Hemoglobinopathies (Part Two)

α -Thalassemia Minor (carrier of α -Thalassemia, α-Thalassemia trait)

When one or two alpha genes are missing, it is referred to as α-Thalassemia trait. A characteristic is the increased number of erythrocytes, hemoglobin at normal or slightly decreased levels, MCV and MCH are low (erythrocyte constants of size and hemoglobin content). Hemoglobin Electrophoresis is normal. The diagnosis is easy in newborns because MCV is low and an increased amount of HbBart can be detected. After this period, the diagnosis is difficult.

The disease is suspected from erythrocytosis, normal hemoglobin (a mismatch of erythrocyte count with the hemoglobin value according to the rule of 3 for normochromic, normocytic erythrocytes), reduction in MCV and MCH, in the absence of iron deficiency and electrophoretic changes. Morphological changes in erythrocytes are less pronounced than in β-Thalassemia and basophilic granulations are rarely seen. There is resistance to iron treatment. Confirmation of the diagnosis is made by studying both parents if possible for changes or by detecting HbH inclusions in peripheral blood erythrocytes stained with Brilliant Cresyl Blue (reticulocyte).

To establish an accurate diagnosis, which is not done in our country, it is necessary to evaluate the α/β ratio (in reticulocytes) of protein chains, which normally is 1:1 and in alpha-Thalassemias is decreased, while in beta-Thalassemias is increased. DNA analysis is also performed.

β-Thalassemia minor (carrier of β -Thalassemia, β-Thalassemia Trait)

Generally discovered incidentally, during an examination or screening. It is characterized by changes in peripheral blood; mild hypochromic microcytic anemia, Hb 9-12 gr/dl, higher number of erythrocytes than normal, MCV and MCH are low, HbA2 (in Hb electrophoresis) is increased above 3.5% (3.5-8%). HbF is normal or slightly increased.

Caution borderline HbA2 values = 3.5 % (Hemoglobin Electrophoresis should be evaluated by a specialist, it does not have the accuracy of genetic analysis, errors are possible).

Clinically it is asymptomatic or with very mild signs. There may be mild pallor, subicterus or jaundice (yellowing) of the skin and sclerae, splenomegaly, radiographic changes in long bones. The number of reticulocytes and the value of indirect bilirubin may be slightly increased. Iron (ferritinemia) in the body is at normal or increased levels. It is often confused with iron deficiency anemia and treated mistakenly with iron. Iron absorption is increased compared to normal individuals and in some cases can cause hemosiderosis clinic.

In contrast to the mild degree of anemia, morphological alterations in the red series are pronounced. These include microcytosis, hypochromia, poikilocytosis (target cells, leptocytes, basophilic granulations). The CBC is normal or with a slight hyperplasia of the erythroid series. No inclusions of α chains, precipitated in the precursors of the red series with methyl violet staining, are found. Erythrokinetic studies show slightly shortened lifespan of erythrocytes and modest ineffective erythropoiesis.

Children who will develop thalassemia minor are normal at birth and starting from the age of 4 – 6 months the values of hemoglobin, MCV, MCH, HbA2, and HbF fall outside the normal values. The drop in HbF after birth is delayed and the increase in HbA2 is accelerated.

Since the synthesis of hemoglobin requires iron and Folic Acid, their deficiency can cause low levels of hemoglobin (and consequently HbA2) and higher levels of HbA2 cannot be found until the respective deficiency is corrected. When Thalassemia Minor is suspected, initially iron Deficiency Anemia should be corrected if confirmed (Ferritinemia is key) and Anemia from Folic Acid Deficiency (respective deficiencies only without anemia, is not a problem) to eliminate any overlaid anemia and remain only with the congenital anemia.

In β-thalassemia, only HbA will be affected (decreased) (as a result of the absence of β chains), whereas HbA2 will be increased compensatorily (to compensate for the excess α chains that will bind with δ) and similarly, HbF will be increased compensatorily (to compensate for the excess α chains that will bind with γ).

A practical rule (The Mentzer index); the ratio between MCV and the number of Erythrocytes (RBC). If this ratio is < 13 it speaks for Thalassemia Minor and when it is > 13 it speaks for Iron Deficiency Anemia.

Patients with Thalassemia Minor can donate blood (if blood parameters and age allow). And they have donated because many of them do not know. In Albania, their erythrocytes (with a shorter lifespan than normal erythrocytes) are usually given to a normal person and not one with Hb-pathies.

• Iron deficiency; MCV decreased and RDW increased.
• β-thalassemia minor; MCV decreased and RDW normal.

Hemoglobin Fractions in Genotypic Variants of beta-Thalassemia Minor.