Thalassaemia Flashcards
Is it autosomal recessive or dominant?
In simple terms, what is thalassaemia?
Recessive
Globin chains are not produced properly
What type of Hb does it affect?
What is wrong with the Hb?
HbA
There is an absence or dysfunction of the alpha or beta globin chains on the HbA molecule
Alpha-thalassaemia:
What does this lead to? - 2
Why does this typically present in new borns or foetuses?
How many alpha globing genes are there?
Impaired oxygen transport
Extravascular haemolysis
As alpha chains are required from the first trimester whereas Beta chains become more important as around 6 months or adulthood.
4 genes so you can have 1 faulty gene and still be asymptomatic
Beta-thalassaemia:
What does this cause a failure in?
What does the build-up of alpha chains cause?
Why do they get bone growth?
Why do they get iron overload?
Failure of erythropoiesis
Cell destruction - haemolysis
Due to compensatory hyperplasia from extra medullary haematopoiesis (increased immature RBCs)
As increased iron absorption is stimulated even though the body finds it hard to get rid of iron
What dictates the severity of the disease?
The number of alleles affected out of 4
Where is Beta-thalassaemia common in?
Where is Alpha-thalassaemia common in?
Which one is more common?
The Mediterranean***
Middle east
Central and South Asia
China
South-East Asia
Africa
India
Beta - T
Presentation:
Why happens to most with alpha-T?
S+S of haemolytic anaemia?
Why do they get a cardiac flow murmur?
Why do they get splenomegaly? - usually on its own in alpha - T
Why do they get hepatosplenomegaly?
They don’t survive pregnancy or early life
Fatigue
SOB
Pallor
Jaundice (more common in B)
Due to high output
Thalassemia is often accompanied by the destruction of a large number of red blood cells and the task of removing these cells causes the spleen to enlarge. Splenomegaly can make anaemia worse, and it can reduce the life of transfused red blood cells.
Ineffective erythropoiesis leads to activation of extramedullary erythropoiesis in areas such as the spleen, liver, lymph nodes, and the thorax. Hepatomegaly can result from a number of mechanisms; extramedullary erythropoiesis, hepatitis due to chronic transfusion-associated infections, and iron overload.
Splenomegaly same as above
Presentation:
What does it cause in children?
Facial dysmorphia (more common in beta):
- What features could they have?
- Why does this happen?
Failure to thrive
Growth restriction
Frontal bossing
Maxillary hypertrophy
Large head
Thalassemia can make your bone marrow expand, which causes your bones to widen. This can result in abnormal bone structure, especially in your face and skull. Bone marrow expansion also makes bones thin and brittle, increasing the chance of broken bones.
Investigations:
Preconception screening (questionnaire +/- DNA testing) of both parents in at risk populations.
Bloods:
- FBC - what will you find?
- MCH is also low - what is this?
- Why are reticulocytes raised?
- Why may iron and ferritin be raised (iron overload)?
- Why would you expect to be raised in the LFTs?
Low Hb
Low MCV
Low MCH - The mean corpuscular haemoglobin, or “mean cell haemoglobin” (MCH), is the average mass of haemoglobin (Hb) per red blood cell (RBC) in a sample of blood.
In anaemia, the reticulocyte count will be abnormal because the levels of red blood cells and haemoglobin are low. Also, reticulocytes make up a higher percentage of the blood count in anaemia, which makes the reticulocyte count falsely high.
Due to frequent transfusions
In beta thalassaemia major multiple blood transfusions, ineffective erythropoiesis and increased gastrointestinal iron absorption lead to iron overload in the body. Iron overload impairs the immune system, placing patients at greater risk of infection and illness.
Raised unconjugated BR
Raised liver enzymes in iron overload
Investigations - Diagnosis:
What can be used to look at the Hb itself to confirm the diagnosis?
Gap-PCR can also be used. What is it?
Haemoglobinopathy screen - Hb electrophoresis
Gap-PCR detects deletion that might be missed by DNA sequencing. Specific primers are designed to flank a known deletion. The principle of gap-PCR is based upon the inability of the primers to generate a PCR product unless a deletion joins the flanking sequences together.
Investigations - Imaging:
Why is a skull XR needed?
Why is a chest R needed?
Why is the abdo US needed?
Why is an ECG and echo needed?
Bony abnormalities
Rib deformities
Cardiomegaly
Organomegaly
Cardiac function
Management:
Asymptomatic carriers require no specific Rx but they should just avoid supplements.
Tranfusion indications?
Iron chelation - what is it?
What drug can be given if there is iron overload? - D
When is a splenectomy indicated?
What is the last resort if severe and transfusion-dependent?
What drug may help beta chain abnormalities?
Symptomatic anaemia or aplastic crisis
Iron chelation therapy is the removal of excess iron from the body with special drugs. Chelate is from the Greek word “claw”.
Desferrioxamine
Hypersplenism with increasing transfusion requirements
Bone marrow transplantation
Hydroxycarbamide
Complications:
What does iron overload cause and why?
What GI disease are they likely to get?
Why do they get hypersplenism or hypertrophy?
What virus may cause an aplastic crisis?
Iron deposits in organs
Liver, heart, pancreas, pituitary gland
When the spleen breaks down a red blood cell in a person with thalassemia, that iron often stays inside the spleen rather than being reused. Thalassemic red blood cells often also get stuck in the spleen because they’re small and misshapen. Both of these factors can cause the spleen to become enlarged.
Parvovirus B19 infection - SAME AS SICKLE CELL - HAPPENS IN INHERITED ANAEMIAS
