Page 334 - Textbook of Pathology, 6th Edition

318 Patients with HbS are relatively protected against falciparum
malaria. Sickle syndromes occur in 3 different forms:
1. As heterozygous state for HbS: sickle cell trait (AS).
2. As homozygous state for HbS: sickle cell anaemia (SS).
3. As double heterozygous states e.g. sickle β-thalassaemia,
sickle-C disease (SC), sickle-D disease (SD).

Heterozygous State:Sickle Cell Trait
Sickle cell trait (AS) is a benign heterozygous state of HbS in
which only one abnormal gene is inherited. Patients with
AS develop no significant clinical problems except when they
become severely hypoxic and may develop sickle cell crises.

LABORATORY FINDINGS. These patients have no
anaemia and have normal appearance of red cells. But in
hypoxic crisis, sickle cell crises develop. The diagnosis is
Figure 12.27 The geographic distribution of major haemo- made by 2 tests:
globinopathies and thalassaemias. Thalassaemia and HbD are the 1. Demonstration of sickling done under condition of
haemoglobin disorders common in India.
reduced oxygen tension by an oxygen consuming reagent,
SECTION II
sodium metabisulfite.
in presentation from asymptomatic laboratory abnormalities
to intrauterine death. 2. Haemoglobin electrophoresis reveals 35-40% of the total
There are geographic variations in the distribution of haemoglobin as HbS.
various haemoglobinopathies world over as shown in Homozygous State:Sickle Cell Anaemia
Fig. 12.27. Major examples of these disorders are described
below. Sickle cell anaemia (SS) is a homozygous state of HbS in the
red cells in which an abnormal gene is inherited from each
parent. SS is a severe disorder associated with protean clinical
STRUCTURALLY ABNORMAL HAEMOGLOBINS
manifestations and decreased life expectancy.
SICKLE SYNDROMES PATHOGENESIS. Following abnormalities are observed
The most important and widely prevalent type of haemo- (Fig. 12.28):
globinopathy is due to the presence of sickle haemoglobin 1.Basic molecular lesion: In HbS, basic genetic defect is the
(HbS) in the red blood cells. The red cells with HbS develop single point mutation in one amino acid out of 146 in
‘sickling’ when they are exposed to low oxygen tension. haemoglobin molecule— there is substitution of valine for
Sickle syndromes have the highest frequency in black race glutamic acid at 6-residue position of the β-globin, producing
and in Central Africa where falciparum malaria is endemic. Hb α β .
s
2 2

Haematology and Lymphoreticular Tissues

Figure 12.28 Pathogenesis of sickle cell anaemia. A, Basic molecular defect. B, Mechanism of polymerisation and consequent sickling of red
cells containing HbS. C, Mechanism of sickling on oxygenation-deoxygenation.