Anaemia and Haemoglobinopathies Flashcards
In what conditions is there a decrease reticulocyte count?
iron/B12/folate deficiency, bone marrow disease, anaemia of chronic disease
In what conditions is there an increased reticulocyte count?
haemolysis
thalassaemia
blood loss
What are the causes of microcytic hypochromic anaemia?
iron deficiency thalassaemia anaemia of chronic disease lead poisoning sideroblastic anaemia
What are the causes of normocytic normochromic anaemia?
renal failure acute blood loss primary bone marrow failure drug induced anaemia of chronic disease
What are the causes of macrocytic anaemia?
B12/folate deficiency cytotoxic drugs alcohol myelodysplasia hypothyroidism chronic liver disease
What does pencil cells on a blood film usually indicate?
iron deficiency
What does spherocytes on the blood film usually indicate?
haemolysis
What is ferritin?
the main cellular storage form of iron
What is the role of hepcidin?
to regulate intestinal iron absorption and the distribution of iron to tissues
high hepcidin decreases dietary iron uptake
What causes low hepcidin levels?
iron deficiency
hypoxia
erythropoesis
What causes high hepcidin levels?
iron excess
inflammation
What happens to hepcidin in chronic haemolytic anaemias and thalassaemias?
hepcidin is decreased despite iron overload
What happens to hepcidin in haemochromatosis?
innappropriately suppressed
What are the findings on iron studies for iron deficiency anaemia?
decreased serum iron
increased serum transferrin and total iron binding capacity
decreased transferrin saturation
decreased serum ferritin
What test is useful to differentiate anaemia of chronic disease with iron deficiency and inflammation?
soluble transferrin receptor
only elevated in iron deficiency
What is the structure of haemoglobin?
heterotetramer consisting of two pairs of globin polypeptide chains
What makes up haemoglobin A?
two alpha and two beta chains
What makes up haemoglobin A2?
two alpha and two delta chains
What makes up haemoglobin F (fetal haemoglobin)?
two alpha and two gamma chains
What causes a left shift of the oxygen dissociation curve?
decreased temperature, decreased 2-3 DPG, decreased H+, CO
What causes a right shift of the oxygen dissociation curve?
increased temp, increased 2-3 DPG, increased H+
What makes up haemoglobin H?
beta tetramer
Why is haemoglobin H unable to deliver oxygen to tissues?
because it has high affinity for oxygen (won’t give it up at normal tissue oxygen partial pressures)
Where are the haemoglobin genes?
alpha gene cluster on short arm of chromosome 16
beta gene cluster on chromosome 11
What is the underlying genetic cause of sickle cell anaemia?
homozygous valine for glutamic acid in the 6th position of beta chain
What is the underlying genetic cause of sickle cell disease?
valine for glutamic acid on one beta chain with coinheritence of beta thalassaemia gene
What causes haemoglobin E?
G->A substitution in codon 26 of the beta globin gene
What causes alpha thalassaemia?
usually deletion of one or both alpha globin gene
What are the consequences of thalassaemia?
increased haemolysis ineffective/increased erythropoesis iron overload extramedullary haemopoesis bony expansion (frontal bossing) high output cardiac failure osteoporosis endocrinopathy renal impairment
What is the initial screening test for thalassaemia?
HPLC
What is the management for transfusion dependent thalassaemia?
tranfuse to Hb > 100 to reduce erythropoesis drive
iron chelation
What used to be the major cause of death in thalassaemia?
cardiomyopathy from iron overload
