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In the more easily identifiable forms of thalassaemia heterozygosity, the haemoglobin level is reduced while the number of the circulating red blood cells (RBCs) is superior to the norm. The Hb deficiency causes leptocytic RBCs manifesting a greater resistance to the haemolysis in salty hypotonic solutions.

Complementary examination is the morphological study of RBCs which reveals different characteristics between the normal subjects and thalassaemia carriers and a series of morphological alterations: hypochomic erythrocytes, presence of erythrocytes with different form and measure, target erythrocytes.

I globuli rossi nella microcitemia

The haemochromocytometric exam shows the presence some characteristics that can make to suspect the presence of a thalassaemia heterozygosity.

Schema delle caratteristiche in un soggetto normale e uno microcitemico

All these characteristics allow hypothesizing the presence in a subject of evident forms of thalassaemia heterozygosity.

As regard the lightest forms and the double β + α associations the haematological characteristics are very attenuated and cause a difficult identification.

Diagnostic exams for β thalassaemia heterozygosity

  • the haemochromocytometric and morphological exam of blood;
  • study of the osmotic globular resistance;
  • sideremia and ferritin dosage;
  • electrophoretic and/or chromatographic study of the haemoglobins.

These haematological analyses are fundamental to diagnose above all the β thalassaemia carriers and those with abnormal haemoglobins. In fact, a lot of thalassaemias of the non-α group are characterized by specific alterations of the haemoglobin picture.

In the β thalassaemia the HbA2 level is average the double of the normal one (5% or more, rather than 2,5%).

The thalassaemia heterozygosity with Hb Lepore is characterized by 8-10% of haemoglobin that in electrophoresis at alkaline pH shows inferior mobility to that of the HbA; and by a normal level of HbA2.

The F thalassaemia (or δβ thalassaemia) is manifest with 10-15% of Hb F and with a normal HbA2.

Diagnostic exams for α thalassaemia

In order to suspect the diagnosis of α thalassaemia, as first approach, the analyses performed for the β thalassaemia diagnosis are usually sufficient.

However the α thalassemia carriers are haemaglobinically healthy therefore not having an increased HbA2 level.

The most marked α forms can be suspected thanks to the presence of haematological alterations similar to β ones: increased number of the circulating RBCs, reduced osmotic globular resistance, reduction of the hemoglobin value, alterated erythrocytic morphology.

The haematological picture of the α thalassaemias is often similar to the Fe++ deficiencies.

More sophisticated tests (exams of second level) are necessary to confirm the diagnosis in subjects with haematological alterations and a normal haemoglobin picture.

Diagnostic exams: second level

  • globin chain synthesis' study in vitro
  • family analysis

A particular technique (the in vitro globin synthesis) allows calculating the degree of α globin chain synthesis reduction in comparison to the β chains. In the normal subject the α/β ratio is around 1 (indicating that the same number of α and β chains are produced). In the α thalassaemia carrier it is instead characteristic a reduced globin chain synthesis and therefore the ratio is about <1.

The family exam (i. e. parents or brothers and sisters) is often conclusive to support the diagnosis of particular cases with more associations of various thalassaemia forms in the same subject.

Diagnostic exams: third level

  • DNA study of the globin genes.

In some situations, the preceding methods are not adequate, and further testing, third phase, must be performed to reach a final diagnosis.

The DNA study is also essential in the subjects that belong to a couple at risk for having children affected by Mediterranean anaemia, in order to be able to perform prenatal diagnosis at the righ moment.