by Dr. Adele Visser

Introduction

Haemoglobin is the major oxygen-carrying molecule within red blood cells and consists of a heme component (iron containing) and globin chains (proteins). Within the class of haemoglobinopathies, the fundamental problem lies with these globin chains, either in their structure (qualitative) or amount (quantitative) produced. This may lead to haemolytic anaemias, thalassaemias, familial polycythaemias or methaemoglobinemia.

Quantitative abnormalities in globin production

Normal adults contain three different types of haemoglobin (table 1), which is made up of two alpha chains and two other globin chains, depending on the subtype. HbA is the dominant type found in normal adults and is made up of two alpha chains and two beta chains.
Table 1. Various types of haemoglobin found within a normal adult patient.

 

 

Thalassaemia is defined as and alpha-thalassaemia where disproportionately less alpha chain is produced in relation to beta chain and beta-thalassaemia the disproportionate reduced production of beta chains in relation to alpha chains.

Alpha chain production is encoded for on chromosome 16 where 2 copies per chromosome (therefore 4 genes) of the gene is found. Disease severity is determined by the amount of gene copies that are deleted or dysfunctional. The alpha chain is essential in fetal life as it is an irreplaceable part of all fetal types of haemoglobin. If all four genes are deleted, the patient will present in utero with hydrop foetalis (figure 1)

The use of hs-cTn assays have been of interest as a marker for cardiovascular risk stratification in the general population. Despite its promise, studies are lack running both assays head-to-head, making comparison difficult owing to cohort differences. Comparison of data from studies run separately, demonstrate a slightly higher hazard ratio for future CVD events⁹ as well as non-CVD death¹⁰ using hs-cTnT over hs-cTnI. Of note, hs-cTnI show a greater predictive correlation in combination with age, male sex, body mass index and systolic pressure, whereas hs-cTnT shows greater predictive     correlation in combination with diabetes¹¹.

Laboratory diagnosis

Thalassaemia presents hypochromic, microcytic anaemia of varying severity. The reticulocyte count is increased. Although not typical of iron deficiency, it is still advocated to perform iron studies as a first line investigation. If deficient, supplementation is advocated prior to further testing. If the red cell morphology persists, an Hb electrophoresis is indicated. In the case of beta-thalassaemia, a marked increase in HbF will be noted with the virtual absence of HbA. Iron management will be essential in these patients as the ineffective erythropoiesis prompts a marked increase in iron absorption. Therefore, despite the microcytosis, these patients should never be supplemented with iron.
Alpha thalassaemia may also present with red cell morphological abnormalities. Definitive diagnosis requires DNA analysis as Hb electrophoresis is typically normal. In addition, the degree of ineffective erythropoiesis is much less pronounced and the clinical implication of this diagnosis is therefore less impactful for the patient.

References

Hoffbrand AV, Moss PAH, Pettit JE. 2007. Essential Haematology. 5th edition.