Lecture 8 (Part 2) - Myeloproliferative Disorders Flashcards
What are the clinical features of myeloproliferative disorders? (aka effects)
- Overproduction of ≥1 blood elements
- Extramedullary haemopoiesis
- Potential to develop in acute leukemia
What is the cause behind M.D?
- Specific point mutation in Janus Kinase 2 (JAK2)
- A type of tyrosine kinase (Chr9) that results in increased proliferation & survival of multipotent stem cells
(drugs target JAK2 protein)
What is polycythaemia vera? Causes? Which group usually affected?
- High haematocrit (>0.52 for men, >0.48 for women) - JAK2 mutation present in 95% patient - No reactive cause found - Median age = 60 years, both sexes affected equally
What are the clinical features of polycythaemia vera?
- Significant cause of arterial thrombosis –> stroke, myocardial infarction
- Haemorrhage of GI tract due to bursting of capillaries
- Pruritis
- Splenomegaly (pain in left upper quadrant)
- Gout: ⬆️purine metabolism
How to manage PV?
- Venesection to maintain Ht <0.45
- Aspirin (anti-platelet drug)
- Manage risk factors: hypertension, type 2 DM
- Cytoreduction drug hydroxycarbamide (inhibit DNA synthesis)
What is polycythaemia? Causes?
- Increase in circulating red cell conc which results in high haematocrit
- Cause can be relative (⬇️in plasma vol.) or absolute (⬆️red cells)
*if relative, ensure patient is not dehydrated (cause plasma decrease) - Primary = PV
- Secondary = ⬆️EPO prod. (smoking e.g)
[Physiologically appropriate = hpoxia & X app time]
Give examples of when polycythaemia is physiologically app and when X
Appropriate: (all involve hypoxia)
- Chronic lung disease
- High altitude
- CO poisoning
- Renal artery stenosis
X App: (all produce ectopic EPO)
- Hepatocellular carcinoma (cancer of liver secondary to liver cirrhosis)
- Renal cell cancer
- Uterine tumour
- Pheochromocytoma (tumour of chromaffin cells in adrenal glands)
What is essential thrombocythemia? What to screen for?
- Excess platelet
(large, excess megakaryocytes in BM) - Screen for JAK2 and CALR mutations
How to manage essential thrombocythaemia? Who are high risk patients?
- Manage cardiovascular risk factors: hypertension
- Aspirin
- High risk:
i) >60 years, platelet count >1500 or disease-related thrombosis/haemorrhage - Return platelet count to normal w hydroxycarbamide
When high platelet count is noted, what should clinicians rule out first before starting treatment?
- Rule out: infection, inflammation, haemorrhage, cancer, post-splenectomy
- **ensure condition is persistent not due to AFTER surgery
What is myelofibrosis? What does it lead to in BM?
- Proliferation of haemopoietic stem cells leads to heavy fibrotic marrow results in little space for haemopoiesis
- Blood film shows tear drop blood = squeeze out of harden BM
- Massive cause of splenomegaly/hepato due to extramedullary haemopoiesis
What is myelofibrosis an end result of? All cases of it has what?
- End result of PV
- All have pancytopenia due to marrow fibrosis and hypersplenism
What are the clinical features of myelofibrosis?
transform to leukaemia –> early death
- Those w severe disease = fatigue, sweats, weight loss
- Consequences of splenomegaly: pain in upper left quadrant, early satiety, splenic infarction
- Progressive marrow failure require transfusion
What is chronic myeloid leukaemia? What do patients present with?
- High white cell count (may be incidental finding)
- Present with splenomegaly, hyperviscosity or bone pain
- Affect adults, rare in children
- Shows excess of myeloid cells (all types
What is the treatment for myelofibrosis?
- Largely supportive & unsatisfactory
- Hydroxycarbamide (inhibit DNA synthesis)
- Folic acid
- Blood transfusions
- Splenectomy
- Ruxolitinib: inhibitor of JAK2 –> reduce spleen vol. & improve symptoms
- Used to be bone marrow transplantation (~20% mortality)
