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 operation is recommended has been decreasing. If it is not imperative before, the optimum time seems to be about 7 years of age, before gallstones have had time to form but subsequent vulnerability to infection is reduced. Ultrasono­graphy should be performed preoperatively to determine the presence or absence of gallstones.

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.