Haematology Flashcards
What type of tyrosine kinase receptor is mainly implicated in myeloid cells?
JAK2
What are the growth factors for RBCs and platelets respectively?
Erythropoietin and Thrombopoietin.
What does STAT stand for and where is it placed in the cascade of cell proliferation?
Signal transducer and activation of transcription.
When the growth factor binds to JAK2, this leads to phosphorylation and activation of STAT, which leads to trasncription of genes involved in cell porliferation.
Which cell types are overproduced in PCV? What are the EPO levels in PCV?
There is overproduction of RBCs. There often is also increased production of platelets and granulocytic cells.
EPO levels are suppressed, as RBC produciton is independant of levels that usually control erythropoiesis.
How does PCV present?
- Often incidental finding on routine blood test
- Symptoms of hyperviscosity/↑platelets:
- Headache/light headedness
- Stroke/TIAs (+ thrombosis all over)
- Visual disturbances (+retinal vein engorgement)
- Fatigue
- Dyspnoea
- Symptoms of ↑histamine (as there are ↑mast cells/basophils)
- Aquagenic pruritus
- Peptic ulceration
- Splenomegaly
- Plethora
- Gout (↑ cell turnover ↑uric acid production)
What investigations are indicated in a patient with suspected PCV?
- FBC (↑Hb, ↑Hct, ↑Platelets, noramal or ↑ WCC)
- Isotype dilution indicating ↑plasma volume
- BM aspirate ↑cellularity (mainly erythrocytes, megakaryocytes) MATURE cells
- EPO: low
- JAK2 V617F mutation (DAGNOSTIC)
Name causes for primary and secondary erythrocytosis.
Erythrocytosis is the isolated incrased in RBCs (thereby differing from PCV).
Primary Erythrocytosis is due to a mutation in the EPO receptor. Thoght to be on Exon 12.
Secondary erythrocytosis due to chronic hypoxia (e.g. hgih latitude living, chronic lung disease)
What are the principles of treatment for PCV?
Reduce Viscosity:
- Venesection
- Cytoreductive therapy (hydroxycarbamide)
Reduce thrombosis risk:
- Aspirin
- Keep platelets <400 x10^9
What are the principles of treatment for primary erythrocytosis
Venesection only.
What is essential thrombocythaemia (ET)?
Chronic myeloproliferative disease involving the megakaryocyte lineage.
How does ET present?
- 50% incidental finding on routine blood
- Thrombosis:
- Arterial: CVA, gangrene, TIAs
- Venous: DVTs, PEs
- Bleeding (mucous membranes, cutaneous)
- Headaches, dizziness, visual disturbances
What are the diagnostic criteria for ET?
- >600 x10^9 consistently
- Abnormal megakaryocytes and clustering
- Absence of evidence for reactive thrombocytosis (i.e. no infection/inflammation, no neoplasia, no splenectomy)
- Symptoms + JAK2 V617F mutation
What are the apporaches to treating ET?
- Aspirin
- Cytoreductive therapy
- Hydroxycarbamide
- Anagrelide (specific platelet inhibition)
- alpha-IFN in pregnancy
How doeshydroxacarbamide work?
It’s an antimetabolie, therefore also causes suppression of other cell types.
It is thought to be mildy leukaemogenic.
What is myelofibrosis?
It is a clonal myeloproliferative disease associated with reactive BM fibrosis and extramedullary haematopoiesis.
The “reactive” refers to the fact that it is due to cytokines produced by the abnormal haemotopoietic cell clones that lead to fibrosis.
Idiopathic myelofibrosis means the disease is of unkown origin, but it can also be secondary to PCV or ET.
