Chronic Myeloproliferative Disorders Flashcards
What is meant by a myeloproliferative disorder?
Clonal haemopoietic stem cell disorders with an increased production of on or more types of haemopoietic cells. Maturation is relatively preserved, unlike acute leukemia
What are the two subtypes of myeloproliferative disorders?
- BCR - ABL1 Positive (Chronic Myeloid Leukemia)
2. BCR ABL1 Negative
What chromosome is mutated in CML?
Philadelphia chromosome
What is the problem in the philadelphia chromosome?
Balanced translocation from chromosome 9 to chromosome 22
What are the three stages on CML?
Chronic
Accelerated
Blast crisis
What clinical features are you looking for in CML?
Splenomegaly
Hypermetabolic syndrome
Gout
What will the blood count look like in CML?
Normal/low Hb
Leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
What does the philidelphia chromosome cause?
A new gene - BCR - ABL 1
What is the gene product of the philidelphia chromosome and what does it do?
Tyrosine kinase which causes abnormal signalling and the haematological changes seen in CML
What is the treatment for CML and how does it work?
Tyrosine kinase inhibitor (Imatinib)
What are the three BRC - AB41 negative myeloproliferative disorders?
Polycythaemia rubra vera
Essential thrombocythaemia
Idiopathic myelofibrosis
What are the causes of secondary polycythaemia?
Chronic hypoxia (eg in COPD)
Smoking
EPO secreting tumout
What is a cause of pseudopolycythaemia?
Dehydration (Decreased plasma volume with result in disproportionate red cell numbers)
A patient presents with headaches, fatigue and says they get very itchy after every bath or shower.
Polycythaemia Rubra Vera
What is the most important test to do to confirm a diagnosis of Polycythemia Rubra Vera?
JAK2 mutation status
What is the genetic mutation see in almost all patients with Polycythemia Rubra Vera?
JAK2
What % of patients with Polycythemia Rubra Vera have the JAK2 gene?
95%
What is JAK2 and what does it do?
A kinase that results causes a loss of auto inhibitions
List all the main investigations you would do for Polycythemia Rubra Vera
FBC Blood film JAK2 status CXR 02 sats
What is the treatment of Polycythemia Rubra Vera?
Venesection
Aspirin
Cytotoxic oral chemotherapy (Hydroxycarbamide)
What is essential thrombocythaemia?
Uncontrolled production of abnormal platelets
What symptoms do patients get in essential thrombocythaemia?
Thrombosis Bleeding (due to acquired von willebrend disease) Microvascular Occlusion Gout Fatigue
How do you diagnose essential thrombocythaemia?
Exclude reactive cause (blood loss, inflammation, malignancy, iron deficiency)
JAK2 mutation
What is the treatment for essential thrombocythaemia?
Treatment dependent on age (younger patients most likely don’t need any treatment) but older patients need anti thrombotic agents such as aspirin.
Cytoreductive therapy to control proliferation (hydroxycarbamide)
What is myelofibrosis?
A condition in which an abnormal clone of haemopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of bone marrow with scar tissue
What is leukoerythroblastic change?
Nucleated red blood cells and primitive white cells seen in the peripheral blood
How does myelofibrosis present?
Marrow failure (bleeding, infection)
Splenomegaly
Hypercatabolism
In which conditon do you see teardrop shaped red blood cells?
myelofibrosis
What important changes to the blood film do you see in myelofibrosis?
Leucoerythroblastic change
Tear drop red blood cells
What important changes do you see on a trephine biopsy of myelofibrosis?
Fibrosis
What is the treatment for myelofibrosis?
Supportive (transfusion, platelets)
Allogenic stem cell transplant
JAK2 inhibitors
