Haem Malignancy: Myloproliferative Disorders And Myelodysplastic Disorders Flashcards
What are myeloproliferative disorders?
Caused by clonal proliferation of haematopoietic myeloid stem cells in the bone marrow.
These cells can differentiate into RBCS, WBCS, or platelets, causing an excess of one or more of these cell types
What types of myeloproliferative disorders do you get?
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythaemia
Dr Tom says above are 3 main
Myeloproliferative disorders have the potential to progress and transform into ……?
What gene mutations are myeloproliferative disroders associated with?
- Can progress and transform into acute myeloid leukaemia
Gene mutations:
* JAK2
* MPL
* CALR
TOM TIP: Remember the JAK2 mutation for your exams. This can be the target of JAK2 inhibitors such as ruxolitinib.
What is polycythaemia vera?
what is it caused by?
- myeloproliferative disorder characterised by the excess production of erythrocytes.
- 98% of cases caused by a genetic mutation in the JAK2 gene
Myeloproliferative disorders result in the excess production of myeloid cells: erythrocytes (red blood cells), platelets or granulocytes (neutrophils, eosinophils and basophils).
When excess red blood cells are produced resulting in a raised haemoglobin concentration and haematocrit this is called…?
polycythaemia
Contrast primary and secondary polycythaemia
primary polycythaemia
* polycythameia vera - excess erythroyctes due to JAK 2 gene
Secondary polycythaemia
* physiological response to chronic hypoxia (i.e. smoking / chronic lung disease), renal e.g. renal artery stenoiss , or excess EPO (i.e. EPO secreting tumours)
RF for polycythemia vera ?
- Advancing age: median age at diagnosis is 60-70 years
- History of Budd-Chiari syndrome: a proportion of people will have a JAK2 mutation even if they had initially normal blood counts
RF for polycythemia vera ?
- Advancing age: median age at diagnosis is 60-70 years
- History of Budd-Chiari syndrome: a proportion of people will have a JAK2 mutation even if they had initially normal blood counts
History of symptoms fro Polycythaemia vera?
- Headaches: usually associated with dizziness and sweating
- Myalgia and weakness
- Fatigue
- Tinnitus
- Pruritis: particularly after a hot shower or bath
- Erythromelalgia: burning pain, warmth and redness in the hands and feet
- Blurred vision: temporary loss of vision due to hyper-viscosity
- Dyspepsia: peptic ulceration
- Gout: due to increased cell turnover
- thrombosis (75% arterial) i.e presnt with STROKE, MI, DVT, PE, BUDD CHIARI sydnrome
What might you see when clinically examinaing a pt with polycythaemia vera?
- a ‘ruddy’ (reddish) / plethoric complexion
- Splenomegaly
- Abdominal masses: benign and malignant uterine, renal and hepatic tumours which can secrete EPO may be palpable
- Hypertension
Differencial diagnosis for polycythaemia vera? i.e. raised HB
Hypoxia driven:
* COPD
* smoking
* carbon monoxide poisoning
* sleep apnoea
* left to right cardiac shunts (Eisenmenger’s syndrome)
* high altitude
Local renal hypoxia:
* e.g.renal artery stenosis
Pathological EPO production:
* EPO secreting tumours; e.g. clear cell renal carcinoma, Wilms’ tumour, hepatocellular carcinoma, cerebellar haemangioblastoma, pheochromocytoma, uterine myoma, parathyroid carcinoma and meningioma
Investigations for polycythaemia vera: how is it defined in terms of lab resutls
dont think really need to know off by heart
Polycythaemia is defined as:
- Haemoglobin (Hb) >185 g/L and/or haematocrit (Hct) > 0.52 in males
- Hb >165 g/L and/or Hct > 0.48 in females
- Red cell mass >25% above predicted
If a pt is dehydrated they may have apparent polycythaemia. The hb and haematocrit is riased.
why is it raised?
What can you look at to work if true polycythaemia?
What other lab results may be raised?
- Hb / Hct is raised due to reduced plasma volume (dehydrated)
- look at - red cell mass - will be normal
- Neutrophilia and thrombocytosis often see in PV
What are other lab investigations for Polycythaemia vera? think about ruling stuff in / out
FBC:
* high: RCC, Hb, HCt, PCV, WBC, platelets
Blood film:
* assess for leukaemia - require BM assessment
U&E/LFTs:
* renal/hepatic causes ( tumours), complications (e.g. Budd-Chiari syndrome)?
Serum ferritin:
* normal or low - big demand for iron
Arterial blood gas:
* hypoxia? (smoking) raised carboxyhaemoglobin?
Serum EPO:
* suppressed levels - PV.
* raised levels -secondary cause; inappropriate EPO production and the possibility of an EPO-secreting tumour.
JAK 2 V617F mutational analysis:
* positive in 95% of patients with PV
Specialist investigations and imaging for poylcythaemia vera?
Bone marrow biopsy:
* to distinguish from secondary PV
* hypercellularity, erythroid hyperplasia
Imaging:
* Abdominal US - splenomegaly and exlcude secondary causes of PV i.e. renal and hepatic
* CT head/neck/chest/abdo/pelvis - rare EPO secreting tumours
How are pts with Polycythaemia managed?
Phlebotomy
* intemrittend and long term to keep haematocrit <0.45
Aspirin
* reduce thrombotic events and death
Cytoreductvie therapy
* hydroxycaramide - first line
* interferon-alfa - child bearing women as not teratogenic
complications ofr Polycythaemia vera?
Ischaemic stroke
Myocardial infarction
Pulmonary embolism
Progression to myelofibrosis or acute myeloid leukaemia
Gastrointestinal haemorrhage
Budd-Chiari syndrome
What is myelofibrosis?
what can it result in?
- proliferation of the cell line leads to fibrosis of the bone marrow.
- This is due to cytokines e.g. fibroblast growth factor released by cells.
- leading to anaemia and leukopenia
- the BM is full of scar tissue and so extramedullary haematopoiesis happens elsewehere e.g. liver and spleen.
- leading to hepatomegaly and splenomegaly.
- resulting in- portal HTN.
- If it occurs around the spine- spinal cord compression.
What is myelofibrosis caused by?
- primary myelofibrosis
- polycythaemia vera
- essential thrombocythaemia.
How might a patient with myelofibrosis present?
- night sweats
- fever
- weight loss
- abdominal discomfort (splenomegaly)
- low Hb (BM failure)
- infections (BM failure)
- bleeding (BM failure)
Investigations and results for myelofibrosis?
include the diagnostic test
FBC
* anaemia low Hb
* Leukocytosis OR leukopenia
* Thrombocytosis or Thrombocytopenia
Blood film
* Leukoerythroblastic cells, characteristic teardrop RBCS, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).
Bone marrow trephine for diagnosis
* may be ‘dry’ as scar tissue
Genetic testing:
* JAK2, MPL and CALR genes can help guide management.
How do you manage primary Myelofibrosis?
patient with mild disease and minimal symptoms:
* Watch and wait
Allogenic stem cell transplant
* can be curative but has risks
Chemotherapy
* contol disease, improve symptoms, slow progession
* not curative on its own
Supportive
* anameia, splenomegaly, portal HTN
What is essential thrombocythaemia?
What can it cause?
A clonal proliferation of megakaryocytes leads to persistently high platelets, > 600 x 109/l) with abnormal function.
Can cause:
* bleeding
* arterial / venous thrombosis
* microvascular occlusions - headache
* atypical chest pain
* light headesness
* erythromelalgia
some sources say platelets > 1000 x 109
What are some causes of thrombocytosis?
This is result of BM biospsy- marrow trephine in myelofibrosis:
What are other causes of marrow fibrosis?
- any myeloproliferative disorder
- lymphoma
- secondary carcinoma
- TB
- leukaemia
- irradiation
For interest slide - see images
Treatment of essential thrombocythaemia?
- aspirin 75 mg OD
- hydroxycarbamide in high risk patients
What signs and symptoms of underlying conditions might you see in any pts with myeloproliferative disorders ?
dr tom
- Anaemia (except in polycythaemia)
- Splenomegaly (abdominal pain)
- Portal hypertension (ascites, varices and abdominal pain)
- Low platelets (bleeding and petechiae)
- Thrombosis is common in polycythaemia and thrombocythaemia
- Raised red blood cells (thrombosis and red face)
- Low white blood cells (infections)
What is Myelodysplastic syndrome? what blood results may you see?
- myeloid bone marrow cells do not mature properly
- bone marrow failure
- Many specific types of myelodysplastic syndrome.
- low levels of blood components that originate from the myeloid cell line:
- Anaemia
- Neutropenia (low neutrophil count)
- Thrombocytopenia (low platelets)
Who gets Myelodysplastic syndrome?
- patients > 60 years
- patients who have previously had chemotherapy or radiotherapy.
What is the risk of Myelodysplastic syndrome?
increased risk of transforming into acute myeloid leukaemia.
How might a patient with myelodysplastic syndrome present?
- asymptomatic - incidental FBC finding
- anameic - fatigue, pallor, SOB
- neutropenia - infections ( can be lifethreatening)
- thrombocytpenia - purpura / bleeding
Investigations for Myelodysplastic syndromes ?
how is diagnosis confirmed?
FBC
* pancytopenia
* macrocytic anaemia
* low reticulocyte count
Blood film:
* blasts present
Diagnosed with BM biopsy
* marrow cellularity due to ineffective haematopoiesis
Treatment for myelodysplastic syndromes
Watch + wait
Transfusions
* red cells / platelets
* EPO
Allogenic stem cell transplant
* curative but risky
Chemotherapy -QOL if symptomatic
