Haem II (Thalassemia; Malaria) Flashcards
Hodgkin’s Lymphoma is often preceded by infection of which virus
Parvovirus B19
COVID
CMV
EBV
Rhinovirus
Hodgkin’s Lymphoma is often preceded by infection of which virus
Parvovirus B19
COVID
CMV
EBV
Rhinovirus
Label the type of Hb that are dominant in each stage of life [3]
Yolk Sac / A: Z2, E2
Fetal liver / B: A2, γ2
Bone marrow / C: A2, B2
What are the normal variants of Hb? [3]
What is the inheritance patten of thalassaemias? [1]
Both alpha and beta conditions are autosomal recessive
Describe the different types of alpha thalassaemias [4]
Alpha thalassemia minima:
- 1 defective alpha subunit
- Silent carriers: slightly reduced / normal MCV but no clinical symptoms
- Hypochromic and microcytic anaemia
Alpha thalassemia minor:
- 2 defective alpha subunits
- Hypochromic and microcyticnaemia
- The remaining two alpha genes produce nearly normal levels of RBCs
HbH disease:
- 3 defective alpha subunits
- Excess beta chains causes RBC membrane damage and intramedullary haemolysis AND does not release oxygen to tissues, causing increased RBC production
Hydrops fetalis, Bart’s hydrops (γ4):
- 4 defective alpha subunits
- Extreme affinity to O2: incompatible with life
Describe the pathophysiology of the different forms of beta thalassamias [3]
The gene defects can either consist of abnormal copies (that retain some function) or deletion genes (with no function in the beta-globin)
Beta Thalassaemia minor:
- Mutation in one gene
- Reduced or no production of beta chains from one gene
- Other gene still functional
- Forms HbA
- Asymptomatic
Beta Thalassaemia intermedia
- Have two defective genes OR one defective gene and one deletion gene
- Causes more significant microcytic anaemia.
Beta Thalassaemia major
- homozygous for the deletion genes
- presents with severe anaemia and failure to thrive in early childhood
.
Describe the clinical presentation of a patient with thalassemia major [4]
The bone marrow is under so much strain to produce extra red blood cells to compensate for the chronic anaemia that it expands enough to increase the risk of fractures and change the patient’s appearance. Abnormal features relating to bone changes include:
- Frontal bossing (prominent forehead)
- Enlarged maxilla (prominent cheekbones)
- Depressed nasal bridge (flat nose)
- Protruding upper teeth
What is the management of thallassemia major? [4]
Management involves;
- regular transfusions
- iron chelation
- splenectomy
- A bone marrow transplant can be curative.
Write down the genotype of Beta thalassaemia minor, intermedia and major [3]
Minor: (b+/b OR b0/b)
Intermedia: (b+/b+)
Major: (b+/b0 OR b0/b0)
Mutation leading to absent production (0)
Mutation leading to reduced production (+)
Describe the difference in anaemia between B.T. minor and major [2]
Anaemia:
- Minor: usually asymptomatic with mild microcytic anaemia with haemoglobin counts > 100 g/L.
- Major: severe transfusion-dependent anaemia. Features of pallor, dyspnoea, dizziness, lethargy. Untreated, haemoglobin may be as low as 30-40 g/L.
Describe the bone deformities that can occur in B.T major [4]
Unusual bone formation:
* Facial deformities: frontal bossing, maxilla overgrowth, prominence of upper incisors, ‘chipmunk’ facies, dental malocculsion.
* Body habitus changes: typically short limbs due to early fusion of epiphyses. Skull, pelvis, ribs and spinal changes may be seen
* Osteopaenia/osteoporosis
* Bone pain
Describe how beta thalassaemia interacts with Fe levels in the body [2]
Ineffective erythropoiesis leads to an increase in iron absorption from the gastrointestinal tract that is compounded by regular blood transfusions.
Describe three further abnormalities associated with beta thal. [3]
- Pulmonary: at risk of obstructive and restrictive defects. Some patients may develop pulmonary hypertension
- Thrombotic: beta thalassaemia intermedia and major are associated with a hypercoagulable state.
- Leg ulcers
Describe the diagnostic testing used to confirm the presence of beta thalassaemia [2]
Haemoglobin analysis:
- completed using haemoglobin electrophoresis or high-performance liquid chromatography (HPLC). Electrophoresis causes different types of haemoglobin to separate into bands. HPLC is an alternative method of determining the types of haemoglobin in blood.
- Patients with beta thalassaemia will have an increased proportion of HbA2 and HbF due to the absence of beta globin chains. Even in beta thalassaemia minor, there will be an elevation in HbA2.
Genetic testing:
- DNA testing provides a definite and precise diagnosis of beta thalassaemia. It is able to determine the type of mutation present.
Compared to alpha thal: just genetic testing
When does screening for beta thalassaemia occur? [1]
What result would indicate B.T? [1]
Antenatal screening is offered to all pregnant women within the UK. It involves concurrent assessment of different haemoglobinopathies (i.e. thalassaemia and haemoglobin variants) at 10 weeks gestation.
In beta thalassaemia, the level of HbA2 is quantified. Levels of HbA2 >3.5% is suggestive of being a beta thalassaemia carrier and further analysis of the father is required to determine the risk of beta thalassaemia in the fetus.
Describe the managment of beta-thalassaemia intermedia: non-transfusion-dependent [3]
1ST LINE:
- Transfusions at times of symptomatic anaemia
Patients with beta-thalassaemia intermedia do not usually require regular transfusions (non-transfusion-dependent thalassaemia). They are able to grow and develop at a nearly normal rate despite the moderate anaemia.
Occasionally, patients become severely anaemic and develop symptoms as a result. This usually occurs at times of major stress to the body, such as perioperatively, or during a serious illness or infection.
CONSIDER
- iron monitoring + chelation with desferrioxamine or deferasirox
PLUS
- genetic counselling
Describe the managment of beta-thalassaemia intermedia: transfusion-dependent AND beta-thalassaemia major [4]
1ST LINE:
- Regular transfusions
PLUS
- iron monitoring + chelation with desferrioxamine or deferasirox
PLUS
- genetic counselling
CONSIDER
- Splenectomy
CONSIDER
- Assessment for stem cell transplantation
Which drugs are used to manage iron overload? [3]
What is their MoA? [1]
Typical agents include Deferasirox, Deferoxamine and Deferiprone.
These chelators bind iron and increase excretion through urine and/or faeces.
Vaccinations agaisnt with pathogens are recommended in splenectomy patients? [4]
Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended.
Describe the management of hyposplenism [2]
In summary, the management can be considered to be two-fold:
Immunisations
- S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus
Antibiotic prophylaxis recommended in patients at high risk of pneumococcal infections
- oral phenoxymethylpenicillin or macrolides
- infection risk is highest in the initial years after splenectomy, all splenectomised patients are recommended to take daily antibiotic prophylaxis for the initial few years.
Name some pathologies that cause hyposplenism [5]
sickle cell anaemia (chronic damage to the spleen results in atrophy)
coeliac disease
dermatitis herpetiformis
essential thrombocythaemia
ulcerative colitis.
What are 4 blood film findings of hyposplenism [4]
Blood film: features of hyposplenism include Howell-Jolly bodies, Pappenheimer bodies, target cells and irregular contracted red blood cells.
In alpha thalassemia, the Hemoglobin H (HbH) disease results from the deletion of three alpha-globin genes. What is the recommended treatment for patients with HbH disease, according to NICE?
a) Blood transfusion
b) Hydroxyurea
c) Folic Acid supplementation
d) Hematopoietic stem cell transplantation
c) Folic Acid supplementation
