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CHAPTER 7

Haemoglobinopathies

G. Olufemi Ogunrinde G. Ifeyinwa Onimoe
Rebecca Inglis Richard Onalo

Introduction As a result of the abnormal globin protein, both the haemoglobin
Children with haemoglobin disorders are more likely than the general molecules and the erythrocytes that contain them are unstable and
population to need to undergo surgery during their lifetimes to treat the can break down under predisposing conditions (hypoxia, acidosis,
common surgical manifestations of their condition. However, they are also hypertonicity), releasing free haemoglobin radicals that lead to oxidative
more likely to experience complications as a result of that surgery, with stress on the vascular endothelium. This sets up a chronic inflammatory
complication rates as high as 32% in patients with sickle haemoglobinopa- process in the vasculature of patients with SCD, and this is thought to be
thies. Careful peri- and postoperative management is required to minimise the starting point for many of the pathological processes observed. The
the risk of complications. Furthermore, the prevalence of haemoglobin- abnormal globin chain also causes the red cells to become less deformable
opathies, with an estimated 269 million carriers worldwide, means that the and to stick more readily to the vascular endothelium. The downstream
possibility of an undiagnosed haemoglobin disorder should be considered result is vaso-occlusion, leading to pain, ischaemia, and infarction, which
prior to undertaking a surgical procedure in any child. can occur anywhere in the body, including the bones, abdominal viscera,
Demographics and penile vasculature. Accelerated haemoglobin breakdown also leads
to chronic haemolysis and a persistent state of anaemia.
The haemoglobinopathies are the most common genetic disorders Chronic haemolysis is also a central feature of the thalassaemias,
worldwide. One in 20 people are carriers of a defective haemoglobin and the major clinical manifestations of these conditions relate to
gene, and 300,000 babies are born each year with a major haemoglobin variably severe anaemia. Other complications occur due to iron
disorder. Africa is disproportionately affected, shouldering two-thirds overload with end organ damage due to iron deposition.
of the disease burden, with sickle cell disease particularly prevalent. The laboratory tests required to make a diagnosis of a haemoglobinopathy
The distribution of sickle cell disease across the continent is are described in Table 7.1. An important part of the diagnostic process is
influenced by the resistance to severe malaria conferred by carrying a having a high index of suspicion in at-risk populations. The possibility of
single copy of the sickle cell gene. Even though malaria resistance does an undiagnosed haemoglobinopathy should be actively considered in any
not extend to those affected by homozygous sickle cell disease itself, the child who could potentially require surgery.
survival advantage for carriers means that the sickle cell trait is selected
for in areas where malaria is endemic. As a result, sickle cell disease Table 7.1: Laboratory Investigations for the haemoglobinopathies.
is more prevalent in sub-Saharan Africa, particularly those countries Investigation Typical finding
bordering the equator. Sickle cell disease is an especially significant
problem in Nigeria, where 24% of the population are carriers and the Full blood count Normocytic anaemia (SCD)
Microcytic anaemia* (thalassemia/HbSC)
condition affects 2 in every 100 live births. This means that in Nigeria
alone, 150,000 children are born with sickle cell anaemia each year. May show sickled erythrocytes, target cells, and nucleated
Blood film red cells in sickle cell disease. Basophillic stippling is a
Aetiology/Pathophysiology nonspecific finding in some thalassaemias.
Haemoglobinopathies are disorders that affect the globin part of the hae- Demonstrates a single band of HbS in sickle cell anaemia
moglobin molecule. Genetic defects can lead to either decreased globin Haemoglobin or HbS with another mutant haemoglobin in compound
synthesis, producing the thalassaemia syndromes, or abnormal globin electrophoresis heterozygotes. A raised level of HbA2 is consistent with
β-thalassaemia.
structure, resulting in disorders that include sickle cell disease (SCD).
The haemoglobin molecule comprises four globin chains (two Red cell staining Reveals aggregates of β globin protein in α-thalassaemia
alpha and two beta chains), which are genetically coded: different A number of rapid screening tests are available for the
types combine to make different subtypes of haemoglobin. Of note, Sickle solubility detection of sickle haemoglobin. Although helpful in some
two distinct globin chains (each with its individual haem molecule) and instability settings, their use is not appropriate for definitive diagnosis
tests
combine to form a haemoglobin. because they miss other variants
Sickle cell disease is caused by an abnormal beta chain due to an Often not required, but may be helpful in ascertaining diag-
amino acid substitution, valine for glutamic acid at β6. Other structural DNA analysis nosis of thalassaemias.
qualitative haemoglobinopathies include haemoglobin C (glutamic
acid to lysine at β6) and haemoglobin E (lysine for glutamic acid * Iron studies should be sent to exclude iron deficiency.
at β 26). Sickle cell disease comprises a group of clinical disorders,
which includes homozygous sickle cell anaemia (HbSS), sickle cell Surgical Manifestations of Sickle Cell Disease
haemoglobin C disease (HbSC), sickle cell thalassaemia disease Acute Abdominal Pain
(HbS/β thal) and other compound heterozygous conditions. The carrier
state, sickle cell trait HbAS, is not usually associated with increased Acute abdominal pain in children with sickle cell disease presents
morbidity or mortality. a significant diagnostic challenge. Painful vaso-occlusive crises can
mimic surgical pathologies and are difficult to differentiate on clinical