The aims of treatment in the beta-thalassaemias are:
- correct anaemia with regular blood transfusions
- suppress ineffective erythropoiesis and therefore bony deformity
- carry out effective genetic counselling
Patients with thalassaemia major should be transfused as often as necessary to maintain a Hb of greater than 9.5 - 10.0 g/dl (1)
- this may mean transfusion every 4 to 6 weeks (1). Clearly with this degree of transfusion one must use leucocyte depleted blood to prevent febrile transfusion reactions and iron chelation therapy to prevent iron overload.
- red cell units which are matched for Rh (D, C, c, E, e) and Kell (K) blood group reduce the risk of serious transfusion reactions. (1)
Transfusions must be started when there are clinical evidence of severe anaemia (~ 7 g/dl), failure to thrive, and/or thalassaemic bone deformity (1).
The biggest problem with regular transfusions is iron overload.
- with regular transfusions the patient will accumulate 0.3-0.5mg/kg of iron per day which is toxic especially to the heart, liver and endocrine glands.
- iron overload must be monitored and children should have access to MRI modalities (Cardiac T2* MRI and either R2 or T2* of liver) to monitor Cardiac and liver iron overload. (1) If not will lead to heart failure by the age of 20.
- at present iron chelation is with overnight (8-12 hours) subcutaneous infusions of desferrioxamine 5-7 nights per week.(1)
- one may consider the oral iron chelator deferiprone (1)
- it is important to monitor patients on a regular basis for iron overload by measurement of serum ferritin.
Regular ocular examination is also necessary since desferrioxamine therapy can cause cataracts. Iron excretion induced by desferrioxamine is enhanced by concomitant administration of vitamin C.
If transfusion requirements are unreasonable splenectomy is indicated (1). Transfusion requirements can be reduced significantly following splenectomy. (1)
Alternatives to the conventional treatment described include bone marrow transplant (1) and the use of agents to augment the production of fetal haemoglobin.
With modern treatment patients with thalassaemia major usually survive to adult life.
Gene Therapy in beta thalassaemia (2):
- involves the insertion of a vector containing the normal beta-globin or gamma-globin gene into haematopoietic stem cells to permanently produce normal red blood cells
- gene editing and base editing involves the use of zinc finger nucleases, transcription activator-like nucleases and clustered regularly interspaced short palindromic repeats/Cas9 to either correct the causative mutation or else insert a single nucleotide variant that will increase foetal haemoglobin
Notes:
- management (Thalassaemia intermedia)
- these patients should be recognized and blood transfusions should not be used inappropriately (1)
- close monitoring especially in the first 3-5 years is needed to identify thalassaemic features which may require regular transfusion therapy (1)
- acute aneamia associated with infection or G6PD-deficiency can occur requiring transfusion but regular transfusions are not generally needed (1)
- iron chelation maybe needed but regimes are less intense (1)
- folic acid supplementation maybe needed as there is a relative folate deficiency (1)
- patients with massive splenomegaly and hypersplenism are candidates for splenectomy (1)
- masses causing compression of spinal cord or roots or causing pressure symptoms may require surgical treatment (1).
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