Shivangi Mistry, M.Pharm in Pharmacology, Assistant Professor in BMCP, Introduction, epidermiology, etiology, pathophysiology, diagnosis, treatmet

1. MS. SHIVANGI MISTRY
M.PHARM (PHARMACOLOGY)
ASSISTANT PROFESSOR
BHAGWAN MAHAVIR COLLEGE OF PHARMACY
Date : 27-8-20 time : 10: 00 am 1

2. content
INTRODUCTION
Epidermiology
Aetiology
Pathophysiology
Investigations
Treatment
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3. INTRODUCTION
• In the haemolytic anaemias there is a reduced
lifespan of the erythrocytes.
• If the rate of destruction of the erythrocytes exceeds
the rate of production, then anaemia results.
• There are a wide range of haemolytic anaemias with
both genetic and acquired disorders.
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7. epidermiology
A. Sickle cell anaemia
• Sickle cell disease is a hereditary condition of which several
different variants of exist.
• In the UK approximately 5000 people, largely from the
Afro-Caribbean population, have sickle cell disease
B. Thalassaemias
• North and West Africa, the Middle East and the Indian
subcontinent.
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8. • More than 100 β thalassaemia mutations have been
identified and they tend to produce severe anaemia.
C. Glucose-6-phosphate dehydrogenase deficiency
anaemia
• About 300 million people in the world are affected by
glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• The most common form of G6PD deficiency is found in
15% of black Americans.
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9. Aetiology
A. Sickle cell anaemia
• Those with the most common variant of sickle cell disease
have haemoglobin S (Hb S) (normal haemoglobin is usually
designated Hb A).
• Haemoglobin S has valine substituted for glutamic acid as
the sixth amino acid in the β-polypeptide compared with
normal haemoglobin.
• Patients with homozygous Hb S develop many problems
including anaemia. 9

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11. • Sickle cell trait is where a person is a carrier of the
gene (heterozygous for the sickle cell gene).
• These people are usually asymptomatic.
• The offspring from a father with trait and a mother
with trait has a 1 in 4 chance of having sickle cell
disease. (fig).
• AA- normal, AS- sickle cell trait (hetrorozygous),
SS- Sickle cell dieases (homozygous)
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14. B. Thalassaemias
• In a thalassaemia there is either no a chain production (a
thalassaemia) or reduced production of a chain (at
thalassaemia).
• Heterozygotes are usually symptomless while
homozygotes are more severely affected, as are compound
heterozygotes in which there is a thalassaemia gene and a
gene from another haemoglobin variant (e.g. Hb S).
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15. C. G6PD deficiency
• There are a large number of variants of G6PD activity
found in different populations and ethnic groups.
• G6PD is an erythrocyte enzyme that is indirectly involved
in the production of reduced glutathione.
• Glutathione is produced in response to, and protects red
cells from, oxidizing reagents.
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16. Pathophysiology
A. Sickle cell disease
• The membrane of red cells containing Hb S is damaged,
which leads to intracellular dehydration.
• In addition, when the patient's blood is deoxygenated,
polymerization, of Hb S occurs, forming a semisolid gel.
• These two processes lead to the formation of crescent-
shaped cells known as sickle cells.
• Sickle cells are less flexible than normal cells (flexibility
allows normal cells to pass through the microcirculation).16

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18. • The inflexibility leads to impaired blood flow through the
microcirculation, resulting in local tissue hypoxia.
• Anaemia results from an increased destruction of red cells.
• Some red cells in patients with sickle cell disease contain
fetal haemoglobin (Hb F). These cells do not sickle.
B. Thalassaemias
a) β thalassaemias
• In β thalassaemias there is a reduced or absent production
of the globin β chain.
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19. • This leads to a relative excess of α chain which,
when unpaired, become unstable and precipitates in
the red cell precursors.
• There is ineffective erythropoiesis and those mature
cells that reach the circulation have a shortened life
span.
b) α thalassaemias
• The deficiency of α chains leads to an excess of γ
or β chains. 19

20. • This time erythropoiesis is less affected but the
haemoglobin produced (haemoglobin Bart's or
Haemoglobin H) is unstable when the cells are in
the circulation and precipitates as the cells grow
older.
• This leads to a shortened lifespan with the spleen
trapping many of the cells.
• Haemoglobin Bart's and haemoglobin H are also
physiologically useless.
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21. C. G6PD deficiency
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23. • G6PD is essential for the production of the reduced form of
phosphorylated nicotinamide-adenine dinucleotide
(NADPH) in erythrocytes.
• If there is a deficiency in G6PD this decreases the
production of NADPH.
• NADPH is needed to keep glutathione in a reduced form.
Reduced glutathione maintains haemoglobin in a reduced
form and helps erythrocytes deal with oxidative stress.
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24. • Hence in G6PD deficiency, if the erythrocytes are exposed
to an oxidizing agent, the haemoglobin becomes oxidized
and forms what are known as Heinz bodies.
• The cell membrane is damaged and some of the red cells
haemolyse and others have their Heinz bodies removed by
the spleen to form 'bite cells'.
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25. Investigations
A. Sickle cell disease
• Abnormal haemoglobin can be detected using
electrophoresis.
• The proportion of Hb S is a useful monitoring parameter.
• Regular serum ferritin determinations identify the need for
desferrioxamine therapy and are used to monitor progress.
B. Thalassaemia
• For β thalassaemia the diagnosis is relatively
straightforward: haemolytic anaemia from infancy and racial
background.
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26. • Haemoglobin electrophoresis is used to determine the amounts
of abnormal haemoglobin.
C. G6PD deficiency
• The history and the clinical findings steer the diagnosis, which
is then confirmed by measuring G6PD activity.
• Care must be taken during the acute phase since there are
increased numbers of young cells with higher levels of activity
that may be misleading.
• The increased numbers of young cells result from the selective
destruction of older cells and the increased production of
reticulocytes. 26

27. Treatment
A. Sickle cell anaemia
• Patients with sickle cell disease have a high incidence of
pneumococcal infections and a number of studies have
shown the benefit of prophylactic antibiotics.
• Penicillin V (phenoxymethyl penicillin) 250 mg twice a
day is usual for adults, erythromycin being used for
patients allergic to penicillin.
• Administration of pneumococcal vaccine and Haemophilus
influenzae vaccine is now common. 27

28. • Attempts have been made to increase the proportion of Hb F
and reduce the proportion of Hb S in the circulation.
• Several drugs have been shown (some only in animal
models) to stimulate fetal haemoglobin production.
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29. • Hydroxycarbamide (hydroxyurea) is effective and may
reduce the frequency of crises but is limited by its
cytotoxicity.
• Transfusions and exchange transfusions have also been used
to decrease the proportion of Hb S.
• This is limited by the usual complications of chronic
infusions: iron overload, the risk of blood-borne virus
transmission and sensitization.
• Appropriate antibiotic therapy should be started at the first
signs of infection. 29

30. • Strong opioids are required for pain relief.
• Traditionally many patients have been given frequent
intramuscular injections of pethidine.
• Morphine is a more logical choice of opioid, and some
centres are having success with morphine in a
patientcontrolled analgesia system (PCAS).
B. Thalassaemia
• Many patients with severe forms are transfusiondependent
from an early age, which inevitably leads to iron overload.
Desferrioxamine and deferiprone are routinely needed.30

31. • As in sickle cell disease, much attention is being placed on
the idea of switching the bone marrow to the production of
fetal haemoglobin rather than the defective adult
haemoglobin of β thalassaemia but these therapies are still
in the early stages of development.
• It is likely that a combination of drugs, hydroxycarbamide
(hydroxyurea) and erythropoietin, will provide some clinical
improvement.
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32. C. G6PD deficiency
• In cases of acute haemolytic anaemia the causative
oxidizing agent should be stopped and general supportive
measures adopted.
• Blood transfusions may be necessary.
• Vitamin E (an antioxidant) appears to have little clinical
benefit in preventing haemolysis.
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