When Haemopoesis Goes Wrong Flashcards
What is polycythaemia is
Volume percent of erythrocytes in blood is high. Exceeds 52% in males and 48% in females. (High haemocrit
Causes of polycythaemia
Can be absolute where is caused by increased RBC or can be relative where caused by increase in plasma
What causes absolute polycythaemia
Primary cause- polycythaemia Vera which is myeloproliferative neoplasm in bone marrow usually due to JAK2 mutation which causes multipotent stem cells to survive longer and proliferate continuously
Secondary - EPO increase due to disease e.g renal carcinoma or in response to hypoxia e.g in high altitude
Clinical features and symptoms of polycythaemia Vera
Blood is thicker and higher percentage of haematocrit. Thrombosis Haemorrhage Headache Plethora Burning in hands and feet Puritus Gout Arthritis
Treatment of polycythaemia Vera
Phlebotomy to maintain haematocrit below 45% (removal of blood)
Aspirin due to its antiplatelet effect
Hydroxycarbamide - inhibits DNA synthesis for synthesis of new RBC
What is essential thrombocythaemia
Increase in platelets.
Causes of thrombocythaemia
Primary - myeloproliferative neoplasm where there is overproduction of platelets by megakaryocytes. Most have JAK2 mutations. Referred to as ESSENTIAL THROMBOCYTHAEMIA
Can also be due to mutations in thrombopoietin receptor
Secondary- normal bone response to extrinsic stimulus e.g infection
Symptoms of essential thrombocythaemia
Numbness of extremities
Thrombosis
Headaches
Burning pain in hands and feet (erythromelagia)
Treatment of essential thrombocythaemia
Low risk patients- aspirin to lower platelet count
High risk - hydroxycarbomide treatment
What is and what causes inherited thrombocytopenia
Rare inherited syndrome where have low platelet count
What is and what causes acquired thrombocytopenia
Low platelet count due to
Decrease in platelet production
Increase in consumption of platelets
OR increase in destruction of platelets
Symptoms of acquired thrombocytopenia
Bleeding gums, nose bleeds, heavier and longer menstrual periods, spontaneous bleeding under skin called petechia
What is primary myelofibriosis
when mutated haematopoeitic stem cells result in bone marrow fibrosis and laying down of scar tissue. also some mutated progenitor cells may leave bone marrow and colonise liver and spleen causing extra medullary heamopoeisis
what is secondary myelofibrosis
disease has developed as a consequence of polycythaemia vera or essential thrombocythaemia.
cause of myelofibrosis
mutations in JAK 2 gene often associated with disease
side effects of myelofibrosis
hapatosplenmogaly - due to extramedullary hameatopoiesis
bruising
fatigue
fever
increased sweating
portal hypertension (due to narrowing of sinusoids in liver from extra medullary haempatopoeisis)
treatment options for myelofibrosis
hydroxycarbamide folic acid allopurinol blood transfusions splenectomy ruxolitinib - inhibitor of JAK 2 reduces spleen volume
what is chronic myeloid leukaemia
a leukaemia which is more slow to cause symptoms. may just be picked up by chance on a blood count. its the unregulated growth of myeloid cells in the bone marrow leading to the accumulation of mature granulocytes (mainly neutrophils) as well as myelocytes (bone marrow cell) in blood.
what causes chronic myeloid leukaemia
often associated with chromosomal translocation called Philadelphia chromosome between chromosome 9 and 22. = oncogenic gene fusion with tyrosine kinase activity that results in proliferation, differentiation and inhibition of apoptosis.
treatment of chronic myeloid leukaemia
drugs which inhibit ATP binding site of tyrosine kinase. this drugs has rapidly improved survival rates
what is aplastic anaemia
rare disease that results in damage to bone marrow and haematopoitic stem cells leading to pancytopenia (deficiency in all 3 cell types)
causes of aplastic anaemia
genetics, autoimmunity, exposure to chemicals, drugs or radiation
