This document discusses iron deficiency anemia, including its causes, signs and symptoms, diagnostic tests, and treatment options. Key points include: - Iron deficiency anemia results from low iron levels, reducing oxygen-carrying capacity in the blood and causing tissue hypoxia. - It has various causes including low dietary iron intake, reduced absorption, blood loss, and increased requirements during growth and pregnancy. - Signs include fatigue, paleness, and nutritional deficiencies affecting nails, tongue, and lips. Diagnostic tests include low iron saturation and ferritin levels on blood tests. - Treatment involves oral or intravenous iron supplementation, with adjuvants like vitamin C to aid absorption. Refractory cases may require alternative oral

1. Iron defciency anemia and
Recent advances in management
Chair person:- Dr Seetaram N K
Student:- Dr Md Juned

2. • Anemia is defined as reduction in total
circulating red cell mass below normal limit
• Anemia reduces the oxygen carrying capacity
of the blood leading to tissue hypoxia
• It is absolute when red cell mss decreases and
relative when plasma volume increases

3. Causes of anemia

4. Iron metabolism
• Dietary iron
• Absorbtion
• Transport
• Distribution
• Storage
• Physiologic regulation

5. • Iron is required by every cell in the body
• It has vital role in
1. Oxidative metabolism
2. Cellular growth and proliferation
3. O2 transport and storage
• Iron must be bound to protien
• Inorganic or ionic form is dangerous

6. • Iron exceeds the body capacity – toxicity
• Too littlte-- metabolic process inhibited

7. • Heme is an iron-chelated porphyrin ring that
functions as a prosthetic group (nonamino
acid component) of a protein protoporphyrin
IX,
• is composed of a flat tetrapyrrole ring with
ferrous iron inserted into the center.

9. Hemoglobin (Hb)

10. IRON REQUIREMENTS
• Requirements are determined by obligatory
physiological losses and the needs imposed by
growth.
• men require only 13 mg/kg/day (~1 mg of iron),
• menstruating women ~21 mg/kg/day (~1.4 mg).
• In the last two trimesters of pregnancy, ~80
mg/kg/day (5–6 mg),
• infants have similar requirements due to their
rapid growth.

11. DIETARY IRON
• There are 2 types of iron in the diet; haem
iron and non-haem iron
• Haem iron is present in Hb containing animal
food like meat, liver & spleen
• Non-haem iron is obtained from cereals,
vegetables & beans
• Milk is a poor source of iron, hence breast-fed
babies need iron supplements

12. AVAILABILITY OF DIETARY IRON
• Foods high in iron (>5 mg/100 g) include
organ meats such as liver and heart, brewer’s
yeast, wheat germ, egg yolks, oysters, and
certain dried beans and fruits;
• foods low in iron (<1 mg/100 g) include milk
and milk products and most vegetables.

13. Iron absorption
• Food sources supply: 10 - 25 mg / day
• Absorbed in the brush border of the upper
small intestine
• Most dietary iron is nonheme form, <5%
bioavailability
• < 10% dietary iron is heme form, >25%
bioavailability

14. Iron absorption from food
Iron Absorption (% of dose)
0 5 10 15 20 25
Veal muscle
Hemoglobin
Fish muscle
Veal liver
Ferritin
Soy beans
Wheat
Lettuce
Corn
Black beans
Spinach
Rice

15. Factors affecting absorbtion
• Type of iron:- heme iron vs non heme iron
• Gastric acid:- promote absorbtion by reducing
from ferric to ferrous form
• Reducing agents:- ascorbate, succinate, SH
group of amino acid, Fe3+ to Fe2+
• Phosphorous diet:- decrease absorbtion
• Antacids :- decrease

16. • Iron with or after food :- decrease
• Pancreatic secretion:- decrease
• Iron deficiency:- increase
• Infections and GI surgeries:- decrease

20. Iron Distribution

21. Role of Hepcidin in Iron metabolism

23. Proteins involved in iron Homeostasis
• Hepcidin
• DMT1
• Hephaestin
• Ferroportin1
• Tranferrin receptor
• HFE
• Transferrin

25. Iron transport
• Transferrin – plasma iron transporter protein.
Carries less than 1% of total body iron
• Ferritin – intracellular storage of iron
• Hemosiderin – long term iron storage pool

26. Storage of iron
• Ferritin
– multi-subunit protein
– primarily intracellular
– some in plasma
• Hemosiderin
– insoluble form of
ferritin
– visible
microscopically

27. Iron stain of bone marrow
Iron Deficient Marrow
Prussian Blue Stain
Normal Marrow
Prussian Blue Stain

32. Causes of iron defeciency

33. Signs and symptyms
• Pagophagia - craving ice
• Pica - craving of nonfood
substances
– e.g., dirt, clay, laundry
starch
• Glossitis - smooth tongue
• Restless Legs
• angular stomatitis -
cracking of corners of
mouth
• Koilonychia - thin, brittle,
spoon-shaped fingernails

35. Koilonychia:- lack of iron structural stress during
the keratinisation process of nail formation,a
difference in the angle of the distal matrix in
comparision to the proxymal matrix , a lack of
oxygen to the matrix and atrophy of the
matrix, all which would affect the shape of the
nail plate

36. Marked
hypochromasia,
microcytosis

37. Tests for Iron Deficiency
• Peripheral blood smear
• Red cell indices (MCV, MCH)
• Serum ferritin
• Serum iron / transferrin = iron saturation
• Bone marrow iron stain (Prussian blue)

38. Differential diagnosis

39. CONDITION SERUM
IRON
TIBC FERRITIN COMMENT
Iron deficiency ↓ ↑ ↓ Responsive to iron
Chronic
inflammation
↓ ↓  Unresponsive to iron
Thalassemia major ↑ N N
Reticulocytosis and
indirect
bilirubinemia
Lead poisoning N N N Basophilic stippling of
RBCs
Sideroblastic anemia ↑ N  Ring sideroblasts in
marrow

40. MENTZERS INDEX
• MCV/RBC
• >13 - S/O IRON DEFICIENCY ANEMIA
• 11-13 - INDETERMINATE
• <11 - THALASSEMIA TRAIT

41. Red cell distribution width
• RDW measures range of variation of red cell
volume
• Normal range is 11.5 to 14.5 %
• It is measure of anisocytosis
• Usually elevated in deficiency of Iron, Folate,
B12
• Usually normal in Hemoglobinopathy

42. Anaemia of Chronic Disease
• Thyroid diseases
• Malignancy
• Collagen Vascular Disease
– Rheumatoid Arthritis
– SLE
– Polymyositis
– Polyarteritis Nodosa
• IBD
– Ulcerative Colitis
– Crohn’s Disease
• Chronic Infections
– HIV, Osteomyelitis
– Tuberculosis
• Renal Failure

44. Iron deficiency in inflammation and
CKD
Transferrin sats
%
Ferritin
Inflammation <20% <100
CKD <20% <100
ESRD <30% <500

45. Erythropoeitin
• Subcutaneous administration is preferred
because absorption is slower and the amount of
• drug reqItuired is reduced by 20–40%.
• Patients are started on doses of 80–120 U/kg of
epoetin alfa, given subcutaneously, 3 times/week.
• The most common side effect of epoetin alfa
therapy is aggravation of hypertension, which
occurs in 20–30%

46. Refractory Iron Deficiency Anemia
• Failure to respond to treatment at a dose of at
least 100 mg of elemental iron per day after 4 to
6 weeks of therapy
Causes
• H pylori
• Autoimmune gastritis
• Celiac disease
• Hereditary iron-refractory iron deficiency
syndrome (IRIDA)

47. treatment
• Carbonyl iron (elemental), heme-iron polypeptide
(extracted from porcine RBC), polysaccharide-iron
complex
• Ascorbic acid increases oral iron absorption but
dose is usually not in significant quantity to make
a difference
• Phytates (cereal grains), tannins (tea) and antacid
therapy inhibit oral iron absorption

48. • The duration of treatment is depends on the rate
of recovery of Hb and the desire to create iron
stores.
• Thus, an individual with an Hb of 5 g/dL may
achieve a normal Hb of 15 g/dL in about 50 days,
• whereas an individual with an Hb of 10 g/dL may
take only half that time.
• after 3–4 months of treatment, stores may
increase at a rate of not much more than 100
mg/month.

49. Adjuvants to Iron Therapy
• vitamin C, cobalt, copper, zinc and
manganese.
• Vitamin C may increase the iron absorption
• Copper is said to mobilise iron from storage,
• cobalt is claimed to stimulate erythropoietin
production.

50. Adverse reactions to oral iron
• colicky pain,
• nausea, vomiting,
• diarrhoea or constipation,
• and gastric distress in about 6 to 12% of
individuals
• Iron in liquid form:- blackening of teeth;

51. IRON POISONING
• Most common in children
• 1–2 g of iron may cause death,
• Signs and symptoms of severe poisoning may
occur within 30 minutes after ingestion or maybe
delayed for several hours.
• They include abdominal pain, diarrhea, or
vomiting of brown or bloody stomach contents
containing pills.
• drowsiness, hyperventilation due to acidosis, and
cardiovascular collapse.

52. • concentration of iron in plasma:- <63 mm (3.5
mg/L), the child is not in immediate danger.
However, vomiting should be induced when there
is iron in the stomach,
• x-ray to evaluate the number of radio-opaque
pills remaining in the small bowel.
• plasma concentration of iron exceeds the total
iron-binding capacity >63 mm; 3.5 mg/L),
deferoxamine should be administered.
• Shock, dehydration, and aci

53. • Acute Oral Iron Poisoning:
• (a) Milk and egg yolk mixture is administered to
bind the iron.
• (b) Desferrioxamine 1-2 g IM is administered.
• (c) Gastric lavage with water containing
desferrioxamine is given initially, followed by 5-
10g of the same in 100 ml of water being left in
the stomach to adsorb any more iron.
• If desferrioxamine is not available, calcium
disodium edetate 35-40 mg/kg may be used.

54. • (d)Early replacement of body fluids and
electrolytes using isotonic saline, correction of
metabolic acidosis and hypotension by using
ringer lactate and vasopressor agents,
• (f) Diazepam to control convulsions

55. • In shock:- the drug is administered by IV
infusion: 10-15 mg/kg/hour to a maximum of
80 mg/kg in 24 hours.
• Without shock:- dose of 1-2 g every 3-12
hours; maximum dose 6 g in 24hours.

56. • The average dose for the treatment of iron-
deficiency anemia is about 200 mg of iron/day
(2–3 mg/kg/day), given in three equal doses of
65 mg.
• while small children and infants can tolerate
relatively large doses of iron (e.g., 5 mg/kg).
• The dose used is a compromise between the
desired therapeutic action and the adverse
effects.

57. • For prevention of iron deficiency in pregnant
women:- 15–30 mg of iron/d are adequate to
meet the 3–6 mg daily requirement of the last
2 trimesters.
• For treatment of iron-deficiency anemia,
• a total dose of about 100 mg (35 mg TID) may
suffice.

58. Indications for iv iron
• Severe symptomatic anemia requiring
accelerated erythropoesis
• Failure of oral iron from g.i intolerance
• Failure of oral iron due to absorption issues
 H pylori infection, autoimmune gastritis, celiac disease, gastric
bypass surgery, inflammatory bowel disease
• Cancer and chemotherapy associated anemia
• Anemia with chronic renal disease (with or
without[?] dialysis dependance)
• Heavy ongoing g.i or menstrual blood losses

59. • High molecular weight Iron Dextran is not
routinely used anymore due to a much poorer
safety profile (anaphalyctoid reactions) in
comparison to newer iron preparations
• Hemoglobin iron deficit (mg) = Body Wt x (14 -
Hgb) x (2.145)+1000

60. parenteral iron Preparations and
dosage
• (i) Iron-dextran: 15 ml vial, 50 mg of elemental
iron/ml.
• (ii) Iron-Sorbitol-Citric acid complex: 1.5 ml vial, 50
mg of iron/ml.
• For IV use:
• (i) High molecular weight iron dextran, 1-2 ml vial,
50 mg iron/ml.
• (ii) Low molecular iron dextran 2ml vial, 50 mg of
iron/ml
• (iii) Iron saccharate (Ferric hydroxide complexed
with sucrose), 5ml vial, 20 mg of iron/ml.

61. • (iv) Ferric gluconate, 5 ml vial, 12.5 mg
iron/ml.
• (v) ferric carboxymaltose, 15 ml single use vial,
50 mg iron/ml, given as 2 doses separated by
at least 7 days.
• (vi) Ferumoxytol, 17 ml single use vial, 30 mg
iron/ml, given as 2 doses separated by 2-8
days.

62. • lron-dextran It is a high molecular weight
colloidal solution containing 50 mg elemental
iron
• Route:- i.m. as well as i.v.
• By i.m. route it is absorbed through lymphatics,
circulates without binding to transferrin and is
engulfed by RE cells where iron dissociates and is
made available to the erythron for
haemesynthesis..
• dextran is antigenic:- anaphylactic reactions are
more common

63. • Test dose:- 25mg (0.5ml) gradually over 30secs
an observe for 1hr
• IM: Injectio n is given deeply in the gluteal
region using Z track technique Iron dextran
can be injected 2 ml daily, or on alternate
days, or 5 ml each side on the same day
• Intravenous: A dose of 2 ml containing 1OO
mg iron is injected per day taking IO min for
the injection. Alternatively, the total
calculated dose is diluted in 500 ml of
glucose/saline solution and infused i.v. over 6-
8 hours under constant

64. • Ferrous-sucrose This newer formulation is a
high molecular weight complex of iron
hydroxide with sucrose,
• on i.v. injection is taken up by RE cells, where
iron dissociates and is utilized.
• It is safer than the older iron dextran
• dose of 100 mg (max 200mg) can be injected
i.v. taking 5 min, once daily to once weekl y till
the total calculated

65. • Ferric carboxymaltose :-the ferric hydroxide core
is stabilized by a carbohydrate shell.
• It is rapidly taken up by the RE cells, primarily in
bone marrow (upto 80%),Iiver and spleen.
• 15ml single use vial 50mg/ml given as 2 dose
separated by atleast 7 days
• or upto I000 mg is diluted with I00 ml saline
(not glucose solution) and in fused i. v. taking 15
min or more.
• It should not be injected i.m.

66. • it has caused a rapid increase in haemoglobin
level in anaemia patients and replenished stores.
• The incidence of acute reaction is very low.
• Headache, nausea, abdominal pain are generally
mild.
• Hypotension, flushing and chest pain are
infrequent.
• Due to lack o f safety data, it is not recommended
for children < 14 years.

67. Lmw Iron
Dextran
Iron Sucrose Ferric
Gluconate
Ferumoxytol Ferric Carboxy
maltose
Administered
Dosage
100mg 200 mg 125 mg 510mg 750mg
Total Dose
Infusion
1000 mg no no 1020 mg 3d
apart
1500mg 7d
apart
Cost Inexpensive Inexpensive Inexpensive Expensive Expensive
Indication IDA IDA in CKD IDA in
CKD/HD
+epo
IDA in CKD IDA
+
IDA in CKD
Test dose Yes none none None None
Administratio
n
Iv
(preferred)
or im
Iv push or
15m
infusion
i.v push or
1hr infusion
17s i.v push or
15 m infusion
7.5 m iv push or
15 m infusion

68. Response to oral Iron Therapy
• Peak reticulocyte count 7 - 10 d.
• Increased Hb and Hct 14 - 21 d.
• Normal Hb and Hct 2 months
• Normal iron stores 4 - 5 months

70. References
• Harrison 20th edition
• Clinical laboratory hematology Shirlyn B.
McKenzie 2nd edition
• Wintrobes clinical hematology 14th edition
• Goodman and gilman’s 13th edition