Myeloproliferative Disease Flashcards
What is meant by a myeloproliferative disease?
- “myelo” = type of cell lineage
- “proliferative” = grow/multiply rapidly
How are myeloproliferative diseases different from acute leukaemias which also have a proliferation of blast cells?
Acute leukaemia = blast cells can’t mature
MPD = increased no. of blasts which can mature
How are myeloproliferative diseases classified?
- Either BCR-ABL1 negative or positive
Negative:
- Myelofibrosis
- Polycythaemia Vera (PV) (increased RBCs)
- Essential Thrombocythaemia (increased platelets)
Positive:
- Chronic Myeloid Leukaemia (increased granulocytes)
What blood count results would make you consider a myeloproliferative disorder?
increased granulocyte count increased RBCs/Hb increased platelets Eosinophilia/Basophilia Splenomegaly Thrombosis in unusual place
Chronic Myeloid Leukaemia can cause an increase in platelets and RBCs as well as granulocytes. TRUE/FALSE?
TRUE
What are the clinical features of CML?
- can be asymptomatic
- splenomegaly
- hypermetabolic syndrome (early satiety and weight loss)
- Gout (due to increased DNA breakdown)
What lab findings are common in CML?
- Normal or low Hb
- neutrophilia
- Increased myeloid precursors
- eosinophilia/basophilia
- increased platelets
How can you differentiate chronic myeloid leukaemia from reactive change?
- reactive changes e.g. infection
- causes all WBCs to increase not just granulocytes
What genetic abnormality is present in Chronic Myeloid Leukaemia?
Translocation between chromosome 9:22
“Philadelphia Chromosome”
What does Polycythaemia Vera cause?
- increase in RBC production
=> increase in Hb, Hct and red cell mass
What can cause SECONDARY polycythaemia?
- chronic hypoxia
- smoking
- erythropoietin secreting tumour (or EPO doping)
What can cause PSEUDO polycythaemia?
plasma volume diminished so Hb and red cells look higher than they are
- dehydration
- diuretics
- obesity
What symptoms other than those common to Myeloproliferative disorders are present in PV?
- headache
- fatigue
- increased blood viscosity
- itch
What is usually identified on abdominal examination in patients with PV?
Splenomegaly
What mutation is present in 90% of patients with PV?
JAK2 mutation
What investigations are used to look for causes of SECONDARY and PSEUDO polycythaemia?
- CXR
- O2 sats
- arterial blood gas
- Drug Hx (check for diuretics/dehydration)
How is PV treated?
- venesection to correct haematocrit <0.45
- aspirin (to lower platelets)
- cytotoxic oral chemo (e.g. hydroxycarbamide)
What is essential thrombocythaemia?
- uncontrolled proliferation of platelets
- abnormal platelet function
- risk of thrombosis
- acquired von willebrands disease can occur and cause bleeding in late stage
What are the main clinical features of Essential Thrombocythaemia?
- vasoocclusive
- bleeding if patient acquires von willebrand disease
How can essential thrombocythaemia be diagnosed on blood film?
Isolated rise in platelets
What reactive causes may cause a rise in platelets similar to essential thombocythaemia?
blood loss (e.g. due to surgery)
inflammation
malignancy
iron deficiency
other blood results would be abnormal in these cases though
What genetic mutations are often present in essential thrombocythaemia?
JAK2
CALR
MPL
(but some patient’s will be triple negative)
HOw is essential thrombocythaemia treated?
- antiplatelets => aspirin
- cytoreductive therapy (controls proliferation)
- e.g. hydroxycarbamide, interferon alpha
When can myelofibrosis occur?
- idiopathic
- post-polycythaemia
What features occur in idiopathic myelofibrosis?
marrow fails and becomes dry/ fibrosed
=> extramedullary haematopoiesis takes over
What symptoms do patients with myelofibrosis experience?
- anaemia
- bleeding
- infection (as cant make granulocytes to fight it)
- splenomegaly (due to extramedullary haematopoiesis)
What can be seen on a blood film in Myelofibrosis?
- tear drop shaped RBCs (Poikilocytes)
- leucoerythroblastic change (nucleated red cells and other early myeloid cells in film)
Why is a trephine biopsy required in myelofibrosis?
- bone marrow aspiration will be dry due to fibrosis
What cells are not found on a bone marrow biopsy if a patient has myelofibrosis?
- fat cells
- these are usually common in marrow biopsy
How is myelofibrosis treated?
supportive treatments - transfusion, platelets, antibiotics
allogenic stem cell transplant
splenectomy
JAK2 inhibitors
What reactive causes can increase granulocyte count?
Infection
physiological (i.e. post surgery/steroids)
What reactive causes can increase the platelet count?
- infection
- iron deficiency
- malignancy
- blood loss
What reactive causes can increase the RBC count?
- dehydration (pseudo due to low plasma)
- hypoxia (secondary)
