1. Reduced rate of production of one or more of the globin chains

QUANTITATIVE

Thalassaemias

2. Structural change in a globin chain leading to instability or abnormal oxygen transport

QUALITATIVE

Thalassaemias

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

Clinical Classification

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

Genetic Classification

Alpha

Beta

Β Thalassaemia

•Reduced rate of production of one or more of the globin chains

•Imbalanced globin chain synthesis

Thalassemia

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

Hemoglobin Changes

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)

FBC Changes

Serum ferritin – Increased % Saturation - Increased

IRON STUDIES

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

b-Thalassaemia in association withhaemoglobin variants

Widening of the calvarium "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, ??

Prevention and Treatment

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

Prenatal Diagnosis

Leukocyte-reduced red cell

Young BRC’s Extension of transfusion interval

Cost vs. Benefit

Neocytes

• Neocytes have had a minor impact on the long-term management

If possible, patients with thalassemia should receive blood matched for ◦ ABO◦ CcDdEe, and ◦ Kell antigens

Alloimmunization

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.

Splenectomy

Infectious complications

Prolonged parenteral infusion using portable ambulatory pumps

Deferoxamine

Erratic compliance, especially in adolescents

Difficulty associated with long-term sc deferoxamine therapy

Orally active iron chelating agents

Long-term Monitoring

Successful cure of b-thalassemia by bone marrow transplantation first was reported by Thomas and associates in 1982.

BMT

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