Week 2 - ITS Poblems - White cells, Pancytopenia, Polycythaemia rubra vera, Essential Thrombocythaemia

Question 1

Station 1 - White cells a) What crises would require increased production of white cells?

Answer 1

Any response to inflammation- bacterial, viral infection, malignancy etc

Question 2

b) What are the different functions of each type of white cell?

Answer 2

Neutrophils - bacterial infection - phagocytosis Lymphocytes - respond to viral infections as well as antibody production Monocytes - Phagocytose and APC Eosinophils - Allergic response and parasitic infections Basophils - hypersensitivity reactions (allergies/parasites)

Question 3

Our bone marrow has the potential to hugely increase the production of white cells as an appropriate response to many crises. This results in a reactive leucocytosis in the peripheral blood. c) What other kind of leucocytosis would you be concerned about?

Answer 3

Would be concerned about malignant causes of leucocytosis

Question 4

e) What is meant by the term clonality? What type of clonality would a reactive leucocytosis have?

Answer 4

This is the proliferation determined by the parent cell - daughter cells arising from multiple parents are polyclonal Reactive leucocytosis would have a polyclonal clonality When there are daughter cells that arise from one parent - monoconal

Question 5

Station 2 - This woman has major problems. For the last week she has been feeling tired and breathless and has been fighting an infection. Eventually she went to see the doctor because she had some unexplained bruising on her legs. She thought it was all down to iron deficiency anaemia which she had had before but when the Full Blood Count came back she had pancytopenia. a) What is meant by the term Pancytopenia ann why is it potentially serious?

Answer 5

This refers to anaemia, leucopenia and thrombocytopenia Can be serious as it leaves the patient open to bleeds as well as infection as well as anaemia symptoms

Question 6

In pancytopenia the bone marrow is, of course, not able to do its job properly. One basic mechanism causing bone marrow failure is aplastic anaemia in which there is hypoplasia of the haemopoietic tissue. What causes aplastic anemia?

Answer 6

Aplastic anaemia is caused by the autoimmune destruction of the HSC where auto-reactive T cells produce TNFa and IFNy which attack the HSC The bone marrow is hypocellular in this condition

Question 7

c) Suggest two other processes other than bone marrow hypoplasia which would also cause pancytopenia.

Answer 7

Inherited disorder Fanconi’s anaemia B12/folate deficiency Drugs and infiltration disorders Hypersplenism Myelofibrosis

Question 8

Station 3 - Too many reds a) What are the normal red cell parameters that are commonly measured in clinical practice?

Answer 8

This would be Hb (haemoglobin) RCC (red cell count) MCV (mean cell volume) Hct (haematocrit) MCH (mean cell haemoglobin) MCHC (mean cell haemaglobin concentration)

Question 9

Often people think that if you have a high haemoglobin you must have a true polycythaemia but this is not always the case. b) Do you know why?

Answer 9

There can be secondary polycthaemia where the Hb/Hct is increased because the body is exposed to chronic hypoxia (smoking, COPD) or there is an EPO secreting tumour or A psuedopolycthaemia where the patients plasma volume has been depleted ie deydrated or diuretic effect leading to an increased haemotcrit The person therefore does not have a polycythaemia in the absence of reactive changes

Question 10

In the case of a true polycythaemia the body is producing too many red blood cells. c) What would drive the marrow to produce too many red blood cells?

Answer 10

This could be due to a mutation in the JAK2 pathway which would cause the cells to lose their autoinhibition and therefore lead to unregulated proliferation of the blood cells

Question 11

d) How would myeloproliferative polycythaemia present clinically?

Answer 11

Facial plethora The blood would be very viscous and therefore could cause small vaso-oclusions leading to erythromelalgia (pain in hands and feet + redness), light headedness Patient would also have an enlarged spleen (splenomegaly) as well as potentially an enlarged liver Patient could also present with gout due to increased urate from red cell turnover Patients have the characteristic pain after a hot bath/shower

Question 12

e) Why should we be concerned if there are too many red blood cells? What is the treatment of polycythaemia rubra vera? (for low and high risk patients)

Answer 12

Should be concerned as this can make the blood very viscous leading to stasis of blood which can cause clots or simply slow the flow to vital organs Treatment Venesection to maintain Hct 60 or previous thombotic event

Question 13

What is given to treat an acute attack of gout?

Answer 13

NSAIDs are given to treat an acute attack - ibuprogen or diclofenac Second line would be colchicine (steroids are also an option)

Question 14

How long after the acute attack of gout is urate lowering drugs started? (Aim for urate levels <0.3mmol/l) What drugs are given and what type of drug are they known as?

Answer 14

These are started 2-3 weeks after the acute attack of gout Give the patient allopurinol (1st line) or febuxostat (2nd line) Allopurinol is a purine selective xanthine oxidase inhibitor Febuxostat is a non-purine selective xanthine oxidase inhibitor

Question 15

https://s3.amazonaws.com/classconnection/403/flashcards/11907403/png/picture2jpgpngjpgpngjpg-1623F97EDBF256CEBB0.png

Answer 15

The fact that the swelling is tender is a good sign against lymphoma or metastases - makes you think bacterial or viral * A) - high haemoglobin (polycythaemia), high platelets (thrombocytosis), high WCC (leucocytosis) * B) Thrombocytosis is a condition in which too many platelets are produced, thrombopenia is a condition in which there are not enough platelets * C) - Essential thrombocythaemia and reactive changes are when the bone marrow over produces platelets - reactive changes is more common

Question 16

What are the reactive changes causes of thrombocytosis?

Answer 16

Bleeding Infection Chronic inflammation Post-surgery Iron deficiency anaemia Even hypoxia also

Question 17

https://s3.amazonaws.com/classconnection/403/flashcards/11907403/png/picture2jpgpngjpg-1623F9C7927680D4929.png

Answer 17

D) Most recent FBC - potential essential thrombocythaemia E)Her toe has turned blue due to too many cells has caused increased viscous blood leading to a small vessel getting clocked up leading to necrosis , inflammatory markers would probably be normal F) - would want to give the patient anti-platelets or cytotoxic drugs if high risk

Question 18

What are the tests used in the diagnosis of essential thrombocythaemia?

Answer 18

Bone marrow aspirate/biopsy - would show hyperceullarity with an increased number of megakaryocytes Genetic tests - JAK2 mutation poisitve in 50% of patients If this is negative measure calreticulin (CALR) or MPL mutation This mutations account for 85% of patients in total

Question 19

What is the treatment for essential thrombocythaemia? (low and high risk)

Answer 19

If low risk then anti-platelets low dose (75mg aspirin daily) If high risk (>60 or previous thrombosis) - hydroxycarbamide If hydroxycarbamide wont work then agrnenulide or interferon alpha (Cytoreductive chemo (this suppresses bone marrow getting platlet count to normal range))