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Iron Deficiency
 Incidence & Etiology
 Iron is one of the most common elements
in the earth's crust, yet Fe deficiency is
the most common cause of anemia
affecting about 500 million people world
wide.
Why?

 The body has a limited ability to absorb

Fe.
 Excess loss of Fe due to hemorrhage is
frequent.
 The body of the newborn infant contains about
0.5 gm of iron.

 Iron stores are built up in the last trimester of

pregnancy. Preterm and low birth wt. infants
are associated with decreased Fe stores.

 As the Hb conc. of the newborn infant fall

during the 1st 2-3 mo. of life, Fe stores are
reclaimed & are usually sufficient for blood
formation in the 1st 6-9 mo. of life in term
infants.
 Anemia caused by inadequate dietary Fe is
unusual below six months.

 It is mainly due to perinatal blood loss , in

preterm and low birth weight infants with
depleted iron stores.
BODY IRON DISTRIBUTION AND
TRANSPORT

 The transport and storage of iron is

largely mediated by 3 proteins:

1. Transferrin
2. Transferrin receptor (TR)
3. Ferritin
 Transferrin delivers Fe to tissues which
have tR especially erythroblast in bone
marrow which incorporate Fe into Hb
molecules .

 Most of Fe on transferrin is provided from

senescent RBC‘s and a small portion
comes from dietary Fe .

 Fe is stored in RE cells as ferritin on or

hemosiderin, in a ferric form .
 Iron is mobilized after reduction to ferrous form (vit.
C is involved)

 Iron is also present in muscle as myoglobin and Fe

containing enzymes as:

 catalase ,cytochrome ,mitochondrial

dehydrogenase.
 monoamine oxidase, peroxidase, xanthine oxidase.
 α-glycerol phosphate dehydrogenase.
 DIETARY REQUIREMENTS

 1 mg /kg to a max. of 15 mg /day

 2 mg /kg to a max. of 15 mg /day

for the preterm and LBW infants and
those who have significant perinatal
blood loss
 Iron deficiency is the most prevalent
single deficiency state worldwide.

 Stores are reduced before deficiency is

diagnosed.

Iron deficiency is not an enough

diagnosis

A cause needs to be identified!

 CAUSES OF IRON DEFICIENCY

 Decreased intake .

 Blood loss.

 Decreased absorption .
 Stages of Iron Deficiency
 Iron deficiency is most commonly described as
occurring in three stages:

 1ST stage: iron depletion: a decrease in iron stores

without any effect on essential body iron.

 2ND stage: iron deficient erythropoiesis:

inadequacy of iron available to bone marrow &
tissues for normal biochemistry and function.

 3RD last, most severe stage is iron deficiency

anemia identified by a significant reduction in Hb
levels and a decrease in MCV.
 Stages of Iron Deficiency and their
Detectable Laboratory Abnormalities
Stage 1 Depleted -Low ferritin
-Absent bone
iron stores marrow iron

Stage 2 Latent iron In addition:

-High TIBC
deficiency -Low serum iron
-Raised serum
transf receptors
-Normal Hb
Stage 3 Iron In addition:
-Low hemoglobin
deficiency
Anemia -Low MCV
 Diagnosis
Besides the potential gold standard test of
response to iron therapy, and the invasive BM
examination, traditional diagnostic tests include:

 Peripheral smear, hemoglobin, MCV, and RDW.

 Serum iron, TIBC, transferrin saturation & serum
ferritin.
 Free erythrocyte zinc protoporphyrin.
 GIT assessment & occult blood in stools.

Additionally, there are two newer tests for iron

deficiency: soluble transferrin receptor assay
and reticulocyte hemoglobin content.
Hypochromic Microcytic Anemia, Anisocytosis (variation
in size) & Poikilocytosis (variation in shape).
Common Lab tests and cut-off values for
the diagnosis of Fe deficiency in children
Test age (years) Cut-off value
Serum iron   1-5 <30 ug/dl
TIBC 1-3 > 470 ug/dl
3-5 > 460 ug/dl
Tranferrin 1-3 < 8%
Saturation 3-5 < 9%
FE Zinc 1-5 > or equal to 90
Protoporphyrin ug/dl RBC
Serum ferritin 1-5 < 8-12 ug/l
Hb 1-5 < 11.0 g/dl
Common Lab tests and cut-off values for
the diagnosis of Fe deficiency in children
Test age (years) Cut-off value
Hematocrit 1-3 < 33%
3-5 < 34%
MCV 1-3 < 73 fl
3-5 < 76 fl
S transf recep. 1-5 >9 mg/l
MCHC 1-5 < 32 g/dl
Reticulocyte Hb 1-5 < 27 pico-gm/cell
content
RDW 1-5 >14.5%
 Limitations of Serum Iron
Interpretation
1. Can not detect the pre-anemic states of
functional iron deficiency.
2. Diurnal variations: Morning levels are generally
higher than afternoon or evening levels.
3. Increased with concomitant acute or chronic
inflammation, infection, malignancy, or liver
disease.
4. Varies greatly with lab errors e.g. syringe or
glass contamination with iron.
5. Increased with small doses of iron fortified
vitamins, or even a single injection of iron
dextran.
 Serum ferritin
 Good positive but not good negative.
 If low, it is a reliable, sensitive, non-invasive
parameter for early detection of Fe depletion.
 In children, the cut-off value is <12 ug/l.
 Limtations:
1. Being an acute phase reactant, its serum levels
increase in chronic inflammation, infection,
malignancy, collagenic diseases & liver diseases.
2. Wide variations for age, sex.
3. level varies with lab method ( ELISA, RIA, or
immunoradiometric assay {IRMA})
For these reasons, serum level doesn’t well
correlate with the severity of iron deficiency
 Diagnosis (cont.)
 Increased (TIBC)> 460 ug/dl is a highly
sensitive and selective for Fe deficiency.
 Transferrin saturation < 9 % is diagnostic of
iron deficiency.
 MCV< 76 fl, hypochromic microcytic anemia with
marked degree of anisopoikilocytosis, and wide
RDW are highly indicative of Fe deficiency.
 Limitation to MCV!
• Combined folate deficiency and Fe deficiency can
occur (e.g. PEM), revealing a population of
macrocytes mixed with the hypo-microcytic cells.
• This combination can normalize the MCV. This is
known as Dimorphic blood picture.
Corrected Reticulocyte count
 Helps to differentiate between iron def &
thalassemia.
 Can be used as a response parameter to
iron therapy.
 To be useful, the reticulocyte count must
be adjusted for the patient's hematocrit
by the following formula:
Corrected retic. count = Patient retic. x
(measured Hct/ Normal Hct)i.e.(pt Hct/45)

 The normal corrected retic is 1 - 2%.

Red cell distribution width (RDW)
 It is an index of the variation in the size of RBCs
& can detect subtle degrees of anisocytosis.
 Elevated RDW appears to be one of the earliest
haematological manifestation of iron deficiency.
 Significance:
• HIGH: Fe deficiency.
• NORMAL: Anemia of chronic disease.
• SLIGHT INCREASE: Thalassemia.
 Calculated by the following formula:
RDW= SD of MCV x 100/MCV
NEW PARAMETERS
 Serum soluble transferrin
receptor assay (sTfR)
 It detects iron availability at the cellular level &
increased in iron deficiency.

 High values are present in pre-anemic patients with Fe

deficient erythropoiesis or Fe deficiency anemia.
Normal range is 3-9 mg/l.

 Provides a more stable measurement than transferrin

saturation & affected earlier than traditional
parameters such as MCV or Zn-FEP.
 Unlike serum ferritin, (sTfR) remains normal in
patients with acute or chronic inflammation or liver
disease.
 Serum soluble transferrin
receptor assay (sTfR)
 Effective in distinguishing iron deficiency
anemia from anemia of chronic disease.

 Limitations:

1. High cost.
2. Variability with the used lab method.
 Reticulocyte Hemoglobin
Content (CHr)
 (CHr) is an early measure of functional iron
deficiency because the only cells being measured
are those recently released from the B.M.
 Very sensitive in detecting recent iron deficiency.
 Can be used to assess therapeutic response to
iron more quickly than hematocrit measures.
 (CHr) is a useful, sensitive, early screening test
in infants and young children.
 It was determined that (CHr) < 27 picogm/cell
is the optimal cut-off value to diagnose iron
deficiency.
 Differential diagnosis of iron
deficiency anemia
 First of all, we should investigate for a possible
GIT cause. (Chronic blood loss, malabsorption,
or concomitant H-pylori infection, a recently
identified aggravating factor for Fe deficiency).
 D.D. includes:
1. ß- Thalassemia trait.
2. Anemia of chronic disease.
3. Lead poisoning.
4. Sideroblastic Anemia.
5. pyridoxine deficiency.
CAUSES OF HYPOCHROMIC MICROCYTIC ANEMIA

IRON PROTOPORPHYRIN

Fe DEFICIENCY
SIDEROBLASTIC
.CHRONIC INF
ANEMIA
MALIGNANCY

+
HAEM GLOBIN

THALASSEMIA
HAEMOGLOBIN
 Differentiation between Iron
deficiency & Thalassemia trait
 A calculation using red cell indices helps to
identify the possible cause of microcytosis:
RDW-to-RBC ratio = (RDW) / (RBC in millions)
Interpretation:
• Iron deficiency: > 3.3
• Thalassemia minor: < 3.3

 In thalassemia, the MCV is uniformly very low

(below 50), in contrast to Fe deficiency where
MCV is usually higher with a more degree of
anisocytosis.
CBC of beta thalassemia trait, low MCV, with less degree of anisocytosis
 Iron Deficiency – Lead toxicity
 Fe def Can lead to Lead poisoning secondary to
pica:
• Iron deficiency enhances uptake of heavy metals.
• Lead is still used in all outside house paint & is highly
concentrated in the first few inches of soil (car exhaust)
 Diagnosis of lead poisoning:
 Basophilic stippling of RBCs
 Mild microcytosis.
 Markedly high serum free erythrocyte Zn
protoporphyrin.
 Definite diagnosis by measuring serum lead level.
Screening is recommended at the age of 1year.
 Basophilic stippling, hypochromic microcytic
anemia,anisopoikilocytosis (suggestive of lead poisoning)
 Treatment
 Oral ferrous preparations (Fe sulphate,
gluconate, or fumarate) (6 mg/kg/ day)
Oral iron failure ?!
 Incorrect diagnosis (eg, thalassemia trait, or anemia

of chronic disease)
 Poor compliance.

 Ongoing blood loss (Ankylostoma, hiatal hernia,

Meckel's div., Piles, Cow milk allergy etc.)

 Malabsorption: inflammatory bowel disease, Celiac…

 Concomitant nutritional deficiency (e.g.Folic acid)

 Concomitant H-pylori infection.

 Concluding Remarks
 Errors in the diagnosis and treatment of
iron-deficiency anemia involve several
areas in history, physical examination &
laboratory investigations.
 Anemia is a sign, not a disease.
 Anemia is a dynamic process including
different stages.
 Most importantly, the diagnosis of iron
deficiency anemia mandates further work-
up to detect the cause.
THANK YOU...