ANEMIA

AMEENA KADAR K A
FIRST SEM M PHARM
PHARMACY PRACTICE
SANJO COLLEGE OF
PHARMACEUTICAL STUDIES
ANEMIA:
 It is a group of diseases characterized by a decrease in either hemoglobin
(Hb) or the volume of red blood cells (RBCs), which results in decreased
oxygen- carrying capacity of the blood.
 Anemia is defined by the World Health Organization (WHO) as Hb
less than 13 g/dL (less than 130 g/L; less than 8.07 mmol/L) in men
and less than 12 g/dL (less than 120 g/L; less than 7.45 mmol/L) in women.
 Children of both sexes below 14 years of age have lower levels, the cut-off
for anemia being 11 g/dL in those aged 6 months to 6 years and 12 g/dL in the
6–14 age group.
 Anemia is not one disease, but a condition that results from a number
of different pathologies.
2
 EPIDEMIOLOGY

 Anemia is possibly one of the most common conditions in the world

and results in significant morbidity and mortality, particularly in the
developing world.
 Worldwide, over 50% of pregnant women and over 40% of infants
are anemic.
 The prevalence of anemia among six groups as per the National Family
Health
Survey 5 (2019-21), is 25.0 percent in men (15-49 years) and 57.0 percent
in
women (15-49 years). 31.1 percent in adolescent boys (15-19 yrs), 59.1
percent in adolescent girls, 52.2 percent in
pregnant women (15-49 years) and
3
67.1percent in children (6-59 months).
 o A hematocrit test measures the proportion of red blood cells in your
blood.
Male = <42%.
Female = <37%.

4
 CLASSIFICATION OF ANEMIA
 Anemia can be classified on the basis
of
 Morphology of the RBCs
 Etiology
 Pathophysiology
 Physiology.

5
 MORPHOLOGICAL CLASSIFICATION OF
ANEMIA

6
 ETIOLOGICAL CLASSIFICATION OF ANEMIA

Iron
Vitamin B12
Folic acid
Pyridoxine
Deficiency
Bleeding
(hemorrhage)
Hemolysis
(hemolytic
Etiological Peripheral
anemia)
classification
of Anemia

Anemia of chronic
disease
Impaired Bone
Anemia of the
Marrow elderly
Function
Malignant bone
marrow
disorders

7
 PATHOPHYSIOLOGICAL CLASSIFICATION OF
ANEMIA

ANEMIA BASED ON
PATHOPHYSIOLOG
Y

INADEQUATE
EXCESSIVE CHRONIC ENHANCED RBC
PRODUCTION OF
BLOOD LOSS HEMORRHAGE DESTRUCTION
RBC

Recent hemorrhage Vaginal bleeding

Trauma Peptic ulcer

Hemolytic anemia Aplastic anemia
Intestinal parasites
Peptic ulcer
Aspirin and other
Gastritis
NSAIDs
Hemorrhoids

8
 PHYSIOLOGIC CLASSIFICATION OF
ANEMIA

9
 ETIOLOGY

The low hemoglobin level that defines anemia results from two
different mechanisms:
• Increased hemoglobin loss due to either: – hemorrhage (red cell loss) or
–
hemolysis (red cell destruction).
• Reduced hemoglobin synthesis due to either: – lack of nutrient or –
bone
marrow failure.
• Host of systemic disorders such as infection, chronic renal diseases
or malignancy.

10
11
12
 Use of erythrocyte morphology in differential diagnosis of
anemia

13
 MICROCYTIC
ANEMIA

14
 IRON DEFICIENCY ANEMIA (IDA)
 Iron deficiency is a state of negative iron balance in which the daily iron
intake and stores are unable to meet the RBC and other body tissue needs.
 The body contains approximately 3.5 g of iron, of which 2.5 g are found in Hgb.
 A significant amount of iron is stored as ferritin or aggregated
ferritin (hemosiderin) in the reticulo-endothelial cells of the liver, spleen,
and bone marrow and by hepatocytes.
 Decreased level of ferritin and serum iron, as well as decreased
transferrin saturation.
 Hb and Hematocrit decrease later.
 Daily requirement of Iron 0.9mg in males, 2mg females, in pregnancy it is
3-
5mg and in infant it is 0.5mg.

15 postmenopausal femalesdietary
The daily recommended and 18allowance
mg in menstruating
for iron is 8 mg in adult males
females.
and
 EPIDEMIOLOGY
 Iron deficiency anemia is the commonest form of anemia worldwide and
may be present in up to 20% of the world's population.
 A diet deficient in iron, parasitic infestations, for example, hookworm
(causing
blood loss), and multiple pregnancies contribute to its high
prevalence in underdeveloped countries.
 Even in Western societies, it has been reported that as many as
20% of menstruating females show a rise in hemoglobin levels on iron
therapy

16
 Causes of Iron Deficiency
Anemia
 Blood Loss
• Menstruation
• Gastrointestinal (e.g., Peptic
ulcer)
• Trauma
 Decreased Absorption
• Medications
• Gastrectomy
• Regional enteritis
 Increased requirement
• Infancy
• Pregnant/lactating women
 Hereditary
17  Impaired Iron use
 PATHOPHYSIOLOGY OF
IDA
 Diminished total body iron content, developing in stages over a period
of negative iron balance.
Iron depletion – Stage One
Iron deficient erythropoiesis – Stage
Two Iron deficiency anemia – Stage
Three
 Stage One
Iron storage is exhausted - indicated by decrease in serum ferritin levels,
no anemia – RBC morphology is normal.
 Stage Two
Insufficient iron to insert into protoporphyrin ring to form heme –
Protoporphyrin
18
accumulates in cell and complexes with zinc to form ZPP, no anemia,
19
  Stage Three
All laboratory tests for iron status become abnormal, most significant finding
is microcytic, hypochromic anemia and there is hyperplasia of erythroids.
 Erythroid hyperplasia is a condition of excessive count of erythroid
precursor cells (in layman words, immature red blood cells) in the bone
marrow.

20
 Iron deficiency develops insidiously

Iron stocks deplete

Decline in serum ferritin and absence of stainable iron in bone

marrow

Decrease in serum iron and decrease in serum transferrin

Decrease synthesis of hemoglobin, myoglobin and other iron

containing
proteins

ANEMIA
21
 SIGNS OF IDA
 Pale skin and mucous membranes
 Painless glossitis (Inflammation of the tongue)
 Angular stomatitis (Red, swollen patches in the both corners of
mouth)
 Koilonychia (spoon shaped nails)
 Dysphagia (difficulty in
Chronic Iron
swallowing)
deficiency
 Pica (unusual cravings)
 Atrophic gastritis
 Poikilocytes

22
 Atrophic gastritis: Chronic
inflammation of gastric mucosa
with loss of gastric glandular cells.

Poikilocytes: Increase
in abnormal shape of
RBCs

23
 Plummer-Vinson syndrome (PVS)

 It is a rare condition characterized by the classic triad of dysphagia,

iron- deficiency anemia, and esophageal webbing.
 Plummer-Vinson syndrome is more common in middle-aged women and
is
associated with an increased risk of developing squamous cell carcinoma of
the pharynx and proximal esophagus.
 A disorder marked by anemia caused by iron deficiency, and a web-
like
growth of membranes in the throat that makes swallowing difficult.

24
 SYMPTOMS OF
IDA
1) Faintness
2) Fatigue
3) Dizziness
4) Irritability
5) Malaise
6) Palpitation
7) Headache
8) Shortness of
breath
9) Angina
10) Ankle edema

25
 LABORATORY DIAGNOSIS OF
ANEMIA

26
27
 MANAGEMENT OF IDA

Treatment Goals

 To Decrease Signs And

Symptoms

 Correct The Underlying Etiology

 Prevent Recurrence Of Anemia.

28
 A. NON- PHARMACOLOGICAL MANAGEMENT OF
IDA
 Iron rich diet
 Blood
Transfusion

29
 B. PHARMACOLOGICAL MANAGEMENT OF
IDA

IRON

PARENTERA
ORAL IRON L IRON

Ferrous sulphate
Iron-dextran
Ferrous gluconate
Iron-sorbitol-citric acid
Ferrous fumarate
Ferrous sucrose
Ferrous succinate
Ferric carboxymaltose
30
  ORAL IRON THERAPY
 Iron Salts
o Ferrous Sulphate
o Ferrous Fumarate
o Ferrous Gluconate
 200 mg elemental iron per day for 3-6 months.
 2-3 divided doses to maximize tolerability.
 Administration should be 1 hour before meals or on empty
stomach.
 Daily requirement of iron
• Male 0.5-1mg
• Female 1-2mg
• Pregnancy 3-5mg.

31
 Characteristics of various iron
formulations

32
 ORAL IRON
DOSING
 Ferrous sulphate given as oral dose, the usual dose for an adult is 325mg
(one tablet), administered 2-3 times a day
 However, due to limited absorption of iron by the intestinal walls, its
preferred
to administer lower doses of iron as its shown to be more effective with
less
side effects and improved compliance.
 The required daily dose may be calculated using the formula given,
with assumption that 0.25g/dL/day is the maximal rate of Hgb regeneration.
 Elemental iron(mg/day)= 0.25g Hgb/100mL blood/day
(5000mL blood)(3.4mg Fe/1g Hgb)
=40mg Fe/day/20% absorption (approximate absorption rate in
iron-deficient states)
33 =200mg Fe/day
=325mg TID ferrous
 ADR OF ORAL
IRON
 Epigastric pain
 Heart burn
 Nausea
 Vomiting
 Bloating
 Staining of teeth
 Metallic taste
 Constipation (More common- believed to be astringent action of iron)
 Abdominal pain.
 Patients should be warned that their faeces may become darker.
 Food interfere with iron absorption but sometimes administration with
food is recommended incase of GI symptoms.
34
 DRUG INTERACTIONS

35
 PARENTERAL IRON
THERAPY
Indications of therapy
o Intolerance to oral route
o Malabsorption
o Long term non adherence
o Patient with significant loss who transfusion and
blood refuse are
intolerant to oral therapy
o Chronic kidney disease
(CKD).
 Examples:
Iron dextran
Iron sucrose
Iron carboxymaltose

36
1. Iron-
dextran
 High Mol.wt colloidal solution containing 50 mg elemental iron/ml.
 It is the only preparation that can be injected I.M. as well as I.V.
 The total dose of iron dextran to be administered can be determined using the
following equation:
Iron (mg) = [Weight (pounds) ×
0.3] [100 −
{100(Hgb)/14.8}]
where Hgb is the patient’s measured
hemoglobin (g/dL).
 ADR:
a. Local: Pain at site of I.M. inj, pigmentation of skin, sterile abscess-
especially in old and debilitated patient.
b. Systemic: Fever, headache, joint pains, flushing, palpitation, chest
37
pain, dyspnea, lymph node enlargement.
 Parenteral Iron Preparations

38
 Hemochromatosis (Iron
 Iron overload is overload)
defined as excess stores of iron in the body.
 Excess iron is deposited in organs throughout the body.
 The most notable organs with iron deposition are the liver, heart, and
endocrine
glands.
 The resulting symptoms and disease are related to specific organ damage.
 The treatment for iron overload is reduction therapy. This is most
commonly
achieved through therapeutic phlebotomy.
 In patients with hemoglobin levels that do not tolerate therapeutic
phlebotomy, iron chelation therapy becomes an option.
 Desferoxamine (IV/SC) is an iron chelation therapy currently in use.
 It binds free iron and iron bound to ferritin.
39 An oral deferiprone is also beneficial but it causes reversible
 TREATMENT
ALGORITHM

40
 SICKLE CELL ANEMIA

 An inherited disease in which the red blood cells have an abnormal

crescent shape, block small blood vessels, and do not last as long as normal
red blood cells.
 Sickle cell anemia is caused by a mutation (change) in one of the genes
for hemoglobin (the substance inside red blood cells that binds to oxygen
and carries it from the lungs to the tissues).
 It is most common in people of West and Central African descent.

41
42
43
 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.

44
  Normal RBC Live for 120 days but sickle cell RBC live only 9-10
days

45
 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
46
the spleen.
  Some red cells in patients with sickle cell disease contain fetal hemoglobin (Hb
F).
 These cells do not become sickle cells.
 Drugs that may increase fetal hemoglobin
production:
• 5-Azacytidine
• Cytarabine
• Vinblastine
• Hydroxycarbamide
• Erythropoietin
• Short chain fatty acids (butyrates, valproate).

47
48
 INHERITANCE OF SICKLECELL DISEASE

• AA – Normal
• AS – Sickle cell trait
(heterozygous)
49 • SS – Sickle cell disease
(homozygous)
50
 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

51
 COMPLICATIONS
 Acute Complications
 Fever and Infection
 Acute chest (ACS), defined as a pulmonary infiltrate
syndrome new
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
52
  Chronic Complications

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

53
 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

54
55
 HAEMOGLOBIN ELECTROPHORESIS
(SICKLE CELL SCREENING)

• Used to confirm the Diagnosis

56
57
58
59
 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;
60 Prevnar®)
  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
61 medical
  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
62 the
 Individuals who are allergic to penicillin can be given erythromycin
20
mg/kg/day.
4. Hydroxyurea

63
  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.

64
  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)

65
66
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.

67
  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;
68 10 g twice a day for 30 to 65 kg and 15 g twice a day for greater than 65
and nausea.
 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 week)
a
 Deferasirox
 Deferiprone

69
70
71
72
73
74
75
 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.

76
THANK