 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.

Question 9

what could cause secondary polycythaemia?

Answer 9

• 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.

Question 10

what causes essential thrombocythaemia?

Answer 10

• excess platelets in blood. due to large and excess megakaryocytes in bone marrow.

Question 11

how is essential thrombocythaemia managed?

Answer 11

• 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.

Question 12

what are the other causes for a high platelet count that you must eliminate before diagnosing ET as persistent and not transient?

Answer 12

• infection.
• inflammation.
• other tissue injury like RH arthritis.
• haemorrhage.
• cancer.
• redistribution of platelets like in hyposplenism.

Question 13

what is myelofibrosis?

Answer 13

• 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.

Question 14

what are the clinical features of myelofibrosis?

Answer 14

• severe constitutional symptoms like fatigue, sweats.
• massive splenomegaly.
• progressive marrow failure requiring transfusions.
• transforms to leukaemia.

Question 15

what is CML?

Answer 15

• 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.

Question 16

what chromosomal feature is seen in CML?

how had this helped develop treatment?

Answer 16

• 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.

Question 17

what is pancytopenia? why is this caused?

Answer 17

• 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.

Question 18

what could cause pancytopenis due to reduced production?

Answer 18

• B12/ folate deficiency.
• BM infiltration.
• marrow fibrosis.
• radiation.
• drugs : chemo.
• viruses.
• idiopathic aplastic anaemia.
• congenital BM failure.

Question 19

what is aplastic anaemia?

Answer 19

• pancytopenia with hypocellular BM in absence of abnormal infiltrate with no increase in reticulin.

Question 20

what are platelets and their functions?

Answer 20

• adhesion to damaged endothelium.
• activation and release of granules.
• aggregation forming platelet plugs.

Question 21

platelets disorders can be quantitative or qualitative. how?

Answer 21

• quantitative : low/ thrombocytopenia.

- qualitative : normal number but defective function.

Question 22

what are some acquired reasons for thrombocytopenia?

Answer 22

• decreased platelet production : B12/ Folate deficiencies, leukemias, liver failure, sepsis.
• increased consumption : haemorrhage etc.
• increased destruction : autoimmune, hypersplenism, splenic pooling.

Question 23

what are some consequences of severe thrombocytopenia?

Answer 23

• count under 30.
• easy bruising.
• petechiae, purpura.
• mucosal bleeding.
• severe bleeding in trauma.
• intracranial haemorrhage/

Question 24

what is immune destruction?

Answer 24

• caused by immune thrombocytopenic purpura.
• secondary to autoimmune diseases possible like CLL.
• treated with immunosuppression corticosteroid.
• platelet transfusion do not work as get destroyed!

Question 25

what are some disorders of platelet function?

Answer 25

• hereditary.

- acquired via aspirin/ NSAIDS/ clopidogrel, uraemia, myeloma, myeloproliferative disorders.