Iron deficiency

anaemia

DR OKITE
Outline
 Introduction
 Etiology
 ClinicalFeatures
 Laboratory Features
 Treatment
 Differential Diagnosis
 Conclusions
 References
Intro….
 Iron is a transition metal with mol.
weight of 55.85KD.
 It’s ability to exist in more than one
oxidative state and form complexes
underlies is various metabolic functions.
Intro…
 Iron is very important in maintaining
many body functions including ;
 the synthesis of haemoglobin and
oxygen transport.
 normal growth, maintenance and
survival of tissues.
 motor and cognitive development.
Intro…
 Despite it’s abundant supply in nature,
deficiency is common.
 Iron metabolism is a tightly regulated
process as the body lacks the
mechanism of excreting it.
Intro…
 Iron deficiency is a result of the imbalance
of iron uptake, absorption and iron loss.

 It develops when body stores of iron drop

too low to support Erythropoiesis.

 Begins with stage of iron depletion, iron

deficient erythropoiesis and Iron
deficiency Anaemia(IDA).
Intro…
 Iron deficiency is the most common
cause of anaemia throughout the world
 The most common cause of microcytic
hypochromic anaemia.
 Commonly occur in children and women
due to insufficient dietary intake and
menstruation respectively.
 Chronic bleeding underlies IDA in men
and postmenopausal women respectively.
Brief history…
 It was known as “Chlorosis” or green
sickness by mid 16th century European
physicians.
 In mid 17th century, iron salt was used for
treatment.
 Sydenham recommended Iron therapy as
the specific treatment option
 It wasn’t until the 20th century( 1923) that
Heath, Strauss, and Castle did a classic
study on IDA.
Epidemiology
 A major public health problem affecting
30% of world population.
 40% of global burden of ID is reported to
occur in SE Asia.
 Incidence rates range from 7.2 to 13.96 per
1000 person years
 IDA due to poor dietary intake is commoner
in developing countries while blood loss
account for those in developed countries .
Epidemiology…
 In a study conducted by Olufemi, J.A etal
at LASUTH in 2010 revealed the
prevalence IDA as 69% among
preschool children.
 52% prevalence among Non pregnant
women of reproductive age.
 There is no race predilection, however
blacks tend to be more affected due to
poor dietary intake.
Risk factor
 Menstruating women
 Pregnant women
 Trauma and major surgeries like gastric
bypass operations
 PUD patients
 Children who drink Cow milk
Decreased intake Impaired Increased Increased
absorption loss demand

Diets low in iron Achlorhydria Chronic pregnancy

Gastrectomy blood loss
/gastric from any
bypass site: GIT,
Etiology surgery heamaturia,
epistaxis

Low quantity of Celiac Gynaecologi lactation

bioavailable iron disease cal loss,
H. Pylori Bleeding
infection disoders

Less food intake Phytates, NSAIDS, Infancy ,

tannins Asprin Adolescents
Frequent
donation
NSAIDS, Parasitic Menstruatio
Asprin, H2 infestation- n
BLOCKERS, hookworm
PPIs
Stages of IDA
Contd…
 Depletion of iron stores
 When the body is in a state of negative
iron balance, the first event is depletion
of body stores, which are mobilized for
haemoglobin production.
 Increased iron absorption
 Reduced serum ferritin
Iron Def.erythropoiesis
 With further iron depletion, when the serum
ferritin is below 15 μg/L, the serum
transferrin saturation falls to less than 15%
due to a rise in transferrin concentration and
a fall in serum iron. (ferritin males= 15-300;
ferritin females 15-150)
 iron-deficient erythropoiesis and increasing
concentrations of serum transferrin receptor
and red cell protoporphyrin
 Reduced sideroblast
Iron Def. Anaemia
 If the negative balance continues, frank iron deficiency
anaemia develops.
 The red cells become obviously microcytic and
hypochromic and poikilocytosis becomes more
marked.
 The MCV and MCH are reduced, and target cells may be
present.
 The reticulocyte count is low for the degree of anaemia.
 The serum TIBC rises and the serum iron falls, so that
the percentage saturation of the TIBC is usually less
than 10%.
 Absent siderotic granules
Contd…
Clinical features
 Symptoms of Anaemia;
 Easy fatique, weakness, dizziness,
dyspnoea, tachycardia with palpitations
 Headache and even angina pectoris.
 Symptoms of underlying pathology
Non haematological
manifestation
 Decreasedwork performance as
measured by peak oxygen
consumption(VO2).
 poor attention span, poor response to
sensory stimuli, and retarded behavioral
and developmental achievement even
in the absence of anaemia.
 Impaired immunity- cell mediated
immunity.
Contd…
 Headaches, and paraesthesia are said to
be neurological complications of IDA
 Nail changes – brittle, lusterless and
flat; in advanced cases, their shape
changes from normal convex to concave
(koilonychia)
 Unusual cravings e.g for ice, clay(pica),
dirt, laundry starch, salt, cardboard,
and hair.
Clinical features
 Plummer-Vinson ( or Patterson-Kelly)
syndrome. mucosal atrophy may lead to
web formation in the post cricoid region,
thereby giving rise to dysphagia and
glossitis.
 Longer duration may lead to pharyngeal
carcinoma
Contd…
 Glossitis (smooth, red tongue),
stomatitis, and angular cheilitis.
 Impaired growth- dividing cells need
iron
 Splenomegaly in severe persistent cases
is usually due to an underlying cause.
Lab investigations
 FBC
 PBF
 BMA
 Ironstudies
 Investigations for underlying cause
Parameter Reference Change in IDA
range
Hb (g/dl) F-13.5, M-15.0 F<12,M<13,PW<
11
MCV (Fl) MCV 80-100 MCV <80
MCH (pg) MCH 29.5 MCH<27
MCHC(g/dl) 33.0 Reduced in
severe disease
RDW(%) 12.8 Increased >14
CHr (pg) Reduced <29
%Hypochromic <5 Increased
cells
Serum iron(ug/dl) 60-180 Reduced
TIBC(ug/dl) 250-450 Elevated
%TS <16
SF (ug/L) 20-200 Reduced <16
sTfR Lab to establish Elevated
ZPP/FEP <40 Elevated
(umol/mol heme)
BM iron 1+ to 3+ Absent
Contd…
 FBC- Reduction in Hb and Hct defines the last
stage of ID.
 Red cell indices-Red cell mass, MCV, MCH,
are reduced. MCHC-reduced in severe
disease. Reduction is proportional to the
severity and duration of anaemia.
 Thrombocytosis. Normal WBC.
 RDW(CV/SD)- a measure of anisocytosis of
red cell. is elevated early in IDA. Normal in B-
Thalassemia.
Contd…
 PBF- Hypochromic, microcytic cells,
pencil shaped poikilocytes.
 Wbc has normal morphology
 Platelet may be raised.
Contd…
 BMA- examined for Haemosiderin, is
specific for ID and is the gold
standard for evaluation of iron stores.
 erythropoiesis is micronormoblastic. The
micronormoblasts are smaller than
normal with reduced amount of
cytoplasm that is vacuolated and has
ragged cell borders.
.
 Prussian blue helps identify iron
granules in erythroid precursors and
macrophages.
 Positivity is graded on the basis of
intensity of staining from 1 to 6.
 Normoblast showing siderotic blue
granules are called sideroblast
Biochemical test( iron
studies)
 Serum iron- asses iron stores, reduced
in IDA.
 It shows diurnal variation with higher
conc. Seen later in the day. Testing is
best done in a fasting state
 Low in Anaemia of chronic disease.
 TIBC- elevated values is specific for ID
but has a low sensitivity.
Contd…
 %Transferrin saturation- shows diurnal
variation, has acute phase reactivity.
 These markers are altered by inflammation.
 Serum Ferritin- correlates with Total body iron
stores. Non invasive, widely available, specific
and frequently used to diagnose ID. Low SF is a
reliable index, but rises in inflammation/infection
and malignancy, Therefore, %TS is employed to
diagnose ID.
 Measurement of other markers of inflammation
like CRP will be low.
Contd…
 Zinc protoporphyrin/Free Erythrocyte
protoporphyrin;
 Protoporphyrin is normally produced during synthesis
of Hb.
 FEP is elevated in IDA as less iron is available for Hb
synthesis.
 Detects stage II ID, measured in a
hematofluorometer. Used as screening test in field
survey.
 Elevated in infection, lead poisoning, hemolysis.
 Diagnostic of IDA following PBF- microcytic
hypochromic anaemia.
Contd…
 Serum TfR- reflects the functional iron
compartment
 increased in IDA and Haemolytic anaemia.
 Measured using ELISA assays.
 More specific to changes in iron status and
erythropoiesis
 Detect tissue ID before Anaemia sets in.
 Lack of standardised reference material
cutoffs limits it’s use.
contd…
 sTfR/LogFerritin index- this ratio provides
a better indicator of iron depletion than
either of the tests alone.
 Both variables are influenced by iron stores,
availability of iron for erythropoiesis and
total erythroid marrow mass.
 Highly sensitive and specific
 High index in IDA(2-3), low in anaemia of
chronic disease.
Contd…
 Serum Hepcidin-
 ELISA assay using anti hepcidin antibodies and mass
spectrometry.
 Shows diurnal variation with lower levels seen in the
morning.
 Identify those who will benefit from oral iron therapy.
(good response with low values), ( no response with
normal or elevated values)
 Lower in women
 Urinary hepcidin estimation requires measurement of
creatinine to correct for the difference in the
concentrating ability of the kidney.
To determine underlying
cause of IDA

 Thismay be obvious (e.g. bleeding) or

may require tests such as GIT work-up
esp. in adults (test for faecal occult
blood, endoscopy or radiology), pelvic
ultrasound in females (if menorrhagia is
present), stool examination for
hookworm, etc.
Treatment
 Treatment is with iron supplementation
given orally or by parenteral route.
 Aim of treatment is to correct the Hb
concentration and also replenish iron
stores.
 Diet, medication & transfusion
 oral therapy:
 Convenient, cheap, effective,easy to obtain
and first choice of treatment in most cases.
Oral formulation
 The most commonly used ones are;
ferrous sulphate, fumarate, and
gluconate.
 Indicated when Hb conc. Is <12g/dl and
>8g/dl.
 Recommended daily dose for adults with
ID is 100-200mg of elemental iron while
children is 3-6mg/kg of liquid prep.
Contd…
 Preferable to take iron without food, but
side effects; nausea and vomiting,
epigastric discomfort, constipation,
diarrhea, metallic taste, and dark stool.
 Meals reduces absorption.
 Sustained release are better tolerated
but expensive, absorption is reduced.
Contd…
 Duration of therapy:
 Given till Hb conc. reaches normal
values, then continued for 3-6months to
replenish stores.
 Failure of oral therapy:
 Lack of adherence
 Low tolerance, incorrect diagnosis
 True refractoriness.
Parenteral formulation
 Indicated; when oral therapy is poorly
tolerated
 Poor or not responding to therapy
 Malabsorption
 Chronic blood loss, with poor control of
bleeding.
 Common preps; ferric carboxymaltose,
iron dextran, iron sucrose.
 This compound has a core of iron salt
surrounded by carbohydrate shell.
 IV Iron can be given as single or multiple
dose
 Single dose prep( iron dextran,
ferumoxytol, ferric carboxymaltose, iron
isomaltoside .
 High doses of 500- 1000mg can be
given.
Contd…
 Multiple dose- iron sucrose, ferrous
gluconate.
 For better delivery and replacement
 Replenishes iron stores more effectively
and increases Hb more quickly.
 Ferumoxyltol
 Iron nanoparticles(iron hydroxide adipate
tartrate) mimics ferritin molecule which
have high bioavailability are under trial
Indication for parenteral iron
 Hb</=8g/dl
 Intolerance/not responsive to oral iron
 Rapid correction of anaemia is needed
 Iron malabsorption
 Ongoing blood loss
 Use with EPO in CKD
 Inflammatory bowel disease
 Substitute for blood transfusion( religious
reasons)
Contd…
 New preparations have extreme low risk
of serious side effect
 Do not require a test dose
 Given over a short period of time.
 Side effect- nausea and vomiting,
abdominal pain, headache, flushing,
myalgia, arthralgia, diarrhoea,
anaphylactic reactions have been
reported.
Monitoring
 Retic count- begins to rise 3-4days,
peaks at 5-7days and then return to
normal.
 Hb concentration- increases by second
week and normalises by 2 months of
initiation of therapy. An increase of 2g/dl
is appropriate .
 Other indices remains abnormal for
some time.
Follow up
 After normalization of Hb(4-6 weeks),
FBC and parameters of iron status must
be measured each month for 3 months
and then once every 3 months for a year.
 Ferritin should be checked every 3 to 4
months, if below 50ug/L, administer
another dose of IV iron
 Long term follow up may be necessary
for severe IDA
Caution
 Inmalaria endemic region, iron
supplementation may increase
parasitemia, worsen infections like
Acute respiratory illness, diarrhoea.
 Estimation of serum Hepcidin helps
determine best time for
supplementation.
Prevention
 Targeted at population at risk of IDA such
as pregnant women, infants, and children.
 Access to iron rich foods; meat, liver,
legumes, green leafy vegetable, kidney
beans and lentils
 Food fortification with iron supplements,
rice, bread, wheat flour, salt.
 Iron bio fortification of wheat, rice,
millets, beans, peas.
Contd…
 Children need additional iron after 6
months of breast feeding, give them
multiple micronutrient powders.
 WHO recommends micronutrients
powders which contain lipid
encapsulated iron with other
micronutrients in form of sachets for
children 6-23 month
 Deworming at regular interval
Contd…
 Delayed Cord clampimg : 1-3min after
delivery improves infant iron stores at 6
months of age. WHO recommendation.
 Regular screening for IDA for population
at risk.
Differential diagnosis
Differential diagnosis
Conclusion
 Iron deficiency anaemia is a major
public health issue especially in
developing climes like ours.
 Children, Adolescent and pregnant
women have the highest risk as a result
of increased demand.
 Early diagnosis and treatment offers
good outcome.
Thank you for listening