from the dacie todd and wintrobe . i prepared this . there is lot of things in iron metabolism . but all can not be included

1. Iron deficiency anemia-
pathophysiology and lab diagnosis
Dr. Bahoran Singh

2. Introduction
• Anemia is functionally defined as an insufficient RBC
mass to adequately deliver oxygen to peripheral
tissues.
• Anemia is considered to be present if the hemoglobin
(Hb) concentration or the hematocrit (Hct) is below the
lower limit of the 95% reference interval for the
individual’s age,sex, and geographic location .
• Anemia may be absolute, when red blood cell mass is
decreased, or relative, when associated with a higher
plasma volume.
• Causes of absolute anemia
• 1.impaired red cell production
• 2. increased erythrocyte destruction or loss in excess of
the ability of the marrow to replace these losses.

3. • Iron deficiency is the most common anaemia.
• 83-90% of all anemia constitute IDA
• Every day about 30 mg iron is used to make
new hemoglobin.
• Daily iron loss is around 1 mg.
• In women menstruation and childbirth
increase iron losses to about 1.5 mg/day.

4. • The total content of iron in the body - about 4.2g.
From them:
- 75-80% belongs to the hemoglobin
- 20 - 25% reserve
- 5-10% part of the myoglobin
-1% is part of the enzyme for the tissue respiration

5. DIETARY IRON
• There are 2 types of iron in the diet; heme
iron and non-heme iron.
• Heme iron is present in Hb containing animal
food like meat, liver & spleen.
• Non-heme iron is obtained from cereals,
vegetables & beans.

6. Ironcycle

7. • Most body iron is present in hemoglobin in
circulating red cells
• The macrophages of the reticuloendotelial
system store iron released from hemoglobin
as ferritin and hemosiderin.
• In the plasma, total iron averages 110 µg/dL
• Majority bound to the transferrin (capacity
to bind 330 µg of iron per deciliter)
• So only one third of transferrin is saturated.

8. IRON METABOLISM
• Iron concentration (Fe)
• N: 50-150 g/dl
• Total Iron Binding Capacity
• N: 250-450 g/dl
• Transferrin saturation
• Transferrin receptor concentration
• Ferritin concentration
• N: 50-300 g/l

9. Overview of Iron Homeostasis
erythr
oblast

10. IRON ABSORPTION
• Site- Proximal small intestine i.e. duodenum (first
part- maximum absorption) and jejunum.
• 10% of dietary iron is absorbed
• it is determined by intraluminal factor i.e. pH and
redox potential.
• Therapeutic ferrous iron is well absorbed on
empty stomach.
• Haem iron is not affected by ingestion of other
food items.
• Heme iron → Acid and gastric juices release it
from apoprotein → Oxidised → hemin → directly
absorb through mucosal cell intact.

11. INHIBITORS OF IRON ABSORPTION
• Food with polyphenol compounds
– Cereals like sorghum & oats
– Vegetables such as spinach and spices
– Beverages like tea, coffee, cocoa and wine.
– A single cup of tea taken with meal reduces iron
absorption by up to 11%.
• Food containing phytic acid i.e. Bran
• Cow’s milk due to its high calcium & casein
contents.

12. Promoters of Iron Absorption
• Foods containing ascorbic acid like citrus
fruits, broccoli & other dark green vegetables
• Foods containing muscle protein
• Food fermentation aids iron absorption by
reducing the phytate content of diet

13. Iron absorption at molecular level
• Iron is converted from Fe3+ to
Fe2+ by ferrireductase
(DCYTB).
• Fe2+ transported across
mucosal surface of enterocyte
by DMT1, stored as ferritin.
• Ferritin releases Fe2+ which is
transported across basolateral
surface of enterocyte with
help of ferroportin .
• Fe2+ converted back to Fe3+ by
Hephaestin .
• Fe3+ binds to transferrin in
plasma.

14. Regulation of Iron Absorption
• Regulated at two stages
– Mucosal uptake
– At stage of transfer to blood
• 1. HIF-2 ά- a mediator of cellular adaptation to
hypoxia, regulates DMT1 transcription and thus
regulates mucosal uptake of iron because
mucosal uptake depend on DMT 1.
• 2. Iron transfer to the plasma depends on the
requirements of the erythron for iron and the
level of iron stores.
• This regulation is mediated directly by hepcidin.

15. Cellular iron uptake & release

16. • The reticuloendothelial macrophages play a
major role in recycling iron resulting from the
degradation of haemoglobin from senescent
erythrocytes.
• They engulf red blood cells and release the
iron within using haem oxygenase.
• The protein transporting iron to plasma is
ferroportin.

17. Ferroportin and Hepcidin
• Hepcidin- its synthesis is controlled at molecular level.
• Interaction of diferric transferrin,bone morphogenetic
proteins (BMPs), interleukin (IL)-6 and other
inflammatory cytokines with cell surface receptors TfR1,
TfR2, hemojuvelin (HJV) and IL-6 receptor lead to
upregulation of the hepcidin gene.
• Mechanism of action- it binds to both TfR1 and TfR2,
decreasing the affinity of each for transferrin.
– Stabilization and endocytosis of TfR2 stimulates hepcidin
production
– Diferric transferrin displaces the protein HFE from TfR1,
leaving it free to interact with TfR2, thus stimulating
hepcidin production in response to plasma iron levels.

18. • Increased erythropoiesis causes decreased hepcidin.
Hepcidine function
– Blocks ferroportin
– Prevents absorption of iron from enterocytes.
– Prevents iron exportation from macrophages.
– Increased in inflammation.
– Leads to reduced serum iron, microcytic anemia, and
incomplete response to iron therapy.
• Ferroportin
– Transporter protein of iron in enterocytes and macrophages.
– Blocked by hepcidin .

19. Newborn Iron Stores
• Endowed with 75 mg/kg of iron at birth
• Dependent on hemoglobin concentration at
birth (majority of iron in circulating RBCs)
• Depleted by 3 months in low birth weight
infants without supplementation
• Depleted by age 5-6 months in term infants
• Delayed cord clamping (by 2 minutes) leads to
higher ferritin and iron stores at 6 months of
age

20. Iron storage
• Iron stored in two forms
– Soluble ferritin
– Insoluble hemosiderin- denatured form of ferritin
in which the protein shells have partly degraded,
allowing the iron cores to aggregate.
• Hemosiderin deposits are seen on Prussian-blue
positivity after staining of tissue sections with
potassium ferrocyanide in acid.

21. Regulation of Iron Metabolism
• Iron metabolism is regulated post transcriptionally by iron
regulatory proteins- IRP 1 and IRP 2.
• The conformation of IRP1 required for binding to mRNA
iron-responsive elements (IREs).
• IRP2 are directly affected by the amount of iron within a
cell.
• When the labile iron pool is deficient of iron, IRP1 has
an available binding site for IRE.
• When the labile iron pool is saturated with iron, the iron
binds to IRP1 to produce a 4Fe-4S cluster which blocks the
IRE binding site and prevents IRP1 binding to the IRE.
• In the presence of iron, IRP2 is degraded.
• Regulation of iron proteins by IRP on basis of location of IRE
on mRNA
– at 3’UTR- Stabiles translocation of TfR & DMT 1
– 5’UTR- inhibit translation of mRNA

22. IRON TRANSPORT
• Transferrin is the major protein responsible for
transporting iron in the body
• Transferrin receptors, located in almost all cells of
the body, can bind two molecules of transferrin.
• One molecule of transferrin binds two molecules
of iron.
• Both transferrin saturation & transferrin
receptors are important in assessing iron status

23. • Transferrin, when incompletely saturated with
iron, exists in four forms:
1. Apotranferrin
2. Monoferrric transferrin A
3. Monoferrric transferrin B
4. Diferric Transferrin
• There distribution may be determined by urea-
polyacrylamide electrophoresis.
• The plasma iron pool (transferrin-bound iron)
is about 3 mg.

24. Other iron transporter proteins
1. Haptoglobin- Serum glycoprotein
• It binds with Hemoglobin άẞ dimer released into
the bloodstream by hemolysis.
• Hemoglobin–haptoglobin complex is removed
from plasma by macrophages having receptor CD
163.
2. Hemopexin- Plasma glycoprotein that binds heme
and transports the haem to cells by a process that
involves receptor-mediated endocytosis

25. 3. Ferritin-
– present in low conc in plasma.
– Mostly appears as glycosylated and has low content of iron.
– It is also released into the circulation as a result of tissue
damage.
4. Non-transferrin-bound iron-
– Iron that is not bound to transferrin.
– Have low molecular mass and can be bound by specific iron
chelators.
– Chemical form is not known but rapidly removed from
circulation by liver.
– This removal involve zinc transporter ZIP14.

26. AT RISK GROUPS
1. Infants
2. Under 5 children
3. Children of school age
4. Women of child bearing age
5. Geriatric age group

27. Causes of iron deficiency
• Chronic blood loss
• Increased demand
• Malabsorbtion of iron
• Inadequate iron intake
• Intravascular hemolysis and hemoglobinuria-
hemosiderinuria
• Combinations

28. Increased demands
• Pregnancy
• Lactation
• Growing infants and children
• Menstruating women
• Multiparity
• Parturition

29. Decreased intake
• Decreased iron in the diet
– Vegetarian diet
– Low socioeconomic status
– Lack of balanced diet or poor intake
– Alcoholism
• Decreased absorbtion
– Gastric surgery
– Achlorhydria
– Duodenal pathology
– Chronic renal failure patients
– Coeliac Sprue
– Pica

30. Increased iron loss
• Menorrhagia
• Gastrointestinal
hemorrhage
• P.Ulcer
• Oesophagitis
• Varices
• Hiatal hernia
• Malignancy
• Angiodysplasia
• Diverticulosis
• Meckel
diverticula
• Colitis or
imperforated
bowel disease
• Hemorrhoids
• NSAID use
• Parasites

31. Increased iron loss
• Bleeding disorder
• Pulmonary lesions with bleeding
• Hemoglobinuria – hemosiderinuria (chronic
intravascular hemolysis)
• Hemodialysis
• Hematuria (chronic)
• Frequent donation
– 250 mg iron /unit-blood

32. Pathogenesis of iron deficiency anemia
• There are three pathogenic factors
– Impaired Hb synthesis d/t reduced iron supply
– Generalized defect in cellular proliferation
– Survival of erythroid precursor and erythrocytes is
reduced
When transferrin saturation ‹15%, marrow supply of
iron reduced and is inadequate to meet basal
requirement for Hb production.
– erythrocyte protoporphyrin raised
– each RBC contain less Hb so microcytic and
hypochromic

33. Clinical features of iron deficiency
anemia
• Fatigue and Other Nonspecific Symptoms
– irritability, palpitations, dizziness, breathlessness,
headache, and fatigue
• Neuromuscular System
– impair muscular performance, abnormalities in
muscle metabolism , behavioral disturbances,
– Neurologic development in infants and scholastic
performance in older children may be impaired.
– Sometimes neuralgia pains, vasomotor disturbances,
or numbness and tingling.

35. Epithelial tissues
Site findings
Nails Flattening
Koilonychia
Tongue Soreness
Mild papillary atrophy
Absence of filiform papillae
Mouth Angular stomatitis
Hypopharynx Dysphagia
Esophageal webs
Stomach Achlorhydria
Gastritis

36. Plummer-Vinson syndrome
• The most common
anatomic lesion is a
“web” of mucosa at the
juncture between the
hypopharynx and the
esophagus

37. • Immunity and Infection
– Defective lymphocyte-mediated immunity and impaired
bacterial killing by phagocytes.
• Pica
– “craving to eat earth”
• Pagophagia is, defined as the purposeful eating of at
least one tray of ice daily for 2 months,
• Food pica- compulsively eating one food, often
something that is brittle and makes a crunching sound
when chewed.
• Genitourinary System- Disturbances in menstruation,
• Skeletal System
– diploic spaces may be widened, and the outer tables
thinned

38. Developmental Stages of Iron
Deficiency Anemia (WHO)
• Pre-latent –
– reduction in iron stores without reduced serum iron levels
– Hb, MCV, Transferrin saturation- Normal, Iron absorption -
increase, Serum ferritin and marrow iron reduced
– no clinical manifestation
• Latent-
– iron stores are exhausted, but the blood hemoglobin level
remains normal
– index of the blood within the standard
– clinical picture is caused by the sideropenic syndrome
• Iron Deficiency Anemia
– blood hemoglobin concentration falls below the lower limit of
normal
– the clinical manifestations in the form of sideropenic syndrome
and general anemic symptoms

39. Stages in the Development of Iron
Deficiency
Stage 1 (Prelatent) Stage 2 (Latent) Stage 3 (Anemia)
Bone marrow iron Reduced Absent Absent
Serum ferritin Reduced <12 μg/L <12 μg/L
Transferrin saturation Normal <16% <16%
Free erythrocyte protoporphyrin, zinc
protoporphyrin
Normal increased increased
Serum transferrin receptor Normal increased increased
Reticulocyte hemoglobin content Normal reduced reduced
Hemoglobin Normal Normal Reduced
Mean corpuscular volume Normal Normal Reduced
Symptoms Fatigue, malaise Pallor, pica, in some
patients

40. Laboratory diagnosis
• Complete blood count
• Bone marrow
• Serum parameter
• ferrokinetic Studies

41. BLOOD AND
BONE MARROW FINDINGS
• BLOOD: peripheral smear findings
– microcytosis, hypochromia, anisocytosis , poikilocytosis (
eliptocytes and pencil cells

43. AUTOMATED ANALYSER FINDINGS

44. IRON DEFICIENCY ANEMIA
• MCV - Reduced ( N : 80-100 fl)
• MCH - Reduced ( N : 27-32 pg)
• MCHC– Normal to reduced (N: 30-34 mg/dl)
• Iron- Reduced (N: 4 gm )
• TIBC- Increased (N: 47-70 µmol/l)
• Transferin Saturation- Reduced (N :16-50%)
• Ferritin- Reduced (N:15–300 µg/l)
• RDW: High ( N : 11.5- 14 %)
• Reticulocytes: Normal/Low (N: 0.5- 2.5%)
• Platelates: Normal/Low/High
• WBC: Normal/Low
• Smear: Hypochromia,anisocytosis,
microcytosis, poikilocytosis

45. Bone marrow findings
• BONE MARROW
– Early stage - Normoblastic hyperplasia
– Normoblasts - smaller than normal
• deficient in hemoglobin
• Irregular shaped with frayed margins
– polychromatic and pyknotic cytoplasm of
erythroblasts is vacuolated and irregular in outline
(micronormoblastic erythropoiesis)
– absence of stainable iron
• WBCs- Giant neutrophil bands or metamyelocytes
• Storage iron is absent

46. Marrow film- Iron deficiency anemia

47. Marrow film- prussian blue stain

48. Lab tests of iron deficiency of
increased severity
NORMAL Fe deficiency
Without anemia
(prelatent)
Fe deficiency
With mild anemia
(latent)
Fe deficiency
With severe anemia
(IDA)
Serum Iron 60-150 60-150 <60 <40
Iron Binding
Capacity
300-360 300-390 350-400 >410
Saturation 25-55 30 <15 <10
Hemoglobin Normal Normal 9-12 6-7
Serum Ferritin 40-200 <20 <10 0-10

49. Methods for assessing iron status
Measurements Reference range Diagnostic Value Confounding factors
1. Hemoglobin
concentration
Male: 13–17 g/dl
Female: 12–15 g/dl
• Defining anemia and
assessing its
severity.
• Response to a
therapeutic
trial of iron confirms
iron deficiency
anaemia (IDA).
Other causes of anemia
besides iron deficiency
2. Red cell indices
Mean cell volume
Mean cell
haemoglobin (MCH)
83–101 fl
27–32 pg
Low values indicate iron
deficient erythropoiesis.
May be reduced in
disorders of
haemoglobin synthesis,
other than iron deficiency
(thalassaemia, sideroblastic
anaemias, anaemia of
chronic disease)
3. Tissue iron supply
Serum iron 10–30 µmol/l Low values in iron
deficiency, high
values in iron overload
Reduced in acute and
chronic disease; labile,
use of fasting morning
sample reduces variability

50. MEASUREMENT REFERENCE RANGE
(ADULTS)
DIAGNOSTIC USE CONFOUNDING FACTORS
Total iron binding
capacity (TIBC)
47–70 µmol/l High values -tissue iron
deficiency
Low value- iron overload
Rarely used on its own.
Reliable reference ranges
not available
Transferrin
saturation (TS)
(iron/TIBC × 100)
16–50% Low- iron deficiency
anemia
Reduced in acute and
chronic
disease
Iron supply to the bone
marrow
Serum transferrin
receptor (sTfR)
Red cell zinc
protoporphyrin
(ZPP)
2.8–8.5 mg/l
<80 µmol/mol Hb
Reduced red cell ferritin or
increased ZPP, sTfR and %
hypochromic red cells
indicate impaired iron
supply to the bone
marrow.
• Identifying early iron
deficiency and, with a
measure of iron
stores.
• Distinguishing
this from anemia of
chronic disease.
• sTfR concentration is
related to extent of
erythroid activity as
well as iron supply to
cells.
• ZPP may be increased
by other causes of
impaired iron
incorporation
into haem
(sideroblastic
anaemias, lead
poisoning,
inflammation)

51. MEASUREMENT REFERENCE RANGE
(ADULTS)
DIAGNOSTIC USE CONFOUNDING
FACTORS
Iron stores
Serum ferritin
Male 15–300 µg/l
Female 15–200 µg/l
Correlated with body iron
stores from deficiency to
overload
• Increased: as acute-
phase protein
• By release of tissue
ferritin after organ
damage.
• Decreased:
vitamin C deficiency
Bone marrow Grade • Graded as absent,
present or increased
• Used to d/b ACD and
IDA.
Adequate sample
required

52. Serum Iron
• Reference interval is 50–160 µg/dL
• Determination of iron status requires-
– Estimate of the amount of haemoglobin iron (usually by measuring the
haemoglobin concentration (Hb) in the blood).
– Level of storage iron (measuring serum ferritin concentration).
• Assay of serum iron- It is modification of method recommended by the
International Council for Standardization in Haematology (ICSH) and is
based on the development of a coloured complex when ferrous iron
released by serum protein denaturation in the presence of reducing
agent is treated with a chromogen solution.
• Alternate methods-
• 1. Microtitre plate method
• 2. Automated Methods for Serum Iron- non-precipitation method ,
available from Randox Ltd .
• INTERPRETATION
• Level reduced in - Iron deficiency anemia
– Anemia of chronic diseases
– Infections

53. Serum ferritin
• Normal value- 15–300 µg/L (Men>women)
• Water-soluble complex of iron hydroxide with the protein
apoferritin.
• It is located in cells of the liver, spleen, bone marrow .
• Ferritin assay- Immunoradiometric assay ( 1st method)
• MOA- Excess radiolabelled antibody react with ferritin and antibody
not bound to ferritin was removed with an immunoadsorbent.
• Interpretation –
• Ferritin is the basic protein which deposits iron.
• Serum ferritin concentration reflects iron reserve of individual.
• Reduced in iron deficiency anemia.
• It is acute phase reactant so raised in some hepatocellular diseases,
malignancies, and inflammatory diseases, so may give
disproportionately high estimate of storage iron .
• Age between 6 months- 15 yrs reference value is low.

54. Transferrin
• Transferrin has a very high affinity for iron at neutral pH
and iron release takes place through a specific
membrane receptor
LIMITATION
• The concentration of transferrin is subjected to the
daily variations
• Acute inflammation contributes to lowering the
transferrin level
CLINICAL SIGNIFICANCE
• Basic clinical index for the differentiation between the
iron-deficiency ([TF]↑) and hemolytic anemia ([TF]↓)
• More precise index than total iron binding capacity
• After the liberation of iron from the complex, TF ion of
Fe3+ must be restored into Fe2+

55. Serum (Total) Iron-Binding Capacity
(TIBC)
• Iron in plasma binds to transferrin and TIBC is the measure of
this protein.
• The additional iron-binding capacity of transferrin is known
as the unsaturated iron-binding capacity (UIBC).
• TIBC = UIBC + serum iron concentration .
• TIBC(µmol/l) = Transferrin conc (gm/l) × 25
• Estimation of TIBC- By adding an excess of iron to a solution
and measuring the iron retained in solution after the addition
of a suitable reagent such as ‘light’ magnesium carbonate or
an ion-exchange resin that removes excess iron.
• Principle
Excess iron as ferric chloride is added to serum. Any iron that
does not bind to transferrin is removed with excess
magnesium carbonate. The iron concentration of the iron-
saturated serum is then measured.
• Raised in iron deficiency anemia

56. UIBC DETERMINATION
• The UIBC may be determined by methods that detect
iron remaining and able to bind to chromogen, after
adding a standard and excess amount of iron to the
serum.
• The UIBC is the difference between the amount
added and the amount binding to the chromogen.
• METHODS-
– Chromogen solution
– Microtitre tray
• UIBC is being evaluated as a screening test for iron
overload in genetic haemochromatosis.

57. Serum Transferrin (Beta-globulin)
• Main function - transport of absorbed iron in the depot (liver,
spleen), into the medullary erythroid predecessors and into
the reticulocytes.
• Basic place of synthesis - liver.
• Reference interval for adults is 200–300 µg/dL (2.0–3.0 g/l )
• 1 mg of transferrin binds 1.4 µg of iron.
• ESTIMATION OF SERUM TRANSFERRIN-
• by an immunological assay-Rate immunonephelometric
methods
• INTERPRETATION
• An increase in the content of transferrin with lowering in the
level of iron of serum is characteristic for the iron-deficiency
state.
• A decrease in the level of transferrin can be with the damage
of the liver (different genesis) and with the loss of protein (for
example, in nephrotic syndrome).
• The level of transferrin is increased in the last term of
pregnancy.

58. Transferrin saturation
• The transferrin saturation is the ratio of the serum iron
concentration and the TIBC expressed as a percentage
• Normally, this is 20%–55%.
• A transferrin saturation of <16% is usually considered to
indicate an inadequate iron supply for erythropoiesis.
• Used for detection of genetic haemochromatosis.
• Normal diurnal variation serum iron is as much as 30% with
highest values in the morning and lowest values late in the
day.
• fasting morning blood specimens are preferred for the
diagnosis of iron deficiency.
• Transferrin Index
It is serum iron concentration ( µmol/l) divided by the
transferrin concentration (determined immunologically and
expressed as µmol/l)

59. SERUM TRANSFERRIN RECEPTOR
• There are two types of
transferrin receptors TfR1
and TfR2 .
• TfR1 is essential for tissue
iron delivery
• Transferrin binds to
TfR1, the complex is
internalized and iron is
released when the pH of
the internal vesicles is
reduced to about 5.5 .

60. Estimation of transferrin receptors
(TfR)
• Transferrin receptors have been purified from placenta
and from serum.
• Three enzymes immunoassay kits
• Fully automated, diagnostic, immunoassay systems .
• Four different units (nmol/l, µg/ml, mg/l and ku/l)
• INTERPRETATION
• sTfR concentrations are high in neonates and decline
until adult concentrations are reached at 17 years.
• Increased during pregnancy

61. sTfR CONCENTRATION CONDITION
Increased Increased erythroid proliferation:
Autoimmune haemolytic anaemia
Hereditary spherocytosis
ẞ Thalassaemia intermedia or major
ẞ Thalassaemia/HbE
Haemoglobin H disease
Sickle cell anaemia
Polycythaemia vera
Decreased tissue iron stores:
Iron deficiency anaemia
Normal to increased Idiopathic myelofibrosis
Myelodysplastic syndrome
Chronic lymphocytic leukaemia
Normal Haemochromatosis
Acute and chronic myeloid leukaemia
Most lymphoid malignancies
Solid tumours
Anaemia of chronic disease
Decreased Chronic renal failure
Aplastic anaemia
After bone marrow transplantation

62. Erythrocyte Porphyrins
• Protoporphyrin IX is the immediate precursor to haem.
• The enzyme ferrochelatase is able to insert ferrous iron to produce haem
or zinc cation to form zinc protoporphyrin (ZPP).
• When iron supply to ferrochelatase is limiting, ZPP increases.
• When ferrochelatase is limiting, free protoporphyrin accumulates.
• Normal reference value is adults is less than 70 µmol/mol haem.
• ANALYSIS- Two dedicated analysers are available: the Proto Fluor Z
from Helena Laboratories, Beaumont, Texas (www.helena.com) and the
ZPP 206D from Aviv Biomedical Inc
• The measurement of EP levels as an indicator of iron deficiency has
particular advantages in pediatric hematology.
• Mean ZPP values Female > Male
• Level of porphyrins in Iron def anemia according to WHO
• Children younger than age 5 years- >61 µmol/mol haem
• all other subjects, levels should be >70 µmol/mol haem.
• Erythrocyte porphyrins became elevated before the development of
anemia
• One of the earliest indicators of iron defiiency

63. Serum Transferrin Receptor–to–
Serum Ferritin Ratio (TfR/F)
• New approach to estimate total body iron
stores.
• Have limited value in identifying anemia of
chronic disease (ACD)
• Better utilized in identifying iron defiiency
anemia coexisting with ACD

64. Differential diagnosis of Microcytic
anaemia
Iron deficiency
anemia
Anemia of
chronic disease
Thalassaemia
Sideroblastic
anemia
MCV Reduced Low normal or
normal
Low Low in inherited
but normal in
acquired
Serum iron Reduced Reduced Normal Raised
Serum TIBC Raised Reduced Normal Normal
Serum Ferritin Reduced Normal or raised Normal Raised
Iron in BM Absent Present Present Present

65. Iron Deficiency in Infancy
and Childhood
• INFANTS- There are rapid changes in iron
status in the first year of life as fetal Hb is
replaced by adult hemoglobin.
• The serum ferritin concentration is a less
useful because of rapid decline in
concentration in the first 6 months and the
low concentrations generally found in children
older than 6 months of age.

66. • Children- reason for detecting iron deficiency
is to identify those who will respond to iron
therapy.
• Best predictor of response was the initial Hb,
• Serum ferritin, transferrin saturation and
erythrocyte protoporphyrin (EP) had lower
efficiencies.
• ZPP provides a useful indicator of iron
deficient erythropoiesis

67. Iron Balance in Pregnancy
Iron Fate Mean Amount (mg) Range (mg)
Lost to fetus 270 200–370
Lost in placenta, cord 90 30–170
Lost with bleeding at
delivery
150 90–310
Normal body iron loss 170 150–200
Added to expanded
red blood cell mass
450 200–600
Total 1,130 670–1,650
Returned to stores
when
450 200–600
Net loss (over 9 mo) 680 470–1,050

68. Iron deficiency in Pregnancy
• In early pregnancy serum ferritin concentrations
usually provide a reliable indication of iron
deficiency
• Haemodilution in the 2nd and 3rd trimesters of
pregnancy reduces the concentrations of all
measures of iron status.
• determination of values as ratios (ZPP µmol/
mol haem, transferrin saturation and
sTfR/ferritin) should be more reliable.

69. • In healthy women who were not anaemic and
who were supplemented with iron, serum iron,
transferrin saturation and serum ferritin fell from
the 1st to the 3rd trimester and increased after
delivery; TIBC increased during pregnancy and fell
after delivery.
• sTfR concentrations increased (approximately
two-fold) during pregnancy and this probably
reflects increased erythropoiesis.

70. CONCLUSION
• Body iron status can usually be assessed by
considering the Hb, red cell indices and serum
ferritin concentration, along with evidence of
inflammation, infection and liver disease.
•