Haemolytic Anaemia And Haemoglobinopathies Flashcards
What is thalassaemia?
Reduced RATE of synthesis of normal a or B globin chains
What is sickle cell disease?
Synthesis of an abnormal haemoglobin
Where is thalassaemia most common?
B - South Asia, Mediterranean and Middled East
A - Far East
What causes anaemia in thalassaemias?
Low level of intracellular haemoglobin accounts for hypochromic microcytic red cells.
The relative excess of the other globin chain contributes to the defective nature of the red cell.
Most of the maturing erythroblasts are destoryed within the bone marrow and there is excessive destruction of mature red cells in the spleen.
So.. as well as defective Hb production this is a form of haemolytic anaemia also as the red cells are destroyed.
Not making enough and red cells are more rapidly destroyed…
What are the four versions of a-thalassaemia? (1-4 chains deleted)
Silent carrier state
- Deletion of a single a-globin gene
- It is asymptomatic, without anaemia
a-Thalassemia trait
- Deletion of two a-globin genes
- It may affect both genes of one chomosome or one gene of each chromosome
- There is minimal or no anaemia and no physical signs; clinical findings are identical to those of b-thalassemia minor (microcytosis and hypochromia)
Haemoglobin H (HbH) disease
- Deletion of three a-globin genes.
- Tetramers of B-globin called HbH are formed.
- There is moderately severe anaemia, resembling B-thalassemia intermedia (microcytic, hypochromic anaemia with target cells and Heinz bodies in the blood film).
Hydrops fetails
- Deletion of all four a-globin genes
- In the foetus, excess of y-globin chains form tetramers (Hb Bart) that are unable to deliver the oxygen to tissues. Usually intrauterine death.
What is the difference between B-thalassaemia minor and B-thalassaemia major?
Major:
- Severe tramsfision-dependant anaemia that first becomes manifest 6-9months after bith as synthesis switches form HbF to HbA
- Homozygous
Minor:
- Usually asymptomatic with mild anaemia
- Heterozygous
- One normal gene
What are the consequences of Thalassemia?
Extramedullary haemopoiesis is an attempt to compensate but it results in splenomegaly, hepatomegaly and expansion of haemopoiesis into the bone cortex… if the patient isn’t treated with blood transfusions, it can result in skeletal abnormalities.
Reduced oxygen delivery leads to stimulation of erythropoietin (EPO) which further contributes to the drive to make more defective red cells.
Iron overload is major cause of premature death and occurs due to:
- Excessive absorbtion of dietary iron due to ineffective haematopoiesis
- Repeated blood transfusions required to treat the anaemia.
What is the treatment of thalassaemia?
Transfusions of red cells from childhood
Iron chelation - if not, cardiac failure. Can now be given orally but before used to be a drip Folic acid
Immunisation
Holistic care - cardiology, endocrine, psychological, opthalmology, input to pick up and manage complications
Stem cell transplantation in some
Pre-conception counselling fo at risk couples and antenatal screeening.
What is sickle cell?
Inheritance of the sickle B-globin chain.
A point mutation causes substitibtion of valine for glutamic acid in position 6 in the B-chain.
HbSS = homozygous sickle cell anaemia, is most common cause of severe sickling syndrome.
HbS can also be co-inherited with another abnormal Hb e.g. HbC (HbSC) or B-thal to cause a sickling disorder.
HbS carrier state causes a mild asymptomatic anaemia and is found in up to 30% of W african people as it confers protection agaisnt malaria.
When do problems occur in sickle cell disease?
Symptoms of anaemia are usually mild as HbS readily gives up oxygen in comparison to HbA
Problems come in low oxygen state when deoxygenated HbS forms polymers and the red cells form a sickle cell shape.
Irreversibly sickled red cells are less deformable an can cause occlusion in small blood vessels - ‘sticky’
What problems occur for people with sickle cell?
- Chronic skin ulceration
- Osteomyelitis
- Avascular neucrosis
- Reduce conc. ability and infarcts in a kidney
- Tiny spleen - as infarcted lots
- Excess of bilirubin, can lead to gall stones Iron overload
- Acute chest syndrome
- Stroke - thrombosis in small circulation of brain
- Retinopathy, blindness
- Iron overload in heart and liver
What are the most common things people with sickle cell suffer form?
- Vaso-occlusive (painful bone crises, Organ chest, spleen))
- Aplastic (often triggered by parvovirus infection)
- Haemolytic
End organ damage as a result of chronic or acute thromboses or oxygen deprivation.
How does sickle cell effect a patient?
Diagnosed - Child 1-2 years old
Childhood - Limitations, can’t run around as much as friends. Excruciating pain when have sickle cell crises. Regular hospital visits. S
ickle cell crises - Scary. Can happen anywhere. Excruciating pain - need to get to hospital. Get worked up and need to calm down.
Pain - Like having swords pierced though and twisted. On same level as pregnancy pain.
Education - Not as bad in school. College worse as stress - In college 60% of time. Had to work harder to get where needs to be.
Triggers - Cold, Infection, Psychological stress
Treatment - Penicillin, Folic acid (as spleen disintegrated), Hydroxycarbomide (but side effects)
Psychological - Won’t go too far from hospital, scared, overthink everything,
Red cell exchange - hospital every two months, heats up and exchanged his RBCs for normal
RBCs - Makes him feel better But, struggled to find vein so now has a port,
3 important things to know - Know how to treat a patient in crisis, Put yourself in mind of patient, encourage patient to get better (extra mile).
What are the consequences for people with sickle cell disease?
Reduced life expectancy - 67 yrs if HbSS. Common cause of death: Stroke, Multi-organ failure, acute chest syndrome.
Acute and chronic pain problems.
Stroke, Cognitive and neurological kidney failure, Priapism (prolonged painful errection)
What is haemolytic anaemia?
Results from, abnormal breakdown of RBCs (haemolysis).
The bone marrow can compensate for a decrease in lifespan by increasing red cell production but has capacity to increase by around 6 times so if rate of destruction exceeds this anaemia develops.
What are the classifications of haemolytic anaemia?
