Anemia In The Viewpoint Of Medical, Peadiatrics & Obstetrics

SEMINAR OF ANAEMIA
(PHYSIOLOGY)
By Group 3

COMPOSITION OF BLOOD
1. Cellular Portion (45% of
total blood volume)
-Erythrocytes (RBCs)
-Leukocyes (WBCs)
-Thrombocytes
2. Fluid portion (Plasma, 55%
of total blood volume)

Erythrocytes
Biconcave Disk
Flattened
Flexible
Semi-permeable
membrane
Contains Antigen
(ABO & Rh)  Blood
type
Anuclear
No Mitochondria

Erythrocytes
Life Span
100-120 days
FUNCTIONS
Transport O2
to tissues
Transport CO2
from tissues
Fate
Destroyed by
macrophage cells
(liver, spleen,
bone marrow)
33% of RBC cell
mass consist of
hemoglobin

Normal Erythrocytes
Normal Value
Male : 4.32 – 5.72 X 1012 cells/L
Female : 3.90 – 5.03 X 1012 cells/L
Source : myoclinic.org/test-
procedures/complete-blood-
count/basics/results/prc-20014088

Hemoglobin
Consist of 4 Globin
Adult (HbA) : 2α & 2β
Fetal (HbF) : 2α & 2γ
1 Heme bound to each
globin

Hemoglobin Normal Values
Adults
Male
13.5 - 17.5 g/dL
Female
12.0 - 15.5 g/dL
Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088
Children
Newborn
14 - 24 g/dL
Infant
9.5 – 13 g/dL
Pregnancy
11 – 12 g/dL
77% HbF (Newborn)
↓
23% HbF (after 4 month)

Hemoglobin Synthesis
Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088
a and β genes
mRNAs
a and β globins chain
Haemoglobin
Succinyl CoA+ Glycine
Protophophyrins
Heme
Fe

Erythropoiesis
Primitive Hemopoietic Stem Cell (HSC)
Proerythroblast
Early normoblast
Late normoblast
Reticulocyte
Erythrocyte

Regulators of Erythropoiesis
• Erythropoietin (EPO)
Synthesis depends on the supply of
1. Iron
2. Folic Acid
3. Vitamin B12
Binds O2 in the Hb within PBC
For Thymine synthesis  DNA formation 
Normal cell division/maturation
Deficiency 
↓Hb Production 
↓Erythropoiesis
Stimulate proliferation of erythrocytes progenitor
cells & their differentiation into mature RBCs
Required for Folic acid function  DNA formation
 Normal cell division, maturation

The Pathology: ANEMIA
By Group 1

Anaemia
Definition
WHO : ANAEMIA is a condition in which the number of
red blood cells or their oxygen carrying capacity is
insufficient to meet physiologic needs, which vary by
age, sex, altitude, smoking and pregnancy status.
OXFORD : ANAEMIA is defined as low heamoglobin
(Hb) concentration, and may be due either to a low red
cell mass or increased plasma volume.
Source : www.who.int/topics/anaemia/en/

Reduction of Hb concentration below
normal
ANAEMIA
Female Adult : <11.5 g/dL
Male Adult : < 13.5 g/dL
2 years – puberty : < 11 g/dL
Newborn infants : < 14 g/dL

Types of Anemia
Based on Mean Cell Volume (MCV)
- Normal MCV : 76-96 fL (femtolitres)
Low MCV
MICROCYTIC
ANAEMIA
Normal MCV
NORMOCYTIC
ANAEMIA
High MCV
MACROCYTIC
ANAEMIA
Varying MCV
HAEMOLYTIC ANAEMIA

Low MCV
MCV < 80fL
MCH <27pg
MICROCYTIC
ANAEMIA
Normal MCV
MCV 80 – 95 Fl
MCH > 27 pg
NORMOCYTIC
ANAEMIA
High MCV
MCV > 95 fL
MACROCYTIC
ANAEMIA
1. Iron-Deficiency
Anaemia
2. Thalassemia
3. Sideroblastic
Anaemia
1. Acute blood
loss
2. Anaemia of
Chronic Disease
3. Bone marrow
failure
4. Renal failure
5. Hypothyroidism
6. Haemolysis
7. Pregnancy
1. B12 / Folate
Deficiency
2. Alcohol excess /
Liver Disease
3. Reticulocytosis
4. Cytotoxics
5. Marrow
infiltration
6. Hypothyroidism
7. Antifolate drugs
(Phenytoin)
Source : Murray Longmore, Oxford Handbook of Clinical Medicine, 9th Edition, 2014.
MCV: 80 to 100fL
MCH: 27 to 31
picograms/cell.

CLASSICAL SIGN AND SYMPTOMS
SIGNS SYMPTOMS
Pallor Shortness of breath
Tachycardia (Compensatory Mechanism) Lethargic
Cardiac failure Weakness
Palpitation
Headaches
Angina pectoris
Confusion

Iron Deficiency Anemia (IDA)
Group 3

• Most common and widespread of nutritional disorder in the world
• Affecting large number of women and children in non-industrialized
country and virtually all industrialized nations.
• Half of pregnant women in the world estimated to be anemic (52% non
industrialized, 23% industrialized.)
Prevalence

Classification
based on WHO
Malay
N=135
Chinese
N=130
Indian
N=123
All
N=388
Anemia
(Hb < 12g/L)
16.4 20.6 26.4 20.9
Depleted iron
storage (ferritin <15
22.9 25.2 53.9 33.0
IDA
(Hb<12g/L+ferritin
<15 + MCV <80 fl
4.3 9.9 18.0 10.3
The prevalence of anaemia and IDA
among urban Malaysian women
Prevalence of anaemia, depleted iron stores and IDA
(Medicine UPM 2010)

WHO regions Children
(0-4years)
Children
(5- 14 years)
Pregnant
women
All
women
(15-
59years)
Men
(15-
59years)
Elderly
Africa 45 228 85 212 10 800 57 780 41 925 13 435
America 14 220 40 633 4 500 53 787 19 443 12 617
South East Asia 111 426 207 802 24 800 214 991 184 752 60 206
Europe 12 475 12 867 2 400 27 119 13 318 18 095
Eastern
mediteranian
33 264 37 931 7 700 60 196 41 462 11 463
Western pacific 29 793 156 839 9 700 158 667 174 400 78 211
Overall 245 386 541 284 59 900 572 540 475 300 194 029
Estimated prevalence of anaemia (1990-1995) by WHO Region based on
blood haemoglobin concentration (WHO)

Mariah a 17 year old student who has recently migrated from Australia to
Malta with her parents. She comes to you complaining of general fatigue and
occasional dizziness. Mariah has no significant past medical history and is not
any regular medicine. She does not drink alcohol or smoke. Her parents are
both healthy. On examination, she has strong peripheral pulses, and her
cardiovascular system examination is normal. BP is 115/75mmHg, pulse
90/min and BMI 19.5kg/m2. Mariah has pale skin, conjunctiva and nail beds.
Scenario

Poor Diet
Intake
Pathophysiology& Causes of IDA
Loss Of IRON Stores (Depletion
Of Hemoglobin Recourse)
Malabsorption
Increased
demands
Chronic blood
loss

• GIT : peptic ulcer, esophageal varices, aspirin ingestion,
stomach/caecum/colon carcinoma, hookworm, angiodysplasia etc.
• Uterine menstrual loss (Menorrhagia)
• Prolonged hematuria, hemoglobinuria,, pulmonary haemosiderosis ,self
inflicted blood loss (rare)
Chronic blood loss

• Prematurity
• Growth
• Pregnancy
• Erythropoietin therapy
Increased demands

• Gluten-induced enteropathy
• Gastrectomy
• Autoimmune (atrophic) gastritis
Malabsoprtion

• A major factor in many developing countries but rarely the sole cause in
developed country
Poor diet intake

• Brittle nails
• Koilonychia
• Atrophy of papillae of the tongue, painless glossitis
• Angular stomatitis
• Dysphagia ( Plummer Vinson syndrome)
• Pica
Sign and Symptoms of IDA

• Blood count and film
- microcytic (MCV< 80 fl) and hypochromic (MCH < 27pg) anemia
- Poilocytosis
- Anisocytosis
Investigation
Iron deficiency anemia, severe. Blood film.
The field displays virtually all hypochromic
cells with an exaggerated pale center (arrow)

Test Findings
MCV Reduced
Serum iron Reduced
Serum TIBC Raised
Serum ferritin Reduced
Serum soluble transfer receptor Increased
Iron in marrow Absent
Iron in erythroblast Absent
Investigation cont.

• Treat the underlying causes
• Oral iron – ferrous sulphate ( 200mg three times daily, a total of 180mg
ferrous iron ) /- ferrous gluconate (300mg twice daily , only 70mg ferrous
iron)
• Parenteral iron (for high iron requirement)– ferric hydroxide sucrose (
200mg )/ iron dextran/ ferric carboxymaltose
Management

DEFINITION & EPIDEMIOLOGY
DEFINITION
Hereditary disease (autosomal recessive) ;
Defective in synthesis of globin chain in thalassemia -> imbalance globin
chain production-> precipitation of globin chain within red cell precursor->
ineffective erythropoiesis.

CAUSES
 Thalassemia is caused by
mutations in the DNA of cells that
make hemoglobin .
 The mutations associated with
thalassemia are passed from
parents to children.
 The mutations that cause
thalassemia disrupt the normal
production of hemoglobin and
cause low hemoglobin levels and a
high rate of red blood cell
destruction, causing anemia.

CLASSIFICATION
thalassemia
alpha
1 gene
deletion
2 gene
deletion
3 gene
deletion
4 gene
deletion
beta
major minor Intermedia

CASE SCENARIO
Adriana is a 7 –years-old who lives with her parents in a suburban community.
Her parents brought Adriana to the US from their homeland in Greece when
she was 1-year-old. At the age of 3, Adriana was in the 10th percentile for
height and weight, pale, and her Hb was 5.8 g/dl. Following further diagnostic
studies, she was diagnosed with beta thalassemia major. Over the cause of the
next 4 years, Adriana was hospitalized every 1 – 2 months, so she could be
transfused with pack red blood cell.

PATHOPHYSIOLOGY
• α-thalassemia
 primarily to gene deletion causing reduced α-globin chain synthesis
 Since all adult haemoglobin are containing, α-thalassemia produces no change in
the percentage distribution of haemoglobin A, A2 and F. In severe form of α-
thalassemia, excess β chain may form a β4 tetramere called haemoglobin H.
• β-thalassemia
Defects that result in absent β globin chain is called as βᴼ
Reduced synthesis is termed β

SIGNS AND SYMPTOMS
TYPES ( ALPHA THALASSEMIA) SIGNS AND SYMPTOMS
Four-gene deletion (Hb Barts) Pale, oedematous, enormous livers and
spleen (hydrops fetalis)
Three-gene deletion Moderate anaemia and splenomegally
Two-gene deletion Mild anaemia
One-gene deletion Normal

TYPES ( BETA THALASSEMIA) SIGN AND SYMPTOM
Thalassemia minor Anaemia is mild or absent
Thalaasemia intermedia -Moderate anaemia
- May varies depending on mutation
Thalassemia major -severe anaemia
-Failure to thrive
-recurrent bacteria infection
-hepatosplenomegaly
-bone expansion
-classical thalassemic facies
-jaundice

INVESTIGATIONS (Can Be Applied To
Both Alpha & Beta)
• Complete blood count
– Hb, MCV, MCH low
– RBC increased
– Red cell distribution width (RDW) – normal
• Peripheral blood film
– Microcytic, hypochromic
– Target cells, basophilic stipling, ± nucleated RBC
Blood smear showing
marked microcytosis,
hypochromia, target
cell, and anisocytosis.
Peripheral blood smear
showing basophilic
stippling

CONT
• Hb analysis
– HPLC – No Hb A at all, replaced by Hb F and A2
– Hb electrophoresis – will be further explain after
this
• DNA analysis – alpha and/or beta gene
• Family screening

CONT…
•Haemoglobin (Hb) electrophoresis test
• Blood test done to check the different types of Hb in the blood.
• It uses an electrical current to separate normal and abnormal types of Hb in the
blood. Hb types have different electrical charges and move at different speeds.
The amount of each Hb type in the current is measured.
• An abnormal amount of normal Hb or an abnormal type of Hb in the blood may
mean that a disease is present.
• Typical finding : HbA decreased or absent, HbF increase, HbA2 variable

CONT…
• The most common abnormal Hb are :
– Haemoglobin S. This type of haemoglobin is present in sickle cell
disease.
– Haemoglobin C. This type of haemoglobin does not carry oxygen
well.
– Haemoglobin E. This type of haemoglobin is found in people of
Southeast Asian descent.
– Haemoglobin D. This type of haemoglobin is present in some sickle
cell disorders.

COMPLICATIONS
•Iron overload.
 People with thalassemia can get too much iron in their bodies, either from the disease
itself or from frequent blood transfusions.
 Too much iron can result in damage to :
•Infection.
 People with thalassemia have an
increased risk of infection,
especially to those who had
splenectomy.

• In cases of severe thalassemia:
• Bone deformities.
 Thalassemia can make bone marrow expand, which causes bones to
widen.
 This can result in abnormal bone structure, especially in face and skull.
 Bone marrow expansion also makes bones thin and brittle, increasing
the chance of broken bones.
•Enlarged spleen (splenomegaly).
 Thalassemia is often accompanied by the destruction of a large number
of red blood cells, making spleen work harder than normal, causing it
to enlarge.
 Splenomegaly worsen anemia as it can reduce the life of transfused red
blood cells.
 If spleen grows too big, it may need to be removed.

•Slowed growth rates.
 Anemia can cause a child's growth to slow.
 Puberty also may be delayed in children with thalassemia.
•Heart problems.
 Heart problems, such as congestive heart failure and abnormal heart rhythms
(arrhythmias), may be associated with severe thalassemia.

Aetiology (Hereditary)
Structural defect of ALA-S
gene
Impairment of heme synthesis
Accumulation of iron in
mitochondria of erythroblasts
A ring of iron granules seen in
Perls’ stain

Aetiology (Acquired)
Malignant
diseases
Benign conditions

Signs & Symptoms
•Shortness of breath
•Weakness
•Lethargy
•Palpitation
•Headaches
•Visual disturbances – due to retinal
haemorrhages
•In older pt , symptoms of cardiac
failure , angina pectoris or
intermittent claudication or
confusion may be present.
•Pallor of mucous membranes
•Tachycardia
•Bounding pulse
•Systolic flow murmur at apex
SignsSymptoms

Laboratory investigations
Full blood
count
Red cell
indices
Peripheral
blood film
Bone
marrow iron
Iron studies

*Presence of 15% or more of ring
sideroblasts in bone marrow
Basophilic stippling seen in lead poisoning

Sideroblastic anaemia
Hb Low
MCV Usually low in congenital type but MCV
often raised in acquired type
MCH Usually low
Serum iron Raised
TIBC Normal
Serum transferrin receptor Normal
Serum ferritin Raised
Bone marrow iron stores Present
Erythroblast iron Ring forms
Haemoglobin electrophoresis Normal

Management
Pyridoxine
therapy
Removal of toxic
agents
Folic acid therapy
Blood transfusion
+ iron chelating
agent

• Other factors that have been implicated:
– Bone marrow toxins retained in renal failure
– BM fibrosis secondary to hyperthyroidism
– Haematinic deficiency– iron, vit B12, olate
– ↑ red cell distribution
– Abnormal red cell membranes causing ↑ osmotics
fragility.
– ↑ blood loss– occult GIT bleeding, blood
sampling, blood loss during haemodialysis or b’coz
of platelet dysf(x).
– ACE inhibitors(by interfering w control of
edogenous erythropoietin release)
11/18/2015

Epidemiology
• In developing countries, the deficiency of vitamin B12 is
significant in Africa, India, and South and Central America
due to low intakes of animal products.
• In western countries, severe deficiency is usually caused by
pernicious anaemia.
• B12 deficiency is more common in the elderly because B12
absorption decreases in atrophic gastritis patients which is
common in the elderly.

Case Scenario
A 70-year-old woman presented with progressive weakness and fatigue.
The symptoms had begun about a month earlier, and she no longer felt well
enough to do her housework or take her daily walk. She experienced shortness
of breath on exertion. Complete blood cell count (CBC) was performed and the
results were, hemoglobin, 5.4 gm/dL; mean corpuscular volume (MCV), 103
µm3 (normal 76-96) ; red cell distribution width (RDW), 19.8% (normal, 12%-
15%),
She had no history of recent bleeding, jaundice, fever, anemia, or heart
disease. She had not been exposed to medications (other than occasional
vitamins and aspirin) or toxins.. Findings on the physical examination were
unremarkable except for mild tachycardia at rest (96 bpm), a blood pressure of
146/84 mm Hg recumbent and 142/78 mm Hg standing, pallor. Neither the liver
nor spleen were palpable. The stool was negative for occult blood. A chest x-ray
was normal, and an electrocardiogram showed only sinus tachycardia. The
blood urea nitrogen (BUN) level was 15 mg/dL; glucose, 108 mg/dL; and total
bilirubin, 1.2 mg/dL (normal, <1.2). Electrolyte levels were normal. A sickle
cell preparation was negative. Low serum B12 was notedBlood Film was
ordered

Causes of Megaloblastic Anaemias
• Vitamin B12 deficiency
• Folate deficiency
• Abnormalities of vitamin B12 or folate
metabolism (eg transcobalamine deficiency ,
nitrous oxide, antifolate drugs)

Pathophysiology of Vitamin B12
Vitamin B12 is cofactor for:
1) Synthesis of thymidine
2) Normal methionine synthesis
In their absence:
Cause inadequate DNA synthesis
Defective nuclear maturation
(Nucleocytoplasmic Ansynchrony)
Blockade in cell division
Leads to:
• Abnormal large RBCs and erythroid precursors (megaloblasts).
• Affect granulocyte maturation.
• Neurologic complication:- attribute to abnormal myelin degradation.

Vitamin B12 Deficiency
Causes of severe vitamin B12 deficiency
1. Nutritional
– Inadequate intake
– Vegetarianism
2. Malabsorption
– Gastric causes
– Pernicious anemia
– Congenital lack or abnormality of IF
– Total or partial gastrectomy
– Intestinal causes: chronic tropical sprue, intestinal stagnant loop
syndrome, ileal resection, Crohn’s disease, fish tapeworm

Causes of mild vitamin B12 deficiency
• Malabsorption of B12
• Elderly
• Atrophic gastritis
• Severe pancreatitis
• Gluten induced enteropathy
• HIV infection or therapy with metformin

Pathophysiology of Folate
• Folate enter plasma as methyl THF.
• Methyl THF is a required in synthesis of
thymidine thus, for DNA synthesis.
• Lack of folate cause :
– Inadequate DNA synthesis thus, abnormal large
RBC synthesis.

Folate Deficiency
Causes of folate deficiency
• Nutritional
– Especially old age, institutions, poverty, famine, special diets
• Malabsorption
– Tropical sprue, gluten induced enteropathy, partial gastrectomy, extensive jejunal resection or
Crohn’s disease
• Excess urinary folate loss
– Active liver disease, CCF
• Drugs
– Anticonvulsants, sulfasalazine
• Excess utilization
– Physiological
• Pregnancy, lactation, prematurity
– Pathological
• Haematological disease (haemolytic anaemias, myelofibrosis)
• Malignant disease: carcinoma, lymphoma, myeloma
• Inflammatory diseases: Crohn’s disease, tb , RA, psoriasis, malaria
• Mixed
– Liver disease, alcoholism, ICU

Clinical Features
• Onset – insidious/ gradually progressive sign and
symptoms of anemia
• Mildly jaundice- excess breakdown of hb due to
increase ineffective erythropoiesis
• Glossitis, angular stomatitis, mild symptoms of
malabsorption with loss of weight
• Neuropathy (severe B12 deficiency)
• Neural tube defect in fetus (eg : encephaly, spina
bifida)
• Increased melanin pigmentation

Glossitis : beefy-red and painful tongue
Angular stomatitis
Baby with neural tube defect (spina bifida)
From : Essential Haematology , 6th Edition

Investigation
• FBC: MCV > 98fL
• FBP : Oval macrocytic rbcs, hypersegmented neutrophils, pancytopenia
• BMA : hypercellular, large erythroblast, failure of nuclear maturation, giant
metamyelocytes (BMA is not mandatory in B12/folate deficiency)
• Increased serum unconjugated bilirubin, LDH
• Reduced serum/ red cell folate and B12 (mandatory test)

Treatment of Megaloblastic Anaemia
Vitamin B12 deficiency Folate deficiency
Compound Hydroxocobalamin (B12) Folic acid
Route Intramuscular Oral
Dose 1000ug 5mg
Initial dose 6x1000ug over 2-3 weeks Daily for 4 months
Maintenance 1000ug every 3 months Depend on underlying
disease; lifelong theraphy
may be needed in chronic
inherited haemolytic
anaemias, myelofibrosis,
renal dialysis
Prophylactic Treatment
Given To:
Total gastrectomy
Ileal resection
Pregnancy, severe
haemolytic anaemias,
dialysis, prematurity

Normochromic & Normocytic
Anemia
Group 1

Acute of Chronic Disease (ACD)
• Common type of anaemia among pt with chronic inflammatory and malignant dz
• Causes of ACD :
– Chronic iflammatory disease
• Infections (pulmonary abcess, tb, osteomyelitis, pneumonia)
• Non infectious (RA, SE, CTD, sarcoidosis )
– Malignant disease ( ca, lymphoma, sarcoma )
• Sign and symptoms depends on underlying causes
• Not related to bleeding, haemolysis or marrow infiltration
• EPIDEMIOLOGY
 Most common anemia amongst patients with chronic inflammatory and
malignant disease.
 2nd commonest anemia after IDA, worldwide.

CASE SCENARIO 1
A 72 - year – old man, previously healthy, presents with fever, chills, cough
and SOB. CXR shows a right – middle – lobe infiltrate. He is diagnosed
with pneumonia and admitted for iv antibiotics. Blood cultures
eventually grow Strep. Pneumoniae. By hospital day 3, he is afebrile but his
Hb is 10.5 g/dl, down from 12.4 g/dl on admission and 13.5 g/ dl 1 month
ago. He has no evidence of GI blood loss or overt haemolysis. Red cell indices
revealed a normocytic normochromic anaemia.

CHARACTERISTIC FEATURES
Anemia in chronic disease
MCV/MCH Normochromic normocytic anaemia or mildly
hypochromic (MCV rarely <75fL)
Serum iron Reduced
TIBC Reduced
Serum ferritin Normal/ raised
Bone marrow iron stores Present
Eryhtroblast iron Absent
Hb electropheresis Normal

• Pathogenesis-
 Key regulatory protein – hepcidin which is produced by liver
 High levels of production are encouraged by pro-inflammatory cytokines,
especially IL- 6.
 Hepcidin binds to ferroportin on the membrane of iron exporting cells, and
thereby inhibiting the export of iron from these cells into the blood
Iron remain trapped inside the cells in the form of ferritin, levels of which
are therefore normal or high in the face of significant anaemia
• Treatment- treat underlying cause (eg. 60% RA patients).
• Inhibition hepcidin and inflammatory modulator → block the inhibition of iron
transfer.

EXAMPLE- ANEMIA IN CHRONIC KIDNEY
DISEASE(CKD)
• Anaemia is a complication of CKD whereby
erythropoietin deficiency is the most significant
cause.
• Insufficient or absent erythropoietin secretion results
in normochromic, normocytic anaemia.
• The anaemia becomes more severe as the
glomerular filtration rate progressively decreases.

Haemolytic Anaemia
HERIDATARY ACQUIRED

Loss Of Elasticity:Sickle Cell
Anaemia
o Sickle cell disease is a group of haemoglobin disorder in which the
sickle β-globin gene is inherited.
o Homozygous sickle cell anaemia (Hb SS) is the MOST COMMON
o Doubly the doubly heterozygote conditions if Hb SC and Hb
Sβthal also cause sickling disease
o The abnormal red blood cells are rigid and crescent- like shaped
that can stuck in the blood vessels resulting in blocking of the
blood flow. Hence, distribution of the blood to supply oxygen to
all parts of the body might be impaired.
Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 85).

Epidemiology
o It is believed that the sickle cell abnormal hemoglobin originated in
Africa, where it is most commonly encountered, while India is
considered as an additional place of origin. HbS is prevalent in
Middle East and Mediterranean countries, while population migration
has taken the gene to almost all regions of the world, including
Western and Northern Europe.
o About 7% of the global population carry non-functional hemoglobin
gene, with more than 500 000 affected children born annually. More
than 80% of these are born and live in the developing countries in the
world.
o More than 70% of them have a sickle disorder. A number of affected
children born in developing countries might be died, misdiagnosed,
receiving treatment or left untreated.

Causes
Point mutation at 6th codon of β globin (Glutamate  valine)

Clinical Features
1. Vaso-occlusive crises
The earliest presentation in the first few years of life is acute pain in
hand, and feet (dactylitis) dt vaso-occlusion of the small vessels.
Severe pain in the other bones occur in older children/adult. Fever often
accompanies the pain.
2. Anaemia
Hb range from 6-8 g/dL but acute fall in Hb level can occur owing
to :
• Splenic sequestration
• Bone marrow aplasia
• Further haemolysis
Kumar, P. (n.d.). Kumar & Clark’s clinical medicine
(Seventh ed., p. 409, 410)

3. Splenic Sequestration
• Vaso-occlusion causes acute painful enlargement of the spleen
• Causing splenic pooling of RBC  hypovolaemia  circulatory
collapse  death
4. Aplastic Crises
Caused by infection with Parvovirus B19 or Folate deficiency
Clinical Features (cont)

Long-term Complications
• AFFECT GROWTH AND DEVELOPMENT OF CHILD
– Short statue in young children (regain height by adulthood)
– weight not appropriate with age (below normal weight)
– Delayed sexual maturation (boy- no increase in testicular volume
by 14 years; girl- no breast development by 13 and a half years)
• BONE
– Common site for vaso-occlusive of small vessels.
• Avascular necrosis of hips and shoulders
• Compression of vertebrae
• Shortening of bones in the hands and feet.
• Osteomyelitis (by Staphylococcus aureus, Staphylococcus
pneumoniae, Salmonella)

INFECTIONS
• Tissue susceptible to vaso-occlusive (Bones , lungs, kidneys)
LEG ULCERS
• Occur spontaneously (vaso-occlusive) or following trauma. Then become
infected and resistant to treatment.
CARDIAC PROBLEMS
• Cardiomegaly, arrthymias, iron overload cardiomyopathy.
• Myocardial infarction due to thrombotic episodes.
NEUROLOGICAL COMPLICATIONS
• 25% of patient
• Transient ischemic attacks, fits, cerebral infarction, cerebral haemorrhage,
coma.
• Strokes occur in about 11% of patient under 20 years of age.
• Most common finding is obstrustion of a distal intracranial internal carotid
artery or a proximal middle cerebral artery.

Cholelithiasis
– Pigment stone as a result of chronic haemolysis
Liver problems
– Chronic hepatomegaly and liver dysfuction caused by trapping of sickle cells.
Renal. Chronic tubulointestitial nephritis.
Priapism.
– Unwanted painful erection as a result of vaso-acclusion.
– Impotence
Eye
– Background retinopathy, proliferative retinopathy, vitreous haemorrhages and retinal
detachment all occur
Pregnancy
– Impaired placental blood flow causes
• Spontaneous abortion
• Intrauterine growth impairment
• Pre-eclampsia
• Fetal death

Investigations
1. Complete blood count (CBC)
Anaemia (Hb range 6-8 g/dL)
High reticulocyte count (10-20%)
2. Blood films (feature of hyposplenic
and sickling
Sickle cells(arrowed) and
target cells.
Post splenectomy film with Howell-Jolly
bodies(arrowed), target cells and irregular
contracted cells.
(Seventh ed., p. 410)

Investigations (cont)
3. Sickle solubility test
A mixture of HbS in a reducing solution
(sodium dithionite) gives a turbid apperance
because of precipitation of HbS
Normal Hb gives clear solution
5. The parents of the affected child will
show features of sickle cell trait.
Normal
Sickle cell trait
Sickle cell anaemia
Hb electrophoresis
4. Hb electrophoresis to confirm
diagnosis
Results shows : no Hb A, 80-95% Hb SS,
and 2-20% Hb F

Treatment
o Prophylactic –to avoid those factors known to precipitate crises, esp dehydration,
anoxia, infections, stasis to the circulation and cooling of the cell surface
o Folic acid (5 mg once weekly)
o Pneumococcal, haemophilus, and meningococcal vaccination and Hepatitis B
vaccine if transfusion is needed.
o Regular oral penicillin (should start at dx and continue at least until puberty)
o Crises –treat by rest, warmth, rehydration by oral fluid and/or IV normal saline
(3L in 24H)
–blood transfusion is given in severe anaemia
o Hydroxyurea (15-20 mg/kg) can increase Hb F levels and have shown to improve
the clinical course children/adults who are having 3 or more painful crises each
year
o For pain –analgesia at appropriate level should be given (NSAID, opiates or
paracetamol)
Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 89).

1. Membrane defects : Hereditary
Spherocytosis
• Most common in northern Europeans
Pathogenesis :-
• Vertical interactions between the membrane skeleton and the
lipid bilayer of the red cell
• Loss of membrane because release of parts of the lipid bilayer
that are not supported by the skeleton
• Normal biconcave red cell but become increasingly spherical
as loss of surface area relative to volume as they circulate
through spleen and the rest of RE system
• Unable to pass through splenic microcirculation where they
die prematurely

Membrane defects : Hereditary
Spherocytosis
Molecular basis :-
• Ankyrin deficiency/ abnormalities
• Alpha or beta – spectrin deficiency / abnormalities
• Band 3 abnormalities
• Pallidin (protein 4.2) abnormalities

Clinical features :-
• Autosomal dominant rarely recessive
• Anemia can be present at any age
• Fluctuating jaundice (particularly marked if a/w Gilbert’s disease (a defect
of hepatic conjugation of bilirubin) ; splenomegaly occurs in most patients
• Frequent pigment gallstones
Membrane defects : Hereditary Spherocytosis

Investigation :-
• A rapid fluorescent flow analysis of eosin-maleimide bound to red cells
• Treatment :-
• Splenectomy : preferably laparoscopic but only if clinically indicated
;symptomatic anemia/gallstones/leg ulcers/growth retardation – risk of
post-splenectomy sepsis particularly in early childhood
• Cholecystectomy should be performed with splenectomy if symptomatic
gallstones are present
Membrane defects : Hereditary
Spherocytosis

2. Defective red cell metabolism : Glucose-
6-phosphate dehydrogenase deficiency
Epidemiology :-
• 400 million people worldwide are deficient in enzyme activity
• Sex-linked
• Affecting males
• Carried by females (advantage resitance to Falciparum Malaria
• Main races :- West Africa, the Mediterranean, the Middle East and SE Asia
• Mildly in black Africans, more severe in Orientals and most severe in Mediterranean
• Severe deficiency occurs occasionally in white people

Agents that may cause HA in G6PD deficiency (Things that induce
OXIDATIVE STRESS) :-
• Infections and other acute illnesses eg DKA
• Drugs – antimalarials eg primaquine, sulphonamides eg cotrimoxazole,
analgesics eg aspirin, antihelminths eg beta-napthol
• Fava beans or other vegetables
• Miscellaneous eg vit K analogues
Defective red cell metabolism : Glucose-6-
phosphate dehydrogenase deficiency

Pathogenesis :-
• Function of G6PD is to reduce nicotinamide adenine dinucleotide
phosphate (NADP)
• The only source of NADPH for production of glutathione
• Defieciency of G6PD renders the red cell susceptible to oxidant stress
• Most common types are B (Western) and type A in Africans

Clinical features :-
• Usually asymptomatic
• Main syndromes :-
1. Acute HA in response to oxidant stress eg drugs, fava beans or infections –
caused by rapidly developing intravascular haemolysis with
haemoglobinuria, the anemia maybe self limiting as new young red cells
are made with near normal enzyme levels
2. Neonatal jaundice
3. Rarely, a congenital non-spherocytic haemolytic anemia
These syndromes may result from different types of severe enzyme deficiency

Diagnosis :-
• Between crises the blood count is normal
• By screening test or direct enzyme assay on red cells
• During crises – ‘bite’ cells/ ‘blister’ cells / contracted and fragmented cells
which have had Heinz bodies removed by the spleen. Heinz bodies are
oxidized, denatured Hb
• Higher enzyme level in young red cells, red cell enzyme assay may give a
‘false’ normal level in the phase of acute hemolysis with a reticulocyte response
• Subsequent assay after the acute phase reveals the low G6PD level when the
red cell population is of normal age distribution

Treatment :-
• Stop offending drugs
• Treat underlying infection
• Maintain high urine output
• Blood transfusion for severe anemia when necessary
• Photography and exchange transfusion might be needed in severe cases
for neonates as they are prone to neonatal jaundice. The jaundice is
usually not caused by excess haemolysis but by deficiency of G6PD
affecting neonatal liver function
Defective red cell metabolism :
Glucose-6-phosphate dehydrogenase
deficiency

Haemolytic Anaemia
HERIDATARY ACQUIRED
Group 4

A 32-year-old man gradually noticed that he had yellow eyes and
dark urine, felt continually tired, and was short of breath when
climbing stairs.
He had no other symptoms; in particular there was no itching,
fever or bleeding, and he was not taking any drugs. On
examination, he was anaemic and jaundiced.
He was afebrile and had no palpable lymphadenopathy, but
evident of splenomegaly

Possible Diagnosis?
Possible causes Points
Liver disease Jaundice
Dark urine
Splenomegaly
Hemolytic anemia Jaundice
Dark urine
Shortness of breath
Tired
Splenomegaly

INVESTIGATION
FBC
• Haemoglobin 54g/l (130- 180 g/l)
• WBC 9.4 x 109/L
• Platelets 192 x 109/L
• MCV 120 fl (76-96 fl)
• Reticulocyte count 9% (<2%)
• The blood film shows gross polychromasia and spherocytes; Suspected :
Hereditary spherocytosis
AIHA

FURTHER INVESTIGATION
• LFTs
Serum bilirubin 47 umol/L ( 3-17umol/L)
• LDH 5721 iu/L (105-333iu/L)
• DAT 3+ positive with IgG
.

PROVISIONAL DIAGNOSIS
Warm AIHA  +ve DAT with IgG

Autoimmune hemolytic anemia
• Acquired disorder resulting from increased red cell destruction d/t
red cell autoantibodies.
• Classification :
• Warm AIHA
• Cold AIHA
• Paroxysmal cold haemoglobinuria (PNH)

Warm AIHA
• Autoantibodies predominantly IgG
• Possess relatively high affinity for RBCs at 37ºc
• Clinical Features
• Occur at any age either sex
• Short episode of anemia and jaundice.
• Generalised symptoms –fatigue, weakness, malaise, fever
• Splenomegaly & hepatomegaly common

Cold AIHA
Autoimmune predominantly IgM
Antibody attach to red cells and cause agglutination – at lower
temperature <4◦C
• Infection related : Mycoplasma. pneumonia, EBV
• Clinical Features
• Exacerbation in winter
• Cold, painful, often blue fingers, toes, ears or nose (Acrocynosis)

Paroxysmal cold haemoglobinuria (PNH)
• Due to a biphase IgG antibodyAttaches with complement to RCs
in the cold extremities
• Causes lysis when the cell is warmed later from the complement
which remains attached
• Post-viral phenomenon
• Typically an acute self-limiting disease

Clinical features PCH
• Presents acutely with leg and back pain, abdominal pain with
cramps, nausea/vomiting/diarrhoea and
• dark urine (haemoglobinuria)
• following exposure to the cold

Investigation for suspected AIHA
• FBC and reticulocyte count
• Blood film
• DAT (Direct Agglutination Test)
• Donath Landsteiner Ab (test for PNH)
• Blood group specificity
• Cold agglutinin titre
• Tests for associated infection or disease

Treatment
• Corticosteroid (induced remission)
• Splenectomy (if fail to respond well to corticosteroid)
• Immunosuppressive drugs ( rituximab)
• Blood transfusion (if necessary)
• Avoidance of Cold ( Cold AIHA & PNH)
• Folic acid – as active hemolysis consume folate

Classification
(source : Essential Haematology Hoffbrand Moss)
Induced by red cell
antigens
• Haemolytic
transfusion
reactions
• Haemolytic disease
of the newborn
• Post stem cell grafts
Drug-induced
• Drug-red cell
membrane complex
• Immune complex

Haemolytic transfusion reactions
Immediate Delayed

Clinical features of a major haemolytic
transfusion reaction
Haemolytic
shock phase
Oliguric phase
Diuretic
phase

Investigations
Check for blood
compatibility and
bacterial
contamination of
the blood

Management
To maintain
blood
pressure and
renal
perfusion
IV dextran,
plasma or
saline &
frusemide
IV
hydrocortisone
&
antihistamine
IV adrenaline
Compatible
transfusion

Drug-induced immune
haemolytic anemia

Drug-induced immune haemolytic
anemia
• Drug-induced immune hemolytic anemia is a blood
disorder that occurs when a medicine triggers the body's
defense (immune) system to attack its own red blood cells.
• Drugs can cause HA by 3 mechanisms.
1)Antibody directed against a drug red-red cell membrane
complex – Penicillin, ampicillin
2)Deposition of complement via a drug protein(antigen)-
antibody complex onto the red cell surface – Quinidine,
Rifampicin
3)A true autoimmune hemolytic anemia with unclear role of
the drug – methyldopa

Symptoms
• Dark urine
• Fatigue
• Pale skin color
• Rapid heart rate
• Shortness of breath
• Yellow skin color (jaundice)
Investigations
Physical examination : enlarged spleen
Tests : blood/ urine test
- Absolute reticulocyte count
- Direct or indirect Coombs test
- Indirect bilirubin levels
- Red blood cell count
- Serum haptoglobin
Treatment
- Stop taking the drugs
-Take a prednisone to suppress
the immune response against
the red blood cells. Special
blood transfusions may be
needed to treat severe
symptoms.

Red Cell Fragmentation syndromes.
DEFINITION
• Form of haemolytic anaemia caused by intravascular m
echanical trauma resulting in destruction of red cells, re
lated to cardiovascular defects and haemolytic anaemia.
• Caused by red blood cells passing through abnormal
small vessels with also fibrin deposition.
• Also known as microangiopathic hemolytic anemia.
• Also associated with disseminated intravascular
coagulation or platelet adherence.

Infection-induced hemolytic anemia
Microorganisms may cause injury to red cells through different
mechanisms such as:
(1) physical invasion of red cells (e.g. malaria)
(2) hemolysin secretions(alpha toxin) to damage the red cells directly
(e.g. Clostridium perfringen)
(3) infection that triggers formation of antibody (anti-I) against red
cells (e.g. mycoplasma)
(4) microangiopathic hemolysis caused by disseminated intravascular
coagulation associated with infection.
(5) may precipitate haemolytic crisis in G6PD deficiency.

Anaemia in
infant & children
PAEDIATRICS TEAM:
Muhammad Faiz Bin Nordin
Bibi Afzarina Binti Mohamed Hanafee
Hanis Zahirah Binti Baharudin

Definition
Anaemia is defined as an Hb level below the
normal range.
The normal range varies with age, so anemia can
be defined as:
• Neonate : Hb < 14 g/dl
• 1-12 months : Hb < 10 g/dl
• 1-12 years : Hb < 11 g/dl

Causes of anaemia in infant & children
• Impaired red cell production
• Increased red cell destruction (haemolysis)
• Blood loss
• Anaemia of prematurity

Impaired red cell production
May be due to
Infective erythropoiesis
- iron deficiency
red cell aplasia
- Fanconi anemia

Infective erythropoiesis:
Iron deficiency
• Main cause
- inadequate intake
- malabsorption
- blood loss
• Common in infants because additional iron is
required for ↑ blood volume accompanying
growth & to build up

• Diagnostic clue for infective erythropoiesis
- normal reticulocyte count
- abnormal MCV of RBC :
*low in iron deficiency
*raised in folic acid deficiency

• Iron may come from
- breast milk
*low iron content but 50% of iron is absorbed
- infant formula: supplement
- cow’s milk
*higher iron content than breast milk but only
10% is absorbed.
- solid introduced at weaning

Iron requirement
during childhood

• Clinical feature
- most infant & children are asymptomatic
until Hb drop below 6-7 g/dl
- When it become worsen, children tire easily
& young infant feed more slowly than usual.
- appear pale but pallor is an unreliable sign
unless confirmed by pallor of conjuctiva, tongue
or palmar creases.
- children have ‘pica’

• Management
- dietary advice and supplementation with oral
iron.
*except for malabsorption (celiac disease) & chronic
blood loss patient (Meckel diverticulum)
- should be continue until Hb is normal and then
for a minimum of a further 3 months to
replenish the iron stores.
- Blood transfusion should never be necessary for
dietary IDA

Red cell aplasia
• Causes
- congenital red cell aplasia
*Fanconi anaemia
- transient erythroblastopenia of childhood
- parvovirus B19

• Diagnostic clue
- low reticulocyte count despite low Hb
- normal bilirubin
- negative direct antiglobulin test
(Coombs test)
- absent red cell precursors on bone marrow
examination.

Aplastic anaemia: Fanconi anemia
• Most common inherited type
• Autosomal recessive diorder due to genetic
defect DNA repair.
• Usually oocur among 5 to 10 years old
children.
• 10% developed acute myeloblastic anemia

- Growth retardation & congenital effect of
skeleton
- short stature, abnormal thumb and radii,
microcephaly, micropthalmia, café au lait &
hypopigmented spot, renal structural
abnormality

• Management
- bone marrow transplantation using normal
donor bone marrow from unaffected siblings
or matched unrelated marrow donor.

Increased red cell destruction
(haemolytic anemia)
• Causes
- red cell membrane disorders
*Hereditary spherocytosis
- red cell enzyme disorder
*G6PD deficiency
- haemoglobinopathies
*Sickle cell disease, B-thalassaemia major

red cell membrane disorders:
Hereditary spherocytosis
• Autosomal dominant inheritance but 25% of
cases there is no family history
• May cause early, severe jaundice in newborn
infants.
- usually asymptomatic
- jaundice, anemia, mild to moderate
splnomegaly, aplastic crisis & gallstones
• Management
- oral folic acid, splenectomy if symptomatic

red cell enzyme disorder:
G6PD deficiency
• Commonest red cell enzymopathy
• Is x-linked recessive (predominantly affect male)
• May present with neonatal jaundice
• Causes acute intermittent hemolysis precipatated by
infection, certain drugs, fava bean & naphthalene.
• Associated with jaundice, dark urine, fever, malaise
• Management
- parents should be given advice about the sign of acute
hemolysis and give a list of drugs, chemicals and food
to avoid.

Haemoglobinopathies:
Sickle cell disease
• Autosomal recessive
• SCD result in ischemia in organ
- anemia, infection, painful crises, squestration crises,
splenomegaly, growth failure, gallstone
- Serious complication are bacterial infection, acute chest
syndrome, stroke and priapism.
• Management
- Treatment of acute crisis- oral or IV analgesia and good
hydration
- Treatment of chronic problem- hydroxyurea to increase
HbF, bone marrow transplant

haemoglobinopathies:
B-thalassaemia major
• Mutation of B-globin gene result in an inability
to prodece HbA
- severe anemia, growth failure, pallor,
jaundice, bossing of skull, maxillary
overgrowth, splenomegaly, hepatomegaly,
need for repeated blood transfusion

• Management
- life long blood transfusion
• Complication of long rem-blood transfusion in
children
- iron deposition
- antibody formation
- infection

Anaemia in the newborn
• Reduced RBC production
• Increased RBC destruction
• Blood loss
• Anaemia of prematurity

Blood loss
• Main causes
- feto-maternal haemorrhage
- twin-to-twin transfussion
- blood loss around the time of delivery
• Main diagnostic clue
- severe anemia with a raised reticulocyte
count and normal bilirubin

Anaemia of prematurity
• Main causes
- inadequate erythropoietin production
- reduced red cell lifespan
- frequent blood sampling whilst in hospital
- iron and folic acid deficiency (after 2-3
months)

PHYSIOLOGICAL CHANGES IN
PREGNANCY

ESSENTIAL FOR:
Support and protection to developing fetus
To prepare the mother for labour and delivery
CHANGES ARE DUE TO:
Hormonal alteration
Increased metabolic
Mechanical factor of gravid uterus

WHY STUDY THE CHANGES???
To differentiate normal from abnormal
To make the process of delivery smooth
To anticipate and manage complications

HEMATOLOGICAL SYSTEM
1) Plasma volume
o Begin to ↑ to 10% at 7 weeks and increasing
rapidly, then plateauing at 40-50% by 32
weeks.
o At the same time,red cell volume also ↑ by
15-20% → help to improve utero-placental
perfusion

2) Red cell mass
Red cell mass expansion < blood volume expansion
Total net of blood conc./viscosity ↓ by 20%
(condition known as hemodilution)
Dilutional anemia
(physiological anemia)
Oedema in pregnancy
d/t drop colloid oncotic
pressure

3) Blood component
o ↑ total vol. RBC up to 25% d/t elevated level
erythropoeitin →provide extra O₂ demand
o WBC can go up to 15,000-16,000/mm3
o Platelet slightly fall d/t dilutional effect
o ↑ clotting factors(VII,VIII,IX,X) and
fibrinogen→protect from hemorrhage at
delivery

• Severe anemia may weaken the uterine
muscle strength which leads to uterine atony,
that leads to post partum hemorrhage
• Anemia can also lower resistance to infectious
disease
• However, the impact of anaemia on the extent
of blood lost at childbirth and postpartum is
not well-understood.
How ‘anemia’ cause increased risk of
PPH ?

• Check ferritin in early pregnancy: give iron
supplements only if iron deficient
• Folic acid 5mg daily is required.
• Parenteral iron should be avoided
• The aim during pregnancy is to maintain pre-
transfusion Hb concentration level above
10g/dL
How do you manage a patient with
thalassemia during pregnancy ?

• Thalassemia screening of the partner; If both
positive, the couple need counselling on the risk
of pregnancy with thalassemia major.
• Evaluation of cardiac function by ECHO, and of
liver and thyroid functions, in each trimester
(Main risk to the mother is cardiac
complications).
• Iron chelation therapy is complex and should be
tailored to the needs of the individual woman.
Others

Contents
 Definition of anaemia in pregnancy
 Prevalence of anaemia in pregnancy
 Causes of anaemia in pregnancy
 Iron-deficiency anaemia
- factors affecting Iron absorption
- types (Prepartum anaemia, IDA during Pregnancy,
Anemia + Post partum hemorrhage)
- signs & symptoms of IDA
- advice on how to take Iron tablet

Definition of anaemia in pregnancy
During Pregnancy
Haemoglobin
(g/dL)
WHO < 11
CDC < 11 (1ST trimester)
< 10.5 (2nd trimester)
< 11 (3rd trimester)
Post partum
Haemoglobin (g/dL) <10

Prevalence of anemia in pregnancy
World 47% 42% 30%
Malaysia 32% 38% 30%
Pre-school children Pregnant women
Non-pregnant women during
child bearing age
WHO Global Database on Anemia

Prevalence (contd.)
• Developing countries
– Africa 35% to 56%
– Asia 37% to 75%
– Latin America 37% to 52%
• Industralised countries- mean prevalence 18%
• HSNZ- 70.8%

 Insufficient intake/insufficient production : nutrition,
blood disease
 Increase loss : bleeding, renal disease, infestation of
parasites
 Increase demand : placenta, fetus, red blood cells
expansion
Causes of anaemia in pregnancy

Iron-deficiency Anaemia
(commonest cause)

The most frequent nutritional disorder
How many suffer from iron deficiency anemia?
2 billion peoples
1/3rd of the world’s population

Factors affecting Iron absorption
 Iron Absorption Enhancers
- Vitamin C; citrus fruit and juice, kiwi,
strawberries, tomatoes, etc
 Iron Absorption Inhibitors
- Iron binding polyphenol: red wine
- Coffee & tea
- Eggs
- Milk

Prepartum anemia
• Among fertile, non-
pregnant women, ∼40%
have ferritin of ≤30
μg/L(low iron status)
• Prepartum IDA
predisposes to
postpartum IDA- some
amt blood loss during
labour, lactation,
dilutional effect of
pregnancy
Test Level Remarks
Serum Ferritin (ug/L) < 30 Low iron status
< 15 Iron deficiency

Iron requirement in pregnancy
100mg/day iron for all
women*
9x higher
Iron
requirement
during
pregnancy

Anemia and Post Partum Hemorrhage
• Anaemia increase the risk of PPH
• Unability of uterus to contract
• Risk of DIVC higher
• Risk of post partum hysterectomy higher

Post-partum Anemia
“More than 80 percent of maternal
deaths are caused by haemorrhage,……
Most of these deaths are preventable
when there is access to adequate
reproductive health service”

Post partum anemia
• Severe postpartum anemia is a complication of 5% of
deliveries
• Following delivery, women lose some amount of iron
through breastfeeding and lactation
• IDA has been associated with impaired cognitive function
and behavioral disturbances in postpartum women
• Mother’s iron status should be evaluated prior
to discharge to monitor postpartum anemia

Post partum anemia
• Iron deficiency persists beyond the 4-6 weeks
postpartum period
– 12% of women are iron deficient up to 12 months
after delivery
– 8% of women are iron deficient 13-24 months after
delivery
• Iron supplementation should continue after
delivery if iron status remains low or while the
mother is breastfeeding

Sign & Symptoms of IDA
HEADACHES
COLD HANDS
& FEET
WEAKNESS,
FATIGUE,
SHORTNESS OF
BREATH
DIZZINESSPALE SKIN

PALLOR
KOilonychia
ANGULAR STOMATITIS
ATROPHIC GLOSSITIS
CHEALITIS
Clinical sign of anaemia

Management of Anemia in
pregnancy

Method Pros Cons
Oral Iron Cheap, Easy to take, Hardly
any serious side effects
Slow to act, Compliance
issue
Parenteral Iron Faster action, ensure
compliance
Cause anaphylactic
reaction, Pain and skin
discoloration at
injection.
Blood Transfusion Treat anemia almost
instantly
Mismatch, Blood
reaction, Disease
(Hepatitis, HIV), Fluid
Overload

• IDA is treated mainly with iron supplements
• Iron supplements have 2 forms, oral and
parenteral. Oral iron is most commonly used
• Use of iron supplements helps in improving
the iron status of the mother during
pregnancy and during the postpartum period,
even in women who enter pregnancy with
reasonable iron stores
Iron Supplements

• Oral Iron (200 – 300 mg of elemental iron) with
folic acid (500 microgram) prescribed in divided
dose
• Type of oral supplement available :
- Ferrous fumarate
- Ferrous gluconate (If the above is not tolerated)
- Ferrous glycine sulphate
- Ferrous sulphate (dry)
- Iron polysaccharide
• Why Ferrous fumarate ?
- Least expensive and best absorbed form of iron
- Newer drugs ? Not proven yet
Oral Iron Supplements

• Anorexia
• Diarrhea
• Epigastric Discomfort (Combination with Vit C
supplements)
• Nausea, Vomiting
• Constipation and Dark colored stool
• Temporary staining of teeth
*Oral Iron therapy must be continued for at least 12 months
after the anemia has been corrected in order to replenish the
depleted iron stores
Side Effects

• Start with one tablet daily first, then increase
gradually until three times daily dosing
• Avoid use of high-dose Vit C supplements
• Taking with meals (But can also reduced iron
absorption) – One hour before meal
• Administer at bed time
Methods of reducing side effects

• Daily oral iron and folic acid supplementation
is recommended as part of the antenatal care
to reduce the risk of low birth weight,
maternal anaemia and iron deficiency (strong
recommendation)
WHO Recommendation

• a 30 mg of elemental iron equals 150 mg of ferrous sulfate heptahydrate, 90
mg of ferrous fumarate or 250 mg of ferrous gluconate.
Suggested scheme
Supplement composition Iron: 30–60 mg of elemental
iron
Folic acid: 400 μg (0.4 mg)
Frequency One supplement daily
Duration Throughout pregnancy. Iron
and folic acid supplementation
should begin as early as
possible
Target group All pregnant adolescents and
adult women
Settings All settings

• An agent that increase the hemoglobin level
and the number of erythrocytes in the blood
• Drug to stimulate RBC formation
• Primarily used in treatment of anemia
• Example –
- Iron (Oral, Parenteral)
- Folic Acid
- Vit B12
What is ‘hematinic’

According to period of gestation :
Less than 30 Weeks – Oral iron with folic acid
30 – 36 weeks – Parenteral Iron Therapy
Greater than 36 weeks – Blood Transfusion
Management of IDA in pregnancy

Advice on how to take iron tablet:
take several times a day on an empty stomach.
best to be taken at;
-bedtime
-or about an hour before a meal and at the same time drink
juice that's rich in vitamin C, such as a glass of orange juice for
optimum absorption of iron.

• Increased in reticulocytes
- Increased 2 – 16%, by 4 – 6 days (earliest), pekas at 9 –
12 days.
• Increased in hemoglobin levels (Rising at rate of 2 g/dl
after 3 weeks)
• Total Plasma Iron will gradually increase and TIBC will
return to normal in about a month
• Blood ferritin levels return to normal in about 4 – 6
months
• Epithelial Changes (eg. Tongue and nails) revert to
normal
Increased in Hb in oral therapy

*Given over 6 – 8 hours under constant observation
Parenteral forms of Iron
Iron preparation Route Elemental Iron Content
Iron Dextran
(Imferon)
IM or IV 1ml = 50 mg Ferric
Hydroxide +
Dextran
Iron sorbitol
citrate complex
(Jectofer)
IV 1ml = 50mg Ferric Iron,
sorbitol and
citric acid
Iron sucrose IV 1ml = 2mg Iron-ferric
hydroxide in
sucrose

• Intolerance to oral form of iron
• When iron deficiency is not correctable with oral
treatment
• Non-compliance on part of the patient (Repeatly
fails to heed instructions/incapable of following
them)
• Patient suffering from Inflammatory Bowel
Disease (Aggravated by oral iron therapy)
• Patient is unable to absorb iron orally
• Patients near term (32 – 36 weeks of pregnancy)
Indication of use of parenteral iron
therapy

• IM - Pain and staining of the skin at the site of
injection + Development of fever, chills,
myalgia, athralgia, injection abscess
• IV - Serious side effect like anaphylaxis
reactions (0.7%)
• Both – Systemic reactions
Immediate : Hypotension, headache, malaise
Delayed : Lymphadenopathy, myalgia,
athralgia
Side Effects

• There is not enough time to achieve a
reasonable Hb level before delivery. (For
example, patient presents with severe anemia
beyond 36 weeks)
• There is acute blood loss or associated
infections
• Anemia is refractory to iron therapy
Indication for blood transfusion

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