The
haemolytic anaemias
There are five causes of haemolytic anaemia
which are amenable to splenectomy:
•
hereditary spherocytosis;
• acquired autoimmune haemolytic anaemia;
• thalassaemia;
• hereditary
ëlliptocytosis;
• pyruvate kinase deficiency.
Hereditary
spherocytosis
The essential lesion is an increase in
permeability of the red cell membrane to sodium. As the sodium leaks into the
red cell its osmotic pressure rises, it swells and becomes more spherical, and
in consequence more fragile. The mechanism by which the cells rids itself of
sodium — the
sodium pump —has
to work harder. This has two consequences: (1) there is greater loss of membrane
phospholipid and so a weakening of the membrane which thus becomes more fragile;
and (2) the energy and the oxygen requirements increase. These requirements are
particularly difficult to satisfy in the spleen where there is deficiency of
both glucose and oxygen. Thus, a large number of red cells is destroyed in the
spleen, and splenectomy reduces this cell destruction. Splenectomy does not, of
course, cure the congenital red cell membrane defect, but it lessens the anaemia
and makes the red cell survival time normal. The defect is transmitted by either
parent as a Mendelian autosomal dominant (in 1866 Mendel described
‘dominant’ and ‘recessive’ traits in hybrids; his work passed unnoticed
for 35 years). Males and females are equally affected. The
circulating bilirubin is not conjugated with glucoronic acid. It is attached to
albumin and is not excreted in the urine (acholuric jaundice). Although there is
excessive breakdown of red cells with transformation of liberated haemoglobin to
bilirubin, the bilirubin compound so produced is excreted by the liver and not
the kidneys, thus favouring the formation of pigment gallstones.
Clinical
features
Once the disease manifests itself, spontaneous
remissions are almost unknown. As a rule the patient is pale and has jaundice.
In established cases lassitude and undue fatigue are present, but they vary with
the degree of haemolysis.
Sometimes
the patient is born jaundiced or becomes so early in life. In certain families
the disease is characterised by severe crises of red blood cell destruction;
thus, with the onset of a crisis, an erythrocyte count may fall from 4.5 x 106
to 1.5 x 106 in less than a week. Such crises are characterised by the onset of
pyrexia, abdominal pain, nausea, vomiting and extreme pallor, followed by
increased jaundice. These crises may be precipitated by acute infection, and can
be so severe as to cause death in infancy or childhood. More usually the
jaundice, although variable, is very mild and may not appear until adolescence
or even adult life. In adult cases there is often a history of attacks of
biliary colic; indeed, 68 per cent of untreated patients over the age of 10
years have pigment stones in their gall bladder. Every child with gallstones
should be investigated for hereditary spherocytosis, and enquiry should be made
among relatives of patients with spherocytosis for evidence of similar disease.
On
examination the
spleen is large and, in thin patients, can be palpated easily. Sometimes the
liver is also palpable. Chronic leg ulcers can occur in adults with the disease.
Haematological
investigations
The fragility test. Increased fragility of
erythrocytes characterises this disease. Normally, erythrocytes begin to
haemolyse
in 0.47 per cent saline solution. In this condition haemolysis occurs in 0.6 per
cent or in even stronger solutions.
The
reticulocyte count. To compensate for the loss of erythrocytes by
haemolysis, the bone marrow discharges into the circulation immature red cells
which differ from adult cells by possessing a reticulum.
Faecal
urobilinogen. Faecal urobilinogen is increased, as most of the urobilinogen is
excreted by this route.
Use
of radioactive chromium. Labelling the patient’s own red cells with
51Cr
will
demonstrate the severity of red cell destruction, and if this is accompanied by
daily scanning over the spleen it will show the degree of red cell sequestration
by the spleen. If splenic radioactivity is high, splenectomy will be of value.
Treatment
All patients who have hereditary spherocytosis
should be treated by splenectomy. In juvenile cases the age at which
Acquired
autoimmune haemolytic anaemia
This may be due to a drug reaction (e.g. to
alpha-methyldopa), to another disease (e.g. systemic lupus erythematosus) or its
cause may be unknown. Red cell survival is reduced because of an immune reaction
triggered by immunoglobulins or complement on the red cell surface. The red cell
surface is damaged as a result of the binding of the Fc portion of the red cell
antibody to a macrophage Fc receptor in the spleen. The red cell is thus
rendered vulnerable to ‘culling’ within the red cell pulp.
Clinical
features
Autoimmune haemolytic anaemias are more common
after the age of 50 years and in women. The spleen is enlarged in 50 per
cent and pigment gallstones are present in 20 per cent of cases.
Investigations
Anaemia is invariably present and may be
associated with spherocytosis because of red cell membrane damage. The Coombs’
test is usually, but not invariably, positive.
Treatment
Usually the disease has an acute, self-limiting
course, and no treatment is necessary. Splenectomy should, however, be
considered if:
•
corticosteroids are ineffective;
•
the patient is developing complications from long-term steroid treatment;
•
corticosteroids are contraindicated, for example because of a history of
peptic ulcer.
Eighty per cent of patients respond to
splenectomy.
Thalassaemia
(syn. Cooley’s anaemia; Mediterranean anaemia)
Thalassaemia is the result of a defect in
haemoglobin peptide chain synthesis which is transmitted as a dominant trait.
The disease is really a group of related diseases alpha beta and
gama, depending on the
haemoglobin peptide chain whose rate of
synthesis is reduced. Most patients suffer from
beta-thalassaemia in which a reduction in the rate of beta-chain synthesis results in
a decrease in haemoglobin A. In addition to a decrease in haemoglobin,
intracellular precipitates (Heinz bodies) contribute to premature red cell
destruction. The disease is no longer thought to be confined to those living
around the Mediterranean.
Clinical
features
Graduations of the disease range from
heterozygous thalassaemia minor to homozygous thalassaemia major which is
associated with chronic anaemia, jaundice and splenomegaly. Patients with
homozygous thalassaemia major frequently develop clinical signs within the first
year of life: retarded growth, enlarged head with slanting eyes and depressed
nose, leg ulcers, jaundice and abdominal distension (due to splenomegaly).
Investigations
Red cells are small, thin and misshapen, and
have a characteristic resistance to osmotic lysis. In the more severe forms
nucleated red cells and other immature blood cells are seen. The final diagnosis
is by haemoglobin electrophoresis.
Treatment
Blood transfusion may be necessary to correct
profound anaemia. Splenectomy is occasionally of benefit in patients who require
frequent blood transfusion — particularly if they have developed haemolytic antibodies from repeated
transfusion —
and where the
bulky spleen is uncomfortable or painful.
Sickle
cell disease
Sickle cell disease is a hereditary haemolytic
anaemia, occurring mainly among those of African origin, in which the normal
haemoglobin A is replaced by haemoglobin S (HbS). The HbS molecule crystallises
when the blood oxygen tension is reduced and this distorts and elongates the
red cell. This increases blood viscosity and obstructs flow of blood through
both the ‘open’ and ‘closed’ circulations in the spleen, and through
other blood vessels. Splenic microinfarcts, splenomegaly and, later,
autosplenectomy develop. This is associated with reduced antibody production and
a reduced ability to filter bacteria — especially
Streptococcus pneumoniae — in the spleen.
Clinical
features
The sickle cell trait can be detected in 9 per
cent of those of African origin but most are asymptomatic; sickle cell disease
occurs in about 1 per cent of Africans. Depending on the vessels affected by the
vascular occlusion, patients may have bone or joint pain, priapism, neurological
abnormalities, skin ulcers or abdominal pain due to visceral blood stasis.
Investigations
Characteristic sickle-shaped cells can be seen
in a blood film, but this has been replaced by haemoglobin electrophoresis.
Treatment
Hypoxia, which provokes a sickling crisis,
should be avoided, and particular care taken in patients with sickle cell
anaemia undergoing general anaesthesia. Adequate hydration and partial exchange
transfusion may help in a crisis. Splenectomy is of benefit in a few patients
where excessive splenic sequestration of red cells aggravates the anaemia. This
hypersplenism may be chronic, which usually occurs in late childhood or
adolescence, or acute, which occurs in the first 5 years of life and may
be precipitated by Streptococcus pneumoniae infection. Acute attacks of
hypersplenism can usually be treated with packed red cell transfusion, but
occasionally splenectomy is of benefit.
Hypersplenism
This is an indefinite term which includes
splenic enlargement, any combination of anaemia, leucopenia or thrombocytopenia,
compensatory bone marrow hyperplasia and improvement after splenectomy. The
vagueness of the definition implies careful clinical judgement between surgeon
and haematologist to determine when long- and short-term risks of splenectomy
are less than those of continued conservative management.