Page 335 - Textbook of Pathology, 6th Edition

2.Mechanism of sickling: During deoxygenation, the red 319
cells containing HbS change from biconcave disc shape to
an elongated crescent-shaped or sickle-shaped cell. This
process termed sickling occurs both within the intact red cells
and in vitro in free solution. The mechanism responsible for
sickling upon deoxygenation of HbS-containing red cells is
the polymerisation of deoxygenated HbS which aggregates
to form elongated rod-like polymers. These elongated fibres
align and distort the red cell into classic sickle shape.
3. Reversible-irreversible sickling: The oxygen-dependent
sickling process is usually reversible. However, damage to
red cell membrane leads to formation of irreversibly sickled
red cells even after they are exposed to normal oxygen
tension.
4.Factors determining rate of sickling: Following factors
determine the rate at which the polymerisation of HbS and CHAPTER 12
consequent sickling take place:
i) Presence of non-HbS haemoglobins: The red cells in patients
of SS have predominance of HbS and a small part consists of Figure 12.29 Sickle cell anaemia. PBF shows crescent shaped
non-HbS haemoglobins, chiefly HbF (2-20% of the total elongated red blood cells, a few target cells and a few erythroblasts.
haemoglobin). HbF-containing red cells are protected from
sickling while HbA-containing red cells participate readily growth and development and increased susceptibility to
in co-polymerisation with HbS. infection due to markedly impaired splenic function.
ii) Intracellular concentration of HbS.
LABORATORY FINDINGS. The diagnosis of SS is
iii) Total haemoglobin concentration.
considered high in blacks with haemolytic anaemia. The
iv) Extent of deoxygenation.
laboratory findings in these cases are as under (Fig. 12.29):
v) Acidosis and dehydration.
1. Moderate to severe anaemia (haemoglobin concen-
vi) Increased concentration of 2, 3-BPG in the red cells. tration 6-9 g/dl).
CLINICAL FEATURES. The clinical manifestations of homo- 2. The blood film shows sickle cells and target cells and
zygous sickle cell disease are widespread. The symptoms features of splenic atrophy such as presence of Howell-
begin to appear after 6th month of life when most of the HbF Jolly bodies.
is replaced by HbS. Infection and folic acid deficiency result 3. A positive sickling test with a reducing substance such
in more severe clinical manifestations. These features are as as sodium metabisulfite (described above).
under: 4. Haemoglobin electrophoresis shows no normal HbA
1. Anaemia. There is usually severe chronic haemolytic but shows predominance of HbS and 2-20% HbF.
anaemia (primarily extravascular) with onset of aplastic crisis Double Heterozygous States Introduction to Haematopoietic System and Disorders of Erythroid Series
in between. The symptoms of anaemia are generally mild
since HbS gives up oxygen more readily than HbA to the Double heterozygous conditions involving combination of
tissues. HbS with other haemoglobinopathies may occur. Most
S thal
2. Vaso-occlusive phenomena. Patients of SS develop common among these are sickle-β-thalassaemia (β β ),
recurrent vaso-occlusive episodes throughout their lives due sickle C disease (SC), and sickle D disease (SD). All these
to obstruction to capillary blood flow by sickled red cells disorders behave like mild form of sickle cell disease. Their
upon deoxygenation or dehydration. Vaso-obstruction diagnosis is made by haemoglobin electrophoresis and
affecting different organs and tissues results in infarcts which separating the different haemoglobins.
may be of 2 types: OTHER STRUCTURAL HAEMOGLOBINOPATHIES
i) Microinfarcts affecting particularly the abdomen, chest, Besides sickle haemoglobin, about 400 structurally different
back and joints and are the cause of recurrent painful crises abnormal human haemoglobins have been discovered in
in SS. different parts of the world. Some of them are associated with
ii) Macroinfarcts involving most commonly the spleen clinical manifestations, while others are of no consequence.
(splenic sequestration, autosplenectomy), bone marrow A few important and common variants are briefly described
(pains), bones (aseptic necrosis, osteomyelitis), lungs below:
(pulmonary infections), kidneys (renal cortical necrosis), CNS
(stroke), retina (damage) and skin (ulcers), and result in HbC Haemoglobinopathy
anatomic and functional damage to these organs. HbC haemoglobinopathy is prevalent in West Africa and in
3. Constitutional symptoms. In addition to the features of American blacks. The molecular lesion in HbC is substitution
anaemia and infarction, patients with SS have impaired of lysine for glutamic acid at β-6 globin chain position. The