Haemolytic Anaemias + Haemoglobinopathies Flashcards
What are the types of haemoglobin and their globin chain composition?
A - 2a/2B - prominent 6 months after birth
A2 - 2a/2delta
F/fetal - 2a/2gamma
What are haemoglobinopathies?
Genetic disorders which alter haemoglobin structure
Types of haemoglobinopathies
-
reduced/abscess expression of normal globin chains
e.g. thalassaemia -
abnormal globin chain variants with altered stability/ function
e.g. sickle cell
Outline the types of thalassaemias + where they are most common
alpha:
- a globin gene expression affected
- common in far east populations
beta:
- B globin gene expression affected
- common in south Asian, Mediterranean + Middle East populations
Describe the alpha globin gene cluster
4 a globin genes - 2 per parents
On chromosome 16 (think 4x4=16)
Describe the beta globin gene cluster
2 B globin chains
On chromosome 11 (think 1+1=2 > 2 chains)
Alpha thalassaemia deletion 1
- disease
- severity
- info
- disease: silent carrier state
- severity: asymptomatic
- info: carrier > no symptoms
Alpha thalassaemia deletion 2
- disease
- severity
- info
- disease: a-thalassaemia trait
- severity: minimal or none
-
info: microcytosis: smaller RBCs
Hyprochromia: less pigmaneted RBCs
Similar to B thalassaemia minor
Alpha thalassaemia deletion 3
- disease
- severity
- info
- disease: haemoglobin H disease
- severity: moderately severe
-
info: tetra of B-globin (HbH) formed
Microcytic, hypochromic
Heinz bodies , target cells
Similar to B thalassaemia intermedia
Alpha thalassaemia deletion 4
- disease
- severity
- info
- disease: Hydros fetalis
- severity: severe > intrauterine death
-
info: tetramers of y globin (HbBart) formed
Unable to deliver O2 to tissues - high affinity
Beta thalassaemia trait/minor
- severity
- genotype
- info
- severity: asymptomatic with mild anaemia
-
genotype: heterozygous - 1 normal, 1 abnormal
Bo/B or B+/B -
info: microcytic + hypochromic RBCs
Resembles a thalassaemia trait
Beta thalassaemia intermedia
- severity
- genotype
-
severity: severe anaemia
But no regular blood transfusions -
genotype: heterozygous - Bo/B
Some mild homozygous - B+/B+
Beta thalassaemia major
- severity
- genotype
- info
-
severity: severe anaemia
Regular blood transfusion needed
Iron chelation needed - genotype: homozygous Bo/Bo or B+/B+
-
info: microcytic + hypochromic RBCs
Abnormal skull bones
Hepatosplemeglay due to etramedullary
haemopoiesis
What are the consequences of thalassaemia
- extramedullary haemopoiesis > hepatosplenomegaly
- decreased O2 delivery > stimulation of EPO > more defective RBCs
- decreased life expectancy
- increased EPO > bone marrow expansion > skeletal deformities
- iron overload due to repeated blood transfusions + excessive absorption of dietary iron due to ineffective haemopoiesis
Treatment of thalassaemia
Blood transfusion
Iron chelation
Folic acid - supports EPO
Immunisation
Stem cell transplant
Holistic care
Pre-conception counselling
Outline sickle cell disease
- Autosomal recessive
-
Mutations of the B globin gene: glutamic acid > valine at position 6 (think SIXle cell anaemia)
. - HbS form polymers > sickle shape
- Repeated sickling cycle > irreversible sickle shape
- Less flexible > occluded small blood vessels
- More fragile > broken down > haemolytic anaemia
Severe consequences of sickle cell anaemia
Stroke - form occlusions
Acute chest syndrome
Splenic atrophy
Kidney infarcts
Osteomyelitis
Types of haemolysis and their location
intravascular - in blood vessels
extravascular - in spleen and wider RES
Key lab findings in haemolytic anaemia
Increased reticulocytes
Increased bilirubin > gallstones + jaundice
Raised lactate dehydrogenase
Splenomegaly
What is seen in a blood smear of a patient with severe thalassaemia?
Microcytic + hypochromic RBCs
Anisopoikilocytosis
Target cells
Nucleated red blood cells
Heinz bodies
Types of haemolytic anaemia
Inherited - defective genes
Acquired - damage to cells
Causes of inherited haemolytic anaemia
- pyruvate kinase deficiency > less ATP
- G6PDH deficiency > oxidative damage
- haemoglobin defect e.g. sickle cell
- membrane protein e..g hereditary spherocytosis
Causes of acquired haemolytic anaemia
- mechanical damage e.g microangiopathic haemolytic anaemia
- antibody damage e.g. autoimmune haemolytic anaemia
- oxidant damage
- Heat damage e.g. severe burns
- enzymatic damage e.g. snake venom
Outline hereditary spherocytosis
- Due to defect in ankyrin, spectrin, protein 4.2 or band 3 > disrupts membrane cytoskeletal interactions
- spherical shape
- less flexible + more easily damaged
Outline hereditary eliptocytosis
- Most commonly due to spectrin mutation
- elliptical shape - oval
Outline hereditary pyropoikilocytosis
- Severe form of hereditary eliptocytosis
- due to spectrin mutation
- abnormal sensitivity of RBCs to heat
Outline acquired haemolytic anaemia due to mechanical damage
- Shear stress - defective heart valves
- snagging on fibrin strands
- Cause schistocytes
- causes microangiopathic haemolytic anaemia
Outline autoimmune haemolytic anaemias
Autoantibodies bind to RBC memebrane proteins
Spleen recognises as abnormal + removes them
Can result from infection + cancers of lymphoid system
What are the 4 types of a thalassaemia?
Silent carrier state
a thalassaemia trait
HbH disease
Hydrophobic fetalis
Types of B thalassaemia
Trait/minor
Intermedia
Major
What does Bo and B+ mean?
Bo - total absence
B+ - reduction of globin production
What does band 3 do?
- Binds to ankyrin + protein 4.2 to link membrane + cytoskeleton
- facilitates Cl- + HCO3- exchange
What is protein 4.2?
- ATP binding protein
- regulates association of band 3 with ankyrin
What is ankyrin?
‘Anchoring’
Links protein to spectrin-actin cytoskeleton
What is spectrin?
Links plasma membrane to actin cytoskeleton
What is caused by a mutation in spectrin
- Hereditary spherocytosis: mutations causes less flexibility > spherocytes
- Hereditary ellipocytosis
When does B thalassaemia major manifest?
Why?
6-9 months after birth
Hbf > HbA
What is the inheritance of sickle cell disease?
Autosomal recessive
Outline the process of sickle cell disease
- HbS form polymers > sickle shape
- Repeated sickling cycle > irreversible sickle shape
