1.Reduced rate of production of one or more of the globin chains QUANTITATIVE Thalassaemias2. Structural change in a globin chain leading to instability or abnormal oxygen transport QUALITATIVE
Major - The severe transfusion-dependent Minor - The symptomless carrier states Intermedia - A group of conditions of intermediate severity This classification is retained because it has implications for both diagnosis and management
Thalassemia major ◦ Requiring more than eight red blood cell transfusions per year Thalassemia intermedia ◦ No or infrequent transfusions Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of beta-thalassemia major in North America. Blood 2004;104(1):34– 9.
According to which globin chain is produced in reduced amounts ◦ α, β, δβ or εγδβ thalassemias α0 or β0 thalassemias ◦ No globin chain is synthesized at all α+ or β + thalassemias ◦ Some globin chain is produced but at a reduced rate
• Reduced rate of production of one or more of the globin chains• Imbalanced globin chain synthesis
HbF level ◦ Always elevated ◦ Heterogeneously distributed among the red cells. β0-thalassaemia ◦ No HbA, β+-thalassaemia ◦ Level of HbF ranges from 30% to 90%. HbA2 level ◦ Of no diagnostic value
MICROCYTHEMIA ◦ Increased number of red cells which are smaller than normal POIKILOCYTOSIS ◦ Abnormally shaped cells Target cells Irregularly distorted cells Punctate basophilia (basophilic stippling of red cells)
HbE β-thalassaemia The commonest severe form of thalassaemia in South-East Asia and parts of the Indian subcontinent. There is usually severe anaemia and splenomegaly with typical thalassaemic bone changes Diagnosis is confirmed by ◦ Only HbE and HbF on haemoglobin electrophoresis ◦ HbE trait in one parent and the β-thalassaemia trait in the other
Widening of thecalvarium"hair-on-end"appearance.
1. Carrier detection and genetic counselling about the choice of marriage partners ◦ If two β-thalassemia heterozygotes marry, ??2. Prenatal counselling ◦ when heterozygous mothers are identified prenatally, the husbands may be tested If both are carriers, ??
Should be offered only to couples at risk for having children with severe disease ◦ Studies of globin chain synthesis in fetal blood samples obtained by fetoscopy at 18–20 weeks’ gestation ◦ Analysis of fetal DNA obtained by CVS between weeks 9 and 12 of gestation Southern blot PCR
Young BRC’s Extension of transfusion interval Cost vs. Benefit• Neocytes have had a minor impacton the long-term management
If possible, patients with thalassemia should receive blood matched for ◦ ABO ◦ CcDdEe, and ◦ Kell antigens
In the past ◦ When annual transfusion requirements exceed 200–250 mL packed cells per kilogram body weight, splenectomy significantly reduces these requirements In the modern era ◦ With improved transfusion practices Hypersplenism is reduced Many patients do not require splenectomy.
Prolonged parenteral infusion using portable ambulatory pumps
Erratic compliance, especially in adolescents
Successful cure of b-thalassemia by bone marrow transplantation first was reported by Thomas and associates in 1982. Thomas ED, Buckner CD, Sanders JE, et al. Marrow transplantation for thalassaemia. Lancet 1982;2(8292):227–9.
The combination of ◦ Early diagnosis ◦ Improvements in monitoring for organ complications, and ◦ Advances in supportive care many patients who have severe thalassemia syndromes to live productive, active lives well into adulthood