7) Anaemia Flashcards
What can be the cause of reduced erythropoiesis?
Empty bone marrow - after chemo, toxic insult (parvovirus), aplastic anemia
Marrow infiltration by cancer cells of fibrous tissue
CKD
What are the features of myelodysplastic syndromes?
Production of abnormal clones of marrow stem cells
Macrocytic anaemia
How can myelodysplastic syndromes be diagnosed?
Microscopy of blood cells and bone marrow cells
Genetic testing on marrow cells
In which conditions can there be dyserythropoiesis?
Renal disease
RA
SLE
IBD
What are the features of dyserythropoiesis?
Iron is not released for use in bone marrow
Reduced RBC lifespan
Marrow shows lack of response to EPO
What haemoglobin abnormalities can lead to anaemia?
Lack of iron - IDA
Deficiency in building blocks for DNA synthesis - Vit B12/folate
Mutations in proteins encoding globin chains
Describe the features of red cells in iron deficient anaemia:
Microcytic anemia
Variation is size and shape of RBCs
Hypochromia
Why is there macrocytic anaemia in B12 and folate deficiency?
Deficiency causes DNA synthesis to be impaired so cell cycle can’t progress from G2 to M. Continuing growth without division
How is B12 delivered to bone marrow from oral intake?
Combined with intrinsic factor, and complex binds to ileum allowing absorption of B12
In blood B12 binds to transcobalamin which delivered it to bone marrow and other tissues
What can be the causes of vitamin B12 deficiency?
Dietary deficiency - vegan
Lack of intrinsic factor - pernicious anemia
Disease of ileum - Crohn’s
Lack of transcobalamin - congenital
Where is folate absorbed in the gut?
Duodenum and jejunum
What are dietary folates converted into once absorbed?
Methyltetrahydrofolate
What can be the causes of folate deficiency?
Dietary
Increased use: pregnancy, haemolytic anaemia
Disease of duodenum and jejunum - coeliac, Crohn’s
Methotrexate
Alcoholism
What other problems can occur as B12/folate deficiency progresses?
Neurological disease - focal demyelination
Depression and dementia
Describe the features of sickle cell disease:
Point mutation - substitution of valine for glutamate in beta chain of Hb
Sickle shape of RBCs when deoxygenated
How can sickle cell anaemia lead to sickle cell crisis?
Repeated cycles of deoxygenation cause irreversibly sickled RBCs which can cause obstruction in capillaries
Which groups are thalassaemias particularly prevalent in?
South Asia, Mediterranean, Far East
Describe the features of red cells in thalassaemia:
Hypochromic and microcytic
Anisopoikilocytosis, target cells, nucleated red cells
Describe some of the systemic effects of thalassaemias:
Extramedullary haemopoiesis - splenomegaly, hepatomegaly
Stimulation of EPO
Iron overload
What is the treatment for thalassaemias?
Transfusions
Iron chelation
Folic acid
Immunisation
Describe beta-thalassaemia major:
Both beta genes abnormal
6-9 months after birth - switch from HbF to HbA
Transfusion dependent
Describe beta-thalassaemia intermedia:
Severe anaemia - episodic blood transfusions
Describe beta-thalassaemia minor/trait:
Usually asymptomatic with mild anaemia
One normal gene
Heterozygous
Describe alpha thalassaemia trait:
Deletion of two alpha globin genes
Minimal or no anaemia
Describe haemoglobin H disease:
Deletion of three alpha globin chains
Tetramers of beta globin (HbH) are formed
Moderately severe anemia
Describe hydrops fetalis:
Deletion of all 4 alpha globin genes
Usually intrauterine death
What inherited abnormalities in the red cell membrane can lead to anaemia?
Hereditary spherocytosis
Hereditary elliptocytosis
Hereditary pyropoikilocytosis
Hereditary stomatocytosis
What can damage the red cell membrane and lead to anaemia?
Mechanical damage - valves, vasculitis, DIC
Heat damage - burns
Osmotic damage - drowning
What red cell enzyme defects can lead to anaemia?
G6PD deficiency
Pyruvate kinase deficiency
Where are common places to bleed causing unexplained microcyctic anaemia?
Gastric ulcer Gastric cancer Colon cancer Excessive menstruation Bladder cancer
Describe autoimmune haemolytic anaemia:
Autoantibodies bind to red cell membrane proteins and remove them from circulation
Can be warm or cold
What are some key laboratory features of autoimmune haemolytic anaemia?
Increased reticulocytes
Raised bilirubin
Raised LDH
How should we classify anaemia to allow us to identify the cause?
Mechanism
Size - micro, normo and macrocytic
Presence or absence of reticulocytosis
