Haemolytic Anaemia and Haemoglobinopathies Flashcards
What are Haemoglobinopathies
Compare 2 types
Inherited disorders in globin genes
- Sickle cell disease: Abnormal globin chain variants with altered stability and/or function.
- Thalassaemia: Reduced/ absent expression of normal globin chains
Compare the proportions of HbF and HbA before and after birth
Before birth, HbF is the main form but HbA is also synthesised. After birth, HbA steadily increases to become the dominant form
How many alpha-globin genes do humans have
How many from mother and father
In alpha thalassemia, how many globin chains can be deleted
4 genes, 2 from mum 2 from dad
1-4
If only one Alpha-globin gene is deleted, what disease occurs
How severe is the anaemia
Silent carrier state
Asymptomatic
If only 2 Alpha-globin genes are deleted, what disease occurs
How severe Is the anaemia
Which genes are deleted
What other kind of thalassaemia does it resemble
Alpha-thalassaemia trait
Minimal/ no anaemia
Both genes of one chromosome/ one gene on each chromosome
Beta-thalassaemia minor/ trait
If only 3 Alpha-globin genes are deleted, what disease occurs, How severe is it
What forms and how do RBCs appear
Which other form of thalassaemia is resembled
HbH disease, moderately severe
Beta-globin tetramers (HbH) form-> Hypochromic microcytes + target cells + Heinz bodies
Beta-thalassaemia intermedia
If 4 Alpha-globin genes are deleted, what disease occurs, How severe is it
What forms and why is this bad
Hydrops fetalis, severe usually results in death in utero
Hb Bart (Tetramers formed from excess Y-globin) in foetus forms, can’t deliver O2 to tissues
What causes Beta thalassaemia
What do Beta0 and Beta+ genes denote
Beta-globin gene mutation (Rather than deletion)
Beta0 denotes absence of chain production
Beta+ denotes reduced chain production
How severe is Beta-thalassaemia minor/ trait
What does it resemble
Describe its genotype
Usually asymptotic with mild anaemia, resembles Alpha-thalassaemia trait
Heterozygous with one normal, one abnormal gene (B0/B) or (B+/B)
How severe is Beta-thalassaemia intermedia
What does it resemble
Severe anaemia (Not enough to need regular transfusions) Resembles HbH disease
How severe is Beta-thalassaemia major
When does it manifest and why?
Describe its genotype
Severe, requires transfusions
6-9 months after birth, as HbA becomes dominant
Homozygous (B0/B0 OR B+/B+)
Explain 5 consequences of thalassaemia
- Extramedullary haemopoiesis-> Splenomegaly and heptaomegaly
- Expansion of haematopoiesis into bone cortex-> impaired growth and skeletal deformities
- Reduced oxygen delivery-> EPO stimulation
- Iron overload (due to excessive absorption due to infective haematpoiesis and repeated blood transfusions)
- Reduced life expectancy
Name 4 treatments for thalassaemia and one preventive measure
- Red cell transfusion from childhood
- iron chelation (delays iron overload)
- folic acid
- holistic care to manage complications
- Pre conception counselling and antenatal screening
What is sickle cell disease
What is the abnormality
What is the mutant Haemoglobin called
Inherited disease in which Beta-globin gene is mutated
Glutamic acid substituted by valine
HbS
Compare the outcomes of
- Heterozygous HbS
- Homozygous HbS
- Mild asymptomatic anaemia
2. Sever sickling syndrome
Why is sickle cell anaemia usually well tolerated
When do problems occur and how
What happens when this occurs repeatedly
HbS gives up O2 to tissues more readily than HbA
In low oxygen state, as deoxygenated HbS forms polymers which cause cell to form a sickle shape
Cells become irreversibly sickled and cause occlusion in vessels
Identify 5 possible conditions caused by Sickle Cell Anaemia
- Splenic atrophy
- Avascular necrosis
- Acute chest syndrome
- Stroke
- Priapism (painful erection)
What is the normal lifespan of an RBC
In which 2 regions can haemolysis occur
120 days
Intravascular (Vessels)
Extravascular ( Spleen + RES)
What are 3 types of Sickle Cell Crisis
- Haemolytic
- Aplastic ( Bone marrow stops working)
- Vaso-occlusive (Most common, painful bone crisis)
What are 2 types of haemolytic anaemia and in which type are cells more fragile
What are 3 lab findings of Haemolytic anaemia
Inherited- More fragile
Acquired
Raised reticulocytes
Raised bilirubin
Raised LDH (Lactase Dehydrogenase)
What are 4 causes of inherited haemolytic anaemia
What are 5 causes of acquired haemolytic anaemia
Inherited:
- Glycolysis defect
- G6PDH deficiency
- Membrane protein defect
- Hb defect
Acquired:
- Mechanical damage
- Heat damage
- Enzymatic damage
- Oxidant damage
- Antibody damage
When is haemolytic anaemia more severe than chronic disease
What are 3 outcomes
If Hb is very low/ Hb falls suddenly
- Bilirubin accumulation-> jaundice
- Bilurubin accumulation->Pigment gallstones
- Splenomegaly
What are 2 outcomes of massive sudden haemolysis
What are 2 signs of jaundice
- Cardiac arrest (lack of oxygen)
- Hyperkalemia (Released intracellular contents)
- Yellow discolouration of skin and sclera
- Dark urine (conjugated bilirubin)
What are 3 inherited defects in cell membrane structure
Hereditary Spherocytosis
Hereditary Elliptocytosis
Hereditary Pyropoikilocytosis
In Hereditary Elliptocytosis, which protein is most commonly defected
Which other 3 can be defected
Spectrin
Glycophorin C
Band 3
Band 4.1
In Hereditary Pyropoikilocytosis, which protein is defected
What add cells abnormally sensitive to
Spectrin
Heat
Explain the 2 classes of Autoimmune Haemolytic Anaemia
Warm (IgG) or Cold (IgM) depending on the temp. antibodies react best at
