MPD Flashcards
Define what a myeloproliferative disorder is ?
- This is a group of disorders which cause bone marrow lineage(s)(granulocytes, red cells & platelets) to grow or multiply by rapidly producing new tissue, parts, cells, or offspring
- These are caused by clonal prolifertion of haematopoietic myeloid stem cells in the marrow, these stem cells retain the ability to mature and differentiate so result in the production of abnormal RBC’s, WBC’s or platelets
What is the difference between MPD and acute leukaemia ?
maturation is relatively preserved – so seeing lots of mature cells instead of lots of immature cells ‘blasts’
In MPD what type of cells can there be an increase of seen ?
RBC’s, Platelets or white blood cells
What are the 4 main types of MPD’s and what cell type is being rapidly proliferated in them?
- RBC proliferation caused by Polycythaemia rubra vera (PRV)
- WBC proliferation is caused by chronic myeloid leukaemia (CML)
- Platelet proliferation is caused by essential thrombocytopenia (ET)
- Fibroblast proliferation caused by myelofibrosis
When should you considered a MPD ?
- High Granulocyte count
- ±High Red cell count / haemoglobin
- ± High Platelet count
- ± Eosinophilia/basophilia
Basically if anyone of these is high and there is no reactive explanation for them being high
- Splenomegaly
- Thrombosis in an unusual place
Give an example of a reactive cause which may result in a high HB, RBC, Hct?
COPD
This is due to EPO stimulating due to the hypoxia caused by the COPD resulting in increased RBC production
An increase in what 2 cell types if more suggestive of a MPD rather than a reactive cause ?
Increase in basophils and esoinophils
What is chronic myeloid leukaemia ?
It is uncontrolled clonal proliferation of myeloid cells it most often causes an increase in WBC’s, recall it is a MPD so the abnormal cells being produced are morphologically distinguishable
- Granulocytes and their precursors
- Can affect other lineages (platelets) (so platelet count is variable)
But mainly it is the increase in WBC’s
What are the 3 phases of CML ?
Chronic phase - most people are diagnosed in this phase, it is the phase where the leukaemia is most stable and slow growing, people have few if any symptoms during this phase (hence CML is often asymptomatic)
Accelarated phase - In the accelerated phase, you have more obvious symptoms. You might notice that you feel more tired than usual. You may lose weight. Your tummy (abdomen) might be swollen due to an enlarged spleen. This might give you an uncomfortable or painful feeling to the left of your stomach, under your ribs.
The blast phase is also called the acute phase, blast crisis or blast transformation. This is when the leukaemia transforms into an acute leukaemia (usually acute myeloid leukaemia). In this phase many blast cells fill the bone marrow. There are also more blast cells in the blood. You can feel quite unwell and your symptoms could be troublesome. Your spleen is enlarged. Basically features of acute leukaemia +/- death
What are the clinical feature of CML ?
- Asymptomatic
- Splenomegaly - this can cause early satiety
- Hypermetabolic symptoms
- Gout
- Problems related to hyperleucocytosis problems, Priapism (prolonged erection of the penis often painful), visual disturbances (due to having that many cells in the blood which can cause sludging)
- Weight loss, tirdness, fever and sweats
- Can get hepatomegaly, anaemia, bruising (depends on related cell counts)
What are the typical blood count changes seen in CML ?
- Normal/↓Hb
- Leucocytosis (increased WBC) with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
- Thrombocytosis (can be variable)
What is the characteristic chromosomal mutation associated with CML ?
Philidelphia chromsome - t(9,22)
- A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22
- The new chromsome 22 is termed the philidelphia chromosome
What does the gene BCR-ABL 1 on the philidelphia chromsome do ?
The gene product is a tyrosine kinase which causes abnormal phosphorylation (signalling) leading to the haematological changes in CML by speeding up cell division and inhibiting DNA repair
What specific drug is given to treat CML with presence of philidelphia chromsome ?
Imatinib - it is atyrosine kinase inhibitor
What are the BCR-ABL 1 negative MPD ?
Simply the other 3 MPD’s:
- Polycythaemia rubra vera (PRV)
- Essential thrombocythaemia (ET)
- Idiopathic myelofibrosis (IMF)
Describe what a pseudopolycythaemia is and its causes are
- This is when a polycythaemia is registered but it is actually due to an decrease in plasma volume resulting in an increase in Hb
- Polycythaemia being an increase in Hb/Hct
The causes of pseudopolycythaemia include:
- Dehydration due to e.g. alcohol or diuretics
- Obesity also can cause it
