Page 478 - Medicine and Surgery

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474 Chapter 12: Haematology and clinical immunology

functional abnormality of any of the membrane proteins Incidence
(spectrin, ankyrin, protein 4.1). Part of the abnormally Most common haemoglobinopathy.
weak cell membrane is removed as the cells pass through
the spleen, changing the cell shape from a biconcave disc Age
to asphere. These cells are more rigid than normal and As HbF synthesis is normal, it presents at 6 months.
are subject to further damage in the microcirculation.
Sex
Clinical features M = F
Spherocytosis may present as neonatal jaundice or
anaemia with chronic malaise and splenomegaly. Nor- Geography
mal infections cause a relative increase in haemolysis and Occurs most frequently in Africa, Middle East, India and
may result in jaundice. Complications as for haemolytic the Mediterranean.
anaemia may occur (see page 473).
Aetiology
Investigations
Apoint mutation on chromosome 11 results in a sub-
Anaemia is usually mild. A blood film will demonstrate
stitution valine for glutamine at the sixth codon on the
the spherocytes, but this cell morphology is not diagnos-
β globin chain to form haemoglobin (Hb)S. Infection,
tic.Thediagnosiscanbeconfirmedbydemonstratingthe
dehydration, hypoxia and cold may precipitate a sickle
osmotic fragility of the red blood cells.
crisis. Classical sickle cell anaemia is a result of the pres-
ence of two mutations, i.e. HbSS, other combinations
Management
that produce sickle cell anaemia include Sβ thal, SD, SE
Splenectomy is often required but should be delayed to
and SC variants.
adulthood if possible to prevent overwhelming septi-
caemia from encapsulated organisms. Patients are given
Pathophysiology
pneumococcal vaccinations and prophylactic antibiotics
HbS molecules, when deoxygenated tend to aggregate
post splenectomy.
into rigid polymers. The red blood cells become inflex-
ible and sickle shaped and become trapped in the mi-
Haemoglobinopathies crocirculation, especially within bones, resulting in mi-
Haemoglobinopathies are abnormalities in the nor- crovessel occlusion.
mal structure of the haemoglobin molecule. Normal
haemoglobin is made up of four polypeptide chains Clinical features
each containing a haem group. HbA is the main adult Sickle cell trait (the carrier state) is asymptomatic, but
form comprising two α chains and two β chains. Adults offers protection against falciparum malaria. Sickle cell
also have a minor haemoglobin HbA 2 ,which makes up anaemia is a clinical spectrum ranging from asymp-
around 2% of the circulating haemoglobin and con- tomatic to severe haemolytic anaemia and recurrent
sists of two α chains and two δ chains. Abnormal sickle crises. Painful vascular occlusive crises typically
haemoglobins result from: produce symptoms of bone pain and pleuritic chest pain
Abnormal globin chain production such as thalas-
with a low-grade fever. Severe occlusive crises may result
saemia. in seizures and hemiparesis due to cerebral vessel occlu-
Abnormal structure of the globin chain in sickle cell
sion, haematuria due to occlusion of the renal micro-
disease. circulation, priapism, splenic infarcts and liver damage.
Other patterns of crisis:
Acute sequestration (pooling of blood in liver and
Sickle cell anaemia
spleen) requires transfusion for apparent hypo-
Definition volaemia.
Autosomal recessive condition in which there is abnor- Pulmonary infarction may occur in association with
mal structure of the globin chain. pneumonitis termed acute chest syndrome.