Thalassemia Flashcards
Inheritance of thalassemia
Autosomal recessive
Affect of thalassemias on RBC
Anaemia
Microcytic RBC
Why do thalassemias cause anaemia
Shsortened RBC half life and bone marrow cant keep up with RBC production
What can increased RBC destruction cause
Jaundice
Increased likelihood for gallstones
When does alpha thalassemia start affecting patient
First trimester of pregnancy to adulthood as require alpha chains from foetus for Hb
When does beta thalassemia start affecting patient
After 4-5 months old - when beta chains start being importnat for Hb
What genetic abnormality causes beta thalassemia major
2 abnormal genes
Situations that can cause beta thalassemia intermedia
2 mildly abnormal genese
One very abnormal gene
What is dominant negative beta thalassemia
Where the one abnormal beta chain protein inhibits function of the normal protein
What beta thalassemia diseases require regular transfusions
Major = lifelong
Intermediate = regular potentiall required
What will one gene abnormality in beta chain cause?
beta thalassemia trait - asymtpomatic
What is the normal number of genes for encoding alpha chains
4
What does alpha thalassemia severity depend on
how many genes lost
What does 0 working alpha chains cause
Hb barts or hydrops fetalis - incompatible with life
How can try and prevent alpha thalassemia complete causing hydrops fetalis
Intrauterine transfusion and post natal bone marrow transplant
What does 3 working alpha genes cause
Asymptomatic, no anaemia, ay have slight miscrocytic RBC
What causes HbH and what are the clinical features
1 working alpha gene
Microcytosis Marked anaemia
Surprisingly well often
What does unbalaced/ineffective Hb stimulate
Production of more Hb
Iron absorpiton (causes Fe overlaod)
What does overporduction of Hb cause
Extramedullay haemotopoeisis
Bony deformity
What can bony deformity in thalassemia present as
‘hair on end’ skull radiograph
Thalassemic face - deformity
Risk of fractures
Treatment for beta thalassemia symptomatic or physiological
1st line - blood transfusions - ALL beta majors
Hydroxycarbamide - beta intermedia
Lutacerpt- decrease transfusion burden in some
Bone marrow transplant
Gene therapy
Genetic counselling - select unaffected embryos
Iron chelation to mitigate overload effects
Complications of thalassemia
Iron overlaod from regular blood transfusions
iron overload complications (from transfusions)
Endocrine - diabetes, stunted grwoth
Cardiac arrhythmias
Hepatic toxiity - cirrhosis, HCC
Summary of hereditary spherocytosis
- Often asymptomatic until increased O2 requirement
- Treatment supportive
- Folate replacement
- Increased thrombotic risk
- Increased risk of pulmonary HPTN
G6PD deficinecy summary
- Acute haemolysis when exposed to oxidants
- Classic = broad beans 9fava beans), many other drugs also cause haemolysis
- Antimalarials, antibiotics, chemotherapy
X linked (can affect females if both chromosomes affected)
- Antimalarials, antibiotics, chemotherapy
What do all inherited anaemias increase risk to?
- Specific risk from parvovirus B19 infection
- Can cause temporary halt of RBC production -. profound anaemia
What diseases cause iron overload due to transfusions but canot venesect as transfusion dependent eg may need iron chelation
, beta thalassemia major, severe beta thalassemia intermedia, sickle cell anemia, myelodysplasia, aplastic anemia
Meds for thalassemia iron chelation
Deferixamine
Deferrasirox
HBH globin cells present
moderate anaemia and microcytic, hypochromic red cells anisopoikilocytosis (red blood cells of varying and abnormal sizes and shapes), teardrop cells and basophilic stippling.
Test for thalassemia
haemoglobin electrophoresis
When give folic acid supplementation
High turnover of RBC eg haemolysis
Haemoglobin electrophoresis in alphA HbH disease
Reduced HbA
Increased HbH = large amounts
Haemoglobin electrophoresis in beta thalassemia trait
raised level of haemoglobin A2 (HbA2)
Features of beta thalassemia major
Severe anaemia
Bony expainsion
Hepatosplenomegaly and jaundice
What surgery can reduce blood requirement in beta thalassemia major
Splenectomy
Investigation results in beta thalassemia majro
Full blood count: microcytic anaemia
Liver function tests: isolated hyperbilirubinemia
Ferritin or iron studies: normal iron levels, differentiating thalassaemia from iron deficiency anaemia
Blood film: hypochromic, microcytic anaemia, nucleated red blood cells, target cells, polychromasia (reticulocytes) and basophilic stippling
Haemoglobin electrophoresis or HPLC: absence of HbA, both HbF and HbA2 are elevated
Screening for thalassemia
Pregnant women are offered a blood test before they reach 10 weeks gestation to identify carriers of thalassaemia.
If mum is carrier father offered testing. If both parents -> chorionic villus sampling or amniocentesis->thalassaemia status.
Testing for thalassaemia is also included in the newborn blood spot for babies 5-8 days old.
What infections does splenectomy increase the risk of
pneumococcal, Haemophilus and meningococcal infection
Infections seen in iron overlaod
klebsiella, yersinia and fungal infection
Blood transfusion complications if regular
Infection
Osteoporosis
Transfusion reactions
Alloimmunisation - transfused patient develops antibodies against red cell antigens, difficulties crossmatching and trasnfusion reactions
Endocrine complications: due to iron overload, patients can develop delayed sexual maturation, infertility, thyroid dysfunction and parathyroid dysfunction.
Cardiovascular complications: iron overload increase the risk of arrhythmias and heart failure due to iron-induced cardiomyopathy.
Thrombosis: thalassaemia increases the risk of thrombosis.
Other complications: gallstones, leg ulcers, gout and skin bronzing due to iron overload
