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before resort to further investigation. It is worth noting that the commonest form of
anaemia worldwide is that caused by iron deficiency. With the notable exception of
acute blood loss, reduction in red cell mass is accompanied by an increase in
plasma volume, thus pre- serving blood volume. The mechanism for this is not clear
but it is one of the compensatory mechanisms adopted during anaemia of any
duration. Of equal importance is a shift of the oxygen dissocia- tion curve to the
right through increased synthesis of 2,3-diphos- phoglycerate (2,3-DPG) in the red
cell via the Embden-Meyerhof pathway of anaerobic glycolysis and the RapaportLuebering shunt. Increases in 2,3-DPG render the haemoglobin molecule less avid
for oxygen at any given partial pressure and improve tissue oxygenation. Two
remaining compensatory mechanisms in anaemia are an increase in cardiac stroke
volume and an increase in heart rate. In acute blood loss, red cells and plasma are
lost together, such that in the first few hours haemoglobin and haematocrit
measure- ments change little and cannot be used to estimate blood loss. Surgeons
have always attributed much importance to the haemat- ocrit, but in continued
acute bleeding the haemoglobin and haematocrit move in parallel. Haemodilution is
complete by 24-48 h if transfusion of red cells is not carried out.
GENETIC ABNORMALITIES OF
HAEMOGLOBIN
The inherited abnormalities of haemoglobin include a complex and diverse series of
genetic defects resulting from impaired pro- duction of normal globin chains
(thalassaemias) or synthesis of an abnormal haemoglobin. The thalassaemias are
characterized by absent or reduced production of the affected globin chain whilst
the other chains which make up the haemoglobin molecule are structurally normal.
In the haemoglobinopathies, the affected
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23 HAEMATOLOGY
chain, usually the |3 or a chain, has an amino acid substitution which, if it affects
the structure or function of the haemoglobin molecule as a whole, may produce
clinical effects.
(3-THALASSAEMIA
(3-Thalassaemia, in which (3-globin chain synthesis is impaired, is classified into
three clinical grades. fi-Thalassaemia ra*(thalassaemia minor) is the
heterozygous state and produces little clinical effect. There may be slight anaemia
and the condition may be mistaken for iron deficiency. In pregnancy, the
haemoglobin may decrease below the reference range. Thalassaemia intermedia, as
the name implies, is associated with more marked anaemia than thalassaemia trait
and is generally caused by double heterozygosity or homozygosity of less severe (3-
thalassaemia genes. Occasionally, patients may require transfu- sions of red cells.
Thalassaemia major (Cooley's anaemia) is the homozygous inheritance of severe (3thalassaemia genes; (3-chain production is reduced ((3+) or absent ((3), thus
impairing the synthesis of adult haemoglobin. Without blood transfusion the
condition is gener- ally fatal in the early years of childhood, and even with regular
transfusion support, patients may not live beyond their early 20s as a result of iron
overload. Long-term iron chelation therapy may prevent transfusional iron overload
and bone marrow transplanta- tion may be considered.
a-THALASSAEMIA
a-Thalassaemia is a genetically variegate disorder which ranges in severity from
fetal death in utero in the homozygous form to a mild hypochromic disorder in the
heterozygous form. Patients with three of the four a-chain genes deleted suffer HbH
disease of intermediate severity and some require transfusion with red cells.
SICKLE CELL DISEASE
More than 100 haemoglobin variants have been described, but only one has
significant global clinical impact - haemoglobin S. Ten per cent of patients of African
extraction carry the S gene. It is also seen in Italy, Greece, Arabia and the Indian
subconti- nent. Haemoglobin S has valine substituted for glutamine in position 6 of
the p-globin chain and this confers physical differ- ences on the haemoglobin
molecule with profound clinical con- sequences in homozygotes. Haemoglobin S
becomes insoluble at oxygen tensions in the venous range (5-5.5 kPa) and crystallizes, imposing a sickle cell shape on the red cell. The sickled red cell is rigid and
does not pass easily through capillaries, leading to occlusion, tissue infarction and
the pain which is characteristic of clinical episodes known as crises. Red cell survival is reduced greatly and homozygous patients invariably have anaemia (6-10 g
dh1) and jaundice. Heterozygotes are mostly asymptomatic but their red cells may
sickle when oxygen tensions are unphysiologically low. Haemoglobin S may exist in
combination with other genetic defects of haemoglobin, the most significant
combinations being HbS/f3-thalassaemia and HbSC disease. Symptoms may be
similar to those of homozy- gous HbSS although HbSC has a particular tendency to
throm- bosis and retinopathies.
Patients with haemoglobinopathies are at risk of unique peri- operative
complications and increased mortality. Haemoglobin electrophoresis should
therefore be performed in all patients of affected ethnic groups to establish the
presence or absence of haemoglobin S before anaesthesia. In an emergency, sickle
haemoglobin may be demonstrated rapidly in patients' blood using a commercial
kit, e.g. Sickledex (Ortho Diagnostics). It may be necessary to pre-transfuse
homozygotes electively or consider exchange transfusion to raise the percentage of
haemo- globin A compared with haemoglobin S, particularly for surgery involving
cardiopulmonary bypass. In all cases, it is essential to maintain good oxygenation