10- When Haemopoiesis Goes Wrong

Question 1

• what disorders does an overproduction of cells lead to, what about underproduction?
• give 4 diseases caused by an overproduction of cells. what are clinical features of an overproduction of cells?
• what is thought to be the cause of myeloproliferative disorders?

Answer 1

• overproduction=myeloproliferative disorders/neoplasms *yd’s regulation of multi potent haematopoeitic stem cell
• underproduction=aplastic anaemias, thrombocytopenia (platelets)
• essential thrombocythaemia, polycythaemia Vera, myelofibrosis, chronic myeloid leukaemia.
• hyper cellular bone marrow (full)/marrow fibrosis, other genetic abnormalities, extramedullary haemopoeisis (liver/spleen/sk bone)
• many patients have a specific point mutation in 1 copy of the JAK2 gene

Question 2

• what type of cell is overproduced in polycythaemia vera? what is typical patient profile w this disease?
• what are the clinical features ie what can it cause in the body?
• how is this condition managed?

Answer 2

• RBCs therefore would have an abnormally large haematocrit or raised red cell mass
• typically affects males and females equally, median age=60 yrs, no reactive cause
• as there’s a much larger blood volume it often causes arterial thrombosis, sometimes venous thrombosis, haemorrhage into skin or GI, pruitis (itching), gout, splenomegaly.
• venesection to remove blood and maintain the haemocrit at a normal level, aspirin or other anticoagulants, managing CVS risks.

Question 3

• define polycythaemia, what types are there?
• explain the difference between primary and secondary polycythaemia
• give some causes of secondary polycythaemia.

Answer 3

• polycythaemia=an increase in the circulating red cell concentration typified by an increased haematocrit.
• increase can be:relative (normal haematocrit but plasma has been reduced eg dehydration making haematocrit look increased) or absolute (an increase in the red cell mass)
• primary=polycythaemia vera
• secondary=driven by EPO production, can be physiologically appropriate (eg in reponse to tissue hypoxia) or inappropriate.
• physiological response to central hypoxia= caused by chronic lung disease, R-> L shunts, training at altitude, CO poisoning (leading to increased EPO secretion), renal hypoxia bc of renal artery stenosis or polycystic disease. Abnormal EPO production= Hepatocellular carcinoma, renal cell cancer= both produce excess EPO.

Question 4

• define essential thrombocythaemia, what would you see on a blood film?
• give management steps.
• when a high platelet count has been noted, you must rule out reactive causes; give some.

Answer 4

• excess platelets in the blood, find large and excess megakaryocytes in BM (the large precursors), thrombotic events eg excess clotting in limbs causes gangrene due to tissue hypoxia then necrosis.
• any CVS risks eg thrombosis should be managed carefully, aspirin or other anti coagulants
• infection, inflammation (eg IBS, rheumatoid arthritis), other tissue injury eg surgery, burns, haemorrhage, cancer, post splenectomy (platelets are being redistributed)

Question 5

• define myelofibrosis, what can it also cause?
• give clinical features.
• what is chronic myeloid leukaemia? Give features.

Answer 5

• fibrosis of the BM: little space for haemopoeisis. can also cause massive splenomegaly and hepatomegaly due to extramedullary haematopoiesis.
• may be end result of PV or ET or primary disease (pmf-which starts w proliferation phase when all counts may be high)
• advanced disease=severe constitutional symptoms eg fatigue, sweats. Massive splenomegaly leading to pain, rupture.
• presents w very high WCC, symptomatic splenomegaly, hyperviscosity, mainly in adults.

Question 6

• define pancytopenia
• give reasons why it may occur (reduced production vs increased removal).
• what is aplastic anaemia? Prognosis?
• give reasons for how acquired thrombocytopenia may arise. Give clinical signs.

Answer 6

• a reduction of white cells, red cells and platelets (pan=ALL).
• reduced production= B12/folate deficiency, BM infiltration, marrow fibrosis.
• increased removal=immune destruction, splenic pooling.
• aplastic anaemia=pancytopenia w a hypocellular bone marrow in the absence of an abnormal infiltrate and w no fibrosis. Mortality HIGH.
• acquired= decreased production (B12/folate deficiency, liver failure therefore less EPO secreted), increased consumption (massive bleed, DIC), increased destruction (autoimmune). Clinical=easy bruising, purpura, mucosal bleeding,