A 3-year-old child from Southeast Asia presents with pallor and fatigue at the paediatric casualty department. She is said to have a history of alpha thalassaemia, namely haemoglobin H disease (HbH).

A full blood count is performed with the following results:

Hb 78 g/L, MCV 75.3 fL, MCH 20.8 pg, Platelet count 358 x 10⁹/L

A blood film is examined with the following morphology:

Anisocytosis, microcytes, hypochromasia, elliptocytes, polychromasia, target cells and coarse basophilic stippling.

Morphologically the blood film is not suggestive of HbH disease. Coarse basophilic stippling is not a feature of HbH disease. Also the MCV and MCH are higher than that seen in HbH disease.

Alpha thalassaemias are caused by a decrease in the production of alpha globin genes. This decrease in alpha genes is due to a deletion or mutation of one or more of the four alpha Aglobin genes located on chromosome 16.

The alpha thalassaemias are divided into four groups:

One gene deletion – silent trait
Two gene deletion – thalassaemia trait
Three gene deletion – HbH disease
Four gene deletion – hydrops foetalis

The silent carriers have no clinical abnormalities. The haemoglobin level is within the normal range while the MCV is borderline normal. Those with alpha thalassaemia trait are clinically normal however the haemoglobin is low while the indicies are microcytic and hypochromic. The average MCV is 68 fL and the average MCH is

21 pg. Those with HbH disease are also clinically normal however their haemoglobin level is moderately low. The average MCV is 57 fL and the average MCH is 21 pg. Those with hydrops foetalis fail to produce alpha globin chains. They have four gamma chains or haemoglobin Barts. Also they are delivered stillborn, usually at 30 to 40 weeks.

Haemoglobin H disease can be associated with a rare haemoglobin known as Haemoglobin Constant Spring (HbCS). HbCS is an alpha chain variant rather than a deletion. The alpha chain is elongated by 31 additional amino acid residues at the C-terminal end, making it very unstable. The presence of HbCS causes the red cells to break down faster than usual giving rise to a severe anaemia.

The red cells of HbCS are large and different from those seen in any of the other forms of thalassaemia. The cells are markedly overhydrated relative to those of the deletional forms of alpha thalassaemia. This phenomenon is expressed early in erythroid maturation and is fully expressed at the reticulocyte stage.

As the MCV and MCH of our patient did not support a clinical diagnosis of HbH disease alone, it was decided to perform a haemoglobin EPG. The results are as follows:

Haemoglobin H inclusions detected.
Abnormal bands of HbH, Hb Barts and Hb Constant Spring detected.

A diagnosis of HbH-CS was confirmed on this patient.

Clinically, HbH-CS is more severe than HbH disease. Patients with HbH-CS have a moderate to severe anaemia and ultimately develop complications such as an enlarged spleen. Some need blood transfusions from time to time, especially when they develop a fever for example, while others need to be transfused more frequently.