SICKLE CELL DISEASE BY ANUBHA MA'AM. FULL DETAIL

SICKLE CELL
DISEASE
BY
ANUBHA KUMARI
ADMIN HEAD AND ASSISTANT PROFESSOR
ANNADA COLLEGE
VINOBA BHAVE UNIVERSITY HAZARIBAGH JHARKHAND

INTRODUCTION
 Sickle cell disease affect millions of people world wide
 • The highest prevalence is among people of Africa,
southern America, Arabian peninsula and Mediterranean
countries
 • 25 to 30% of neonates in western Africa are carriers of
sickle cell trait
 • Affected patients characteristically are asymptomatic
until 4 to 6 months of age
 In South Asia, the highest prevalence of the disease is in
India, where over 20 million patients with SCD live. (CDC)

CONT.
 Sickle cell disease is a genetic disorder in which red blood
cells contort into a sickle shape. The cells die early, leaving a
shortage of healthy red blood cells (sickle cell anemia) and
can block blood flow causing pain (sickle cell crisis).
 Sickle cell anaemia is a serious disease in which the body
makes sickle-shaped ("c"-shaped) red blood cells.
 Normal red blood cells are disk-shaped and move easily
through your blood vessels. Red blood cells contain the
protein haemoglobin.
 .

 Sickle cells contain abnormal haemoglobin that causes
the cells to have a sickle shape, which don't move easily
through the blood vessels - they are stiff and sticky and
tend to form clumps and get stuck in the blood vessels.
 The clumps of sickle cells block blood flow in the blood
vessels that lead to the limbs and organs. Blocked blood
vessels can cause pain, serious infections, and organ
damage

HISTORY
 The disease originated in at least 4 places in Africa,
Mediterranean countries (such as Turkey, Greece, and
Italy), and in the Indian/Saudi Arabian subcontinent. It
exists in all countries of Africa and in areas where Africans
have migrated.

Characteristi
cs of sickle
cells
RBCS
 120 day life span
 Hb has normal oxygen carrying capacity
 12-14 g/dl of Hb
SICKLED CELLS
 30-40 day life span
 Hb has decreased oxygen carrying capacity
 6-9 g/dl of Hb

CONT
 • Sickle cell is a genetic disorder caused by an autosomal
recessive single gene defect in the B- globin chain of HbA
 • Complete Hb molecule consist of four separate chains of
amino acids joined together
 ➤ Alpha chain (2)
 ➤Beta chain (2)
 ➤ Each chain is alike with similar sequence of amino acids

8
ETIOLOGY
 In Haemoglobin,
Alpha chain = 141 Amino acids
Beta chain = 146 Amino acids
When the 6th
Amino acid (Glutamic acid) in the Beta chain of Haemoglobin
replaced by Valine leads to sickle cell Anemia.
 Mutant haemoglobin polymerises which sticks together and form bundle of
long rods.
 They tends to block the blood flow in the blood vessels of organs and limbs
and it cause pain and organ damage.
 The sickle shaped cell break apart easily causing Anemia.

 Hemoglobins bind oxygen in a cell, but amino
acids can switch with betaglobins making the cell
nonfunctional

 • In sickle cell Hb, the two alpha chains are normal.
 • The effect of mutation resides only in the Beta chain
where amino acid glutamic is replaced by hydrophobic
amino acid valine

 It is a severe, chronic, hereditary haemolytic disorder due
to the homozygous presence of haemoglobin S, usually
characterized by pallor and recurrent crises.
 • Is heredity blood disorder of the RBC that assumes an
abnormal rigid sickle shape characterized by s/s of
anaemia and recurrent crises

14
PATHOPHYSIOLOGY
 The membrane of red cells containing hemoglobin S is damaged, which leads
to intracellular dehydration.
 In addition, when the patient's blood is deoxygenated, polymerization of
hemoglobin 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).
 The inflexibility leads to impaired blood flow through the microcirculation,
resulting in local tissue hypoxia.
 Anemia results from an increased destruction (hemolysis) of red cells in the
spleen.

Types of
Sickle Cell
Disorder
 • There are basically three, i.e.
 Sickle cell disease (sickle cell Anaemia): There is
autosomal recessive (homozygous) inheritance (Hb SS). It
is symptomatic.
 Sickle cell trait: There is heterozygous inheritance of Hb S
from one parent (Hb AS). It is asymptomatic.
 Sickle cell syndromes: Associated with presence of Hb S
(Hb SC sickle cell Hb C) HBSD (Sickle cell Hb D)
 NOTE: Concentrate on Sickle cell Disease and sickle cell
trait)

Genetic
transmission
 • If one parent has sickle cell trait (HbAS) and the other
does not carry the sickle hemoglobin at all (HbAA) then
none of the children will have sickle cell anemia.
 • There is a one in two (50%) chance that any given child
will get one copy of the HbAS gene and therefore have the
sickle cell trait.
 • It is equally likely that any given child will get two HbAA
genes and be completely unaffected.

 If one parent has sickle cell trait (HbAS) and the other does
not carry the sickle hemoglobin at all (HbAA) then none of the
children will have sickle cell anemia.
 There is a one in two (50%) chance that any given child will get
one copy of the HbAS gene and therefore have the sickle cell trait.
 It is equally likely that any given child will get two HbAA genes
and be completely unaffected.

 If both parents have sickle cell trait (HbAS) there is a one in
four (25%) chance that any given child could be born with sickle
cell anemia.
 There is also a one in four chance that any given child could be
completely unaffected.
 There is a one in two (50%) chance that any given child will get
the sickle cell trait.

 If one parent has sickle cell trait (HbAS) and the other has
sickle cell anaemia (HbSS) there is a one in two (50%) chance
that any given child will get sickle cell trait and a one in two (50%)
chance that any given child will get sickle cell anemia.
 No children will be completely unaffected.

 If one parent has sickle cell anaemia (HbSS) and the other is
completely unaffected (HbAA) then all the children will have
sickle cell trait.
 None will have sickle cell anemia.
 The parent who has sickle cell anemia (HbSS) can only pass the
sickle hemoglobin gene to each of their children.

24
CLINICAL MANIFESTATION
 Chronic Anaemia
 Arthralgia – Pain in joints
 Anorexia – less appetite
 Fatigue
 Splenomegaly
 Fever
 Frequent infection
 Episodes of pain in chest, abdomen and joints
 Vision problems
 Weakness and Pallor
 Dehydration

25
COMPLICATIONS
 Acute Complications
 Fever and Infection
 Acute chest syndrome (ACS), defined as a new pulmonary infiltrate
associated with fever and/or respiratory symptoms, is the second most
common cause of hospitalization and leading cause of deaths among
individuals with SCD.
 Priapism- prolonged erection of the penis.
 Sickle Cell Pain
 Splenic sequestration is the sudden massive enlargement of the spleen
resulting from the sequestration of sickled RBCs in the splenic parenchyma.
 Venous Thromboembolism

26
 Chronic Complications
 Pulmonary hypertension
 Airway inflammation
 Hyper-responsiveness
 Skeletal and Skin Diseases
 Ocular Manifestations
 Hepatobiliary Diseases
 Cardiac Diseases
 Cardiac Diseases

27
DIAGNOSIS
COMPLETE BLOOD COUNT:
 Hb- Low level of Hb ( 6-8g/dl)
 RBC Count- Decreased
 Hematocrit value- Decreased
 Reticulocyte count – Increased
 Presence of Auto Antibodies

33
1. Routine Health Maintenance
 SCD is a complex chronic disease involving multiple organs.
 In addition to the preventive care recommended for the general population,
individuals with SCD also need health maintenance and screenings that
focus on minimizing complications.
2. Immunizations
 Administration of routine immunizations is crucial preventive care in
managing SCD. Children 6 months and older and adults with SCD should
receive influenza vaccine annually.
 Two different pneumococcal vaccines are available.
 The 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar®)
induces good antibody responses in infants and children less than 2 years of
age.

34
 Immunization with the PCV13 is recommended for all children, regardless of
SCD status, younger than 24 months of age.
 Infants should receive the first dose after 6 weeks of age.
 Two additional doses should be given at 2-month intervals, followed by a
fourth dose at age 12 to 15 months.
 The 23-valent pneumococcal polysaccharide vaccine (PPSV23;
Pneumovax®23) is recommended for all children with functional or acquired
asplenia but must be given after 2 years of age because of poor antibody
response.
 A booster dose of PPSV23 is recommended 5 years after the first dose. Both
pneumococcal vaccines are recommended for adults with certain medical
conditions, including SCD.

35
 The risk of meningococcal disease is also higher in SCD and vaccination is
recommended for individuals with functional or acquired asplenia.
 Two types of meningococcal vaccines are available:
(1) Quadrivalent
(2) Meningococcal group B vaccine.
3. Penicillin
 Penicillin prophylaxis until at least 5 years of age is recommended in children
with SCD, even if they have received PCV13 or PPSV23 immunization, as
prophylaxis against invasive pneumococcal infections.
 An effective regimen that reduces the risk of pneumococcal infections by 84%
is penicillin V potassium at a dosage of 125 mg orally twice daily until the
age of 3 years, followed by 250 mg twice daily until the age of 5 years.

36
 Individuals who are allergic to penicillin can be given erythromycin 20
mg/kg/day.
4. Hydroxyurea
 The starting dose for adult is 15 mg/kg/day rounded to the nearest 500 mg as
a single daily dose.
 A lower dose of 5 to 10 mg/kg/day is used for patients with chronic disease.
 The recommended dose for children is 20 mg/kg.
 Dosage can be increased by 5 mg/kg up to a maximum of 35 mg/kg in 8-week
intervals if the patient does not demonstrate significant adverse effects and
blood counts are stable.
 Patients receiving HU should be closely monitored for toxicity.
 Blood counts should be checked every 4 weeks during dose titration and every
8 weeks thereafter.

37
 Treatment should be interrupted if hematologic indices fall below the
following values:
 Absolute neutrophil count, 2,000 cells/mm3 (2 × 10 9 /L)
 Platelet count, 80,000 cells/mm3 (80 × 10 9 /L)
 Hemoglobin, 5 g/dl (50 g/L; 3.1 mmol/L)
 Reticulocytes, 80,000 cells/mm3 (80 × 10 9 /L)
 If the hemoglobin concentration is less than 9 g/dl (90 g/L; 5.59
mmol/L)

38
5. Glutamine
 Sickled RBCs are susceptible to oxidative damage leading to hemolysis and
vasoocclusion.
 Glutamine, an essential amino acid, is a precursor for nicotinamide adenine
dinucleotide (NAD+ ) synthesis.

39
 Early studies have shown increased uptake of glutamine by sickle RBCs,
mainly to produce NAD+.
 Children with SCD have lower glutamine levels; an increase of NAD+ can
potentially restore the redox balance in oxidative stressed cells.
 L-glutamine (Endari®) was FDA-approved in July 2017, becoming the first
product approved for pediatric patients with SCD and the first new treatment
for adults in almost 20 years.
 It is indicated for SCD patients age 5 and older to reduce the acute
complications of SCD.
 The product is available in 5-g packets and should be mixed with 8 ounces of
liquid (~240 mL) or 4 to 6 ounces (~110- 170 g) of food.
 The recommended dose is based on weight: 5 g twice a day for less than 30 kg;
10 g twice a day for 30 to 65 kg and 15 g twice a day for greater than 65 kg.
The most common gastrointestinal side effects are constipation, abdominal
pain, and nausea.

40
6. Iron chelators
 Patients who require RBC transfusion become Iron overloaded and leads to
toxicity to several vital organs.
 Iron can be removed using Iron chelators.
 Desferrioxamine (IV/SC for 5-7 days in a week)
 Deferasirox
 Deferiprone

TREATMENT
Antibiotics e.g. e.g. Crystapen Penicillin 1-2mu
qid for 5/7
Oxygen therapy to relieve hypoxemia e.g.
5l/minute
Narcotic analgesics like pethidine 0.5-2mg/kg for
3/7
Folic acid 5-10 mg od for 14/7
Blood transfusion with packed cell may be given

TREATMENT CONT
IV fluid with normal saline to relieve
dehydration
Hydroxurea used to reduce number of
episodes

COMPLICATIONS
Opioid tolerance, which can occur as a normal,
physiologic response to the therapeutic use of
opiates leading to addiction
Stroke, which can result from a progressive
narrowing of blood vessels, preventing oxygen
from reaching the brain.
Chronic renal failure due to Sickle cell
nephropathy
Acute papillary necrosis in the kidneys.

COMPLICATIONS
Cholelithiasis (gallstones) and cholecystitis,
which may result from excessive bilirubin
production and precipitation due to prolonged
haemolysis.
Priapism and infarction of the penis.
Leg ulcers.
In eyes, background retinopathy, proliferative
retinopathy, vitreous haemorrhages and retinal
detachments, resulting in blindness.

COMPLICATIONS
Avascular necrosis (aseptic bone necrosis) of the
hip and other major joints, which may occur as a
result of ischaemia.
Pulmonary hypertension (increased pressure on
the pulmonary artery), leading to strain on the
right ventricle and a risk of heart failure
Decreased immune reactions due to
hyposplenism (malfunctioning of the spleen)

PREVENTION
Identify what can trigger the “Crisis” such as
stress, avoid extremes of heat and cold weather,
don’t travel airplane that is not cabin pressurized
Maintain healthy lifestyle habits
Eating healthy
Avoid dehydration
Exercise regularly
Get enough sleep and rest
Avoid alcohol and don’t smoke
Regular medical checkups and treatment are
important

Sickle Cell
Anemia
News
 Hydroxyurea Significantly Reduces Infections in Children
With Sickle Cell Anemia
 Jan. 29, 2024 — Researchers have revealed that
hydroxyurea significantly reduces infections in children
with sickle cell anemia.
 New Research Advances Understanding of Cancer Risk in
Gene Therapies
 Nov. 16, 2023 — Researchers have discovered that 'cell
competition' following gene therapy results in the
accumulation of stem cells with genetic mutations which
make them grow faster.

Sickle Cell
Anemia
News
 Researchers Chart the Contents of Human Bone Marrow
 Nov. 14, 2023 — A team has mapped the location and
spatial features of blood-forming cells within human bone
marrow. Their findings confirm hypotheses about the
anatomy of this tissue and provide a powerful new means
to study diseases
 Promising Evidence for Sickle Cell Gene Therapy
 Aug. 30, 2023 — A clinical trial has tested a potentially
curative stem cell gene therapy for sickle cell disease.

REFERENCES
1. Pharmacotherapy: A Pathophysiologic approach, Joseph T
Dipiro, Thomas D Nolin.., 11th
edition. Page No: 4942- 4972,
5054-5100.
2. Clinical Pharmacy and Therapeutics by Roger Walker. Page No:
784-790.

SICKLE CELL DISEASE BY ANUBHA MA'AM. FULL DETAIL

SICKLE CELL DISEASE BY ANUBHA MA'AM. FULL DETAIL

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SICKLE CELL DISEASE BY ANUBHA MA'AM. FULL DETAIL