haemoglobin 4: thalassaemia

Question 1

how can thalassaemia be classified?

Answer 1

globin type affected or clinical severity (minor/trait, intermedia, major/transfusion dependent)

Question 2

where do the genetic defects arise from?

Answer 2

𝛂=chr16, ß=chr11

Question 3

how is ßthalassaemia inherited?

Answer 3

autosomal recessive

Question 4

what would laboratory test show in the presence of ßthalassaemia?

Answer 4

FBC: hypochromic microcytic indices - increased RBCs relative to Hb

Film: target cells, poikilocytosis but no anisocytosis

Hb EPS/HPLC: ßthal - raised HbA2 + HbF

DNA studies: genetic analysis for mutations & Xmnl polymorphism

Question 5

thalassaemia major:

Answer 5

homozygous, severe anaemia, incompatible with life without regular blood transfusions, clinical presentation usually >4-6 months old

Question 6

how does thalassaemia major present?

Answer 6

severe anaemia, hepatosplenomegaly, blood film showing hypochromia & poikilocytosis & many NRBCs, erythroid hyperplasia in bone marrow, extra-medullary haematopoeisis

Question 7

what are the clinical features of ßthalassaemia?

Answer 7

chronic fatigue, failure to thrive, jaundice, delay in growth + puberty, skeletal deformity, splenomegaly, iron overload

Question 8

what are the complications of ßthalassaemia?

Answer 8

cholelithiasis (gallstones) & biliary sepsis, cardiac failure, endocrinopathies, liver failure

Question 9

what is the major cause of death from ßthalassaemia?

Answer 9

cardiac failure (due to iron overload)

Question 10

how can ßthalassaemia be managed?

Answer 10

regular blood transfusions, iron chelation therapy, splenectomy, supportive medical care, hormone therapy, hyrdroxyurea (to boost HbF), bone marrow transplant, management of infection (especially in splenectomised patients)

Question 11

transfusions:

Answer 11

phenotyped red cells, pre-transfusion Hb should be 95-100g/L, regular transfusions (2-4 weekly), if high requirement consider splenectomy

Question 12

iron chelation therapy:

Answer 12

12 hours subcutaneous administration, starts after 10-12 transfusions / when serum ferritin >1000mcg/l, audiology & opthalmology screening prior to start

Question 13

what are the different iron chelation drugs and what are their side effects?

Answer 13

• deferasirox (oral): rash, GI symptoms, hepatitis, renal toxicity
• desferrioxamine (SC infusion 8-12 hours 5-7days a week): vertebral dysplasia, pseudo-rickets, retinopathy, high tone hearing loss
• deferiprone (oral): arthropathy, neutropenia & agranulocytosis (-> susceptible to infection)
• combination therapy: any 2 aforementioned drugs, allows toxicity control

Question 14

how can you monitor iron overload?

Answer 14

serum ferritin (>2500 associated with complications but doesn’t correlate well to tissue iron levels), liver biopsy (but risky & inaccurate as levels vary within liver), T2 cardiac and hepatic R2 MRI