10 - Haemopoiesis Gone Wrong Flashcards
What are the different causes of polycythaemia?
Polycythemia is where the volume percent of erythrocytes in the blood exceeds 52% (male) or 48% (female)
What are myeloproliferative neoplasms?
- Group of diseases of the bone marrow in which excess cells are produced
- Genetic mutations in the myeloid lineage
What is a primary cause of polycythemia?
- Polycythaemia Vera
- Myeloproliferative neoplasm in bone marrow leading to increase RBC
- Mutation in JAK2 (tyrosine kinase) allowing multipotent stem cells to survive longer and proliferate continuously
What are some clinical signs of polycythemia vera?
- Signs due to blood being thicker than normal
- Gout due to purine metabolism
- Pruritis is itching
How do you treat polycythemia vera?
- Venesection to keep Hct <0.45
- Aspirin to stop thrombosis
- Manage CVS risk factors
- Hydroxycarbamide (inhibits DNA synthesis) if poor tolerance to venesection, splenomegaly or progressive disease (e.g night sweats and weight loss)
What are secondary causes of polycythemia?
- Chronic hypoxia producing EPO (e.g smoking and high altitudes)
- Renal disease
- Tumours secreting EPO
What are the different causes of thrombocytosis?
What is primary thrombocytosis?
- Essential thrombocythaemia
- Blood cancer by myeloproliferative neoplasm in the bone marrow
- JAK2 mutations or thrombopoietin receptor mutations
What are the most common symptoms of essential thrombocythemia and how can it be treated?
Symptoms:
- Numbness in extremities
- Thrombosis (mainly arterial so peripheral gangrene/stroke)
- Disturbances in hearing and vision
- Headaches
- Eryhromelalgia in hands and feet
Treatment:
- Low risk: aspirin
- High risk (for bleeding/clotting): hydroxycarbamide
What is inherited thrombocytopenia?
- Rare inherited syndrome
- Fanconi anaemia, Bernard-Soulier syndrome and Alport syndrome
What is acquired thrombocytopenia symptoms and the causes?
- Bleeding gums
- Nosebleeds
- Heavier/longer menstrual periods
- Petechiae on feet, shins, forearms
What are immune thrombocytopenia called and what are the triggers?
- Immune Thrombocytopenic Purpura
- Antiplatelet auto-antibodies and T cell activity against platelets
- Trigger can be an acute infection, rheumatoid arthritis, SLE, lymphoid cancers, HIV
- Fatal intracranial haemorraghe
What are treatments of ITP and why is it important to catch early?
- Corticosteroids, immunosuppressive drugs, IV human immunoglobulin, splenectomy, thrombopoietin receptor agonists
- Important it is recognised as a severe thrombocytopenia as treatment very different to alternative causes, e.g bone marrow failure
What is primary and secondary myelofibrosis?
Primary: Myeloproliferative neoplasm where proliferaiton of mutated stem cells leads to reactive bone marrow fibrosis and then replacement of marrow with scar tissue. JAK2 associations
Secondary: disease developed as consequence of polycythemia vera and essential thrombocythemia
What are some symptoms of primary myelofibrosis?
- Hepatosplenomegaly (extramedullary haemopoiesis)
- Bruising
- Fatigue (and other anaemia symptoms)
- Weight loss
- Fever
- Increased Sweating
- Portal hypertension
How do you treat primary myelofibrosis?
- Supportive like hydroxycarbamide, folic acid and allopurinol (decrease high uric acid with chemotherapy)
- Sometimes splenectomy and blood transfusion
- Ruxolitinib: JAK2 inhibitor reduces spleen volume and improve symptoms
POOR PROGNOSIS - ABOUT 5 YEARS
What is chronic myeloid leukemia?
- Unregulated growth of myeloid cells in bone marrow leadng to accumulation of granulocytes and myelocytes in the blood
- Associated with Philadelphia chromosome (9 and 22)
- BCR-ABL gene causes tyrosine kinase activity that leads to proliferation, differentiation and inhibition of apoptosis
What is a treatment of chronic myeloid leukemia?
Drug inhibits ATP binding site of tyrosine kinase so cannot proliferate the cell further
What is aplastic anaemia?
- Damage to bone marrow leading to pancytopenia. Bone marrow can be empty
- Can be genetic, autoimmunity, radiation, certain drugs or infiltration of bone marrow
- Often die due to bleeding or neutropenic infections
What are the causes of thrombocytopenia?
