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ANEMIA IN PREGNANCY IDA: CHANGING CONCEPT
Dr Veena Agrawal
M.S., MICOG, WHO Fellow (USA)
Professor & HOD, Obst. & Gynecology,
G. R. Medical College
Core faculty of human Genetics,
Jiwaji University
Gwalior, M.P.
Dr Sonali Agrawal
DGO
Consultant Agrawal Hospital & Research Centre
Gwalior, M.P. India
Anemia is a sign, not a disease
of dynamic process
World Health Organization
 Anemia – a major killer
 Incidence is about 50% in general population, (in
India 80%).
 Iron deficiency anemia is the most common
medical disorder during pregnancy.
 In pregnancy, it is one of the leading causes of
maternal mortality in developing countries.
 It affects both mother and fetus.
PREVALENCE OF anemia in
India
Available studies on prevalence of nutritional anemia
show that:
 65% infant and toddlers,
 60% 1-6 years of age,
 88% adolescent girls (3.3% has hemoglobin <7 gm./dl;
severe anemia) and
 85% pregnant women (9.9% having severe anemia)
 prevalence higher in lactating than pregnant women
The most common is iron deficiency anemia.
Causes:
 Physiological - disproportionate ↑se of plasma
volume apparent reduction of RBC, Hb & Hct.
Picture is normochromic normocytic.
 Acquired:
 Nutritional
 Iron deficiency anemia (60%),
 Macrocytic anemia (10%) due to def of folic acid
and/or vitamin B12
 Dimorphic and protein deficiency anemia (30%) in
extreme malnutrition
Causes of Anemia
 Hemorrhagic
 acute blood loss,
 chronic (hook worm, bleeding piles)
 Infections
 Acute (e.g., malaria)
 Chronic (e.g., tuberculosis)
 Genetic conditions (e.g., thalassemia, sickle cell)
 Enzyme disorders (e.g., sideroblastic anemia)
 Anemia of chronic disease (e.g., malignancy, chronic
renal failure
Criteria for Physiologic Anemia
 Hb: 10gm%
 RBC: 3.2 million/mm3
 PCV: 30%
 Peripheral smear showing normal morphology of
RBC with central pallor
Significance of Hypervolemia
1. To meet the demands of the enlarged uterus
with its greatly hypertrophied vascular system.
2. To protect the mother, and in turn the fetus,
against the deleterious effects of impaired
venous return in the supine and erect positions.
3. To safeguard the mother against the adverse
effects of blood loss associated with parturition.
IDA
 12th most important risk factor for all mortality
globally.
 9th most important risk factor for the global burden of
disease.
 associated with 115,000 of the 510,000 maternal deaths
(22%) and 591,000 of the 2,464,000 perinatal deaths
(24%) occurring annually around the world.
Mason, Rivers and Helwig Food and Nutrition Bulletin 26: 57-162, 2005..
 1/3 world’s population suffers from anemia, mostly
iron deficiency anemia.
 India continues to have a very high prevalence.
 National Family Health Survey (NFHS-3) reveals the
prevalence of anemia to be 70-80% in children, 70% in
pregnant women and 24% in adult men.
Definition of Anemia in Pregnancy
 WHO-Hb conc <11gm/dl & Hct < 33%
 CDC definition-Hb con <11gm/dl & Hct < 33% during
the 1st trimester & < 10.5 gm/dl Hct < 32% during the
2nd trimester
 Absolute iron deficiency is defined as ferritin <200
µg/L with or without iron saturation <20%,
CDC definition:
Pregnancy
Trimester
Hemoglobin
Hematocrit
First
11.0
33.0
Second
10.5
32.0
Third
11.0
33.0
Factors required for erythropoiesis
• Proteins (erythropoietin)
• Minerals (iron)
• Trace elements: (Zinc, Cobalt, Copper etc)
• Vitamins: Folic acid, Cyanocobalamin (B12), Vitamin C, Pyridoxine
(B6), Riboflavin, Vitamin A
• Hormones: Androgens & Thryoxine
Letsky E. 1995
Prasad AS. J. Am. Coll. Nutr. 1996
Anemia
 Acc to ICMR
 Mild
10-11mg%
 Moderate
7-10.9mg%
 Severe
4 - 6.9mg%
 Very severe <4mg%
Iron
depletion
Iron
deficient
erythropoiesis
Iron
deficiency
anemia
2-3+
0 trace
0
0
Plasma ferritin (µg/l)
100±60
< 20
10
<10
Transferrin saturation(%)
35±15
Normal
Normal
Microcytic
hypochromic
Iron absorption
Normal
±
Normal
Storage iron
Transport iron
Erythorin iron
Marrow iron
+
+
Normal Levels
Hb
13.5 – 14 gm %
R.B.C.
4.5 – 4.7 million/cu mm
Serum Iron
50 – 150 μgm / dL
TIBC
300 – 360 μgm / dL
Transferrin saturation
25 – 50 %
S. Ferritin level
30 μg / Lit
Red Cell protoporphyrin
30 μg / dL
Erythropoietin
15.20 U / Lit
MCV
76 – 100 L
MCH
27 – 33 pg
MCHC
33.37 gm / dL
PCV
32 – 40 %
Requirement of Iron
IRON in mg THAT SHOULD be
ABSORBED DAILY
ADULT FEMALES
MENSTRUATION
2.8
PREGNANCY(1st HALF)
0.8
(2nd HALF)
3.5
LACTATION
2.4
POSTMENOPAUSE
0.7
Iron Requirements in Pregnancy
Amount
mg
Total cost of pregnancy
Fetus
270
Placenta
90
Expansion of red blood cell mass
450
Obligatory basal losses
230
Sum
1040
Maternal blood loss at delivery
150
Total cost
1190
Net cost of pregnancy
Contraction of maternal red blood cell mass
-450
Absence of menstruation during pregnancy
-160
Subtotal
-610
Net cost
580
Normal Iron Requirements
 Iron requirement for normal pregnancy is 1gm
200 mg is excreted
300 mg is transferred to fetus
500 mg is need for mother
 Total volume of RBC inc is 450 ml
1 ml of RBCs contains 1.1 mg of iron
450 ml X 1.1 mg/ml = 500 mg
 Daily average is 6-7 mg/day
Early
Pregnancy
2.5 mg. / day
20 – 32 weeks
32 – 40 weeks
5.5 mg. / day
6.8 mg / day
 Overall needs are about 2 to 4.8 mg iron/day.
 Must consume 20 to 48 mg of dietary iron to absorb
this quantity of iron daily.
 Average vegetarian diet provide 10-15 mg iron/day.
 Amount of iron absorbed from diet+iron mobilized
from stores, is usually insufficient to meet the
demands.
 Therefore, iron supplementation during pregnancy is
recommended universally even in non anemic women.
Maternal Anemia:
A Preventable Killer
Increased
requirements
Decreased
absorption
Causes of
IDA
Increased
blood loss
Poor diet
Anemia: Etiologies
 Inadequate dietary intake
 Inadequate GIT absorption
 Poor nutrition
 Malabsorption syndromes
 Chronic alcoholism
 Certain drugs/foods
 Decreased consumption of
animal protein and ascorbic
acid
 Increased iron demands
 Blood loss
 Hookworm infestation
 Malaria
 Bleeding piles &gums
 Multiparity
 Surgery
 Diarrhea, HIV/ AIDS and
 Gastrointestinal bleeding
 UTI
 Trauma
 Recurrent Infections-
 Dialysis
Tuberculosis, Amoebiasis ,
Giardiasis, Roundworm
 other infectious diseases
Low Iron Intake or Low Iron Absorption
Haemolysis due to malaria
worm infestations (hookworm)
Multiparity
Effects of Anemia on Pregnancy
Pathophysiology - Fetus
Fetal Effects
 Mild and moderate anemia may not show significant
effects.
 Iron is actively transported across the placenta.
 Fetal iron and ferritin levels > maternal levels 3 times
Effects of Anemia on Fetus
• PROM,
• IUGR,
• IUFD,
• Prematurity,
• Abnormal trophoblast invasion
• Fetal programming & disease of newborn:
behavioral abnormalities, poor performance on Bayley
Mental Development Index, decreased cognitive function.
• Neonatal anemia
• Adult HT associated with low birth weight & high ratio of
placenta to birth weight.
•(Barker DJP, Bull AR, et all BMJ 1990; 301:259-262)
• If maternal oxygenation is 98 – 100 %,
• The fetus gets around 70 % of O2, with fetal Hb.
Fetus can compensate.
• As the maternal Hb. drops, fetal hypoxia
develops, which leads to stimulation of fetal
erythropoiesis
• Increased viscosity of blood due to raised PCV.
sluggish circulation
• End artery thrombosis
• Failure of the organs, supplied by these vessels.
 Increased PCV
 Brain damage
 Necrotising enterocolitis
 Hypoglycemia
 Hypocalcemia
 Hyperbilirubinimia
 RDS
At Birth Hb – 18 to 20 gms %,
PCV – 55 to 60 %
Severe Anemia
Fetal hypoxia
Prolonged period
Short duration
Neurological
deficit
IQ less, slow
learner
Fetal hypoxia leads to an increase in the cord blood EPO.
Cord blood EPO correlates with perinatal brain damage.
Abnormal trophoblast invasion and
release of hypoxic inducible factor
Early anaemia during
gestation
Release of placental stress hormones
(CRH,Nor epinephrine)
Fetal release of ACTH
and cortisol
Production of uterine contraction
stimulating hormones
(estrogen, connexin) and inhibition of IGF,
an anabolic hormone
Maternal Effects of Anemia
• Behavioral changes,
irritability.
• Loss of appetite,
indigestion, etc. due low
performance of each
organ.
• Increased morbidity and
mortality due to PIH, APH,
PPH, if associated.
• C CF at 30-32 wks, intrapartum & post-partum.
 Reduced immune function


•
•
•
•
- infection, ante-partum
and puerperal sepsis.
Negative thermoregulation
Increased risk of blood
transfusion
Preterm Labor
Sub involution
Failing lactation
Pulmonary Venous:
thrombosis & embolism,
due to thrombophlebitis.
ANTENATAL CARE
As a routine - No difference
Registration
Counseling
Regular check up weight, B.P., Hb%, urine
Prevention of complications
Immunizations
Care in addition to routine ANC
 H & P of Anemia
 Investigate for
 Grade of anemia
 Type
 Severity of IDA
 cause
 Tx of anemia
 Tx the cause of anemia ie. deworming, Antimalarial
Intrapartum Management
if patient comes in labor
 Individuals who MUST present in labor room
 Skilled Birth attendant's
 Anesthesiologist
 Pediatrician
 Nursing Staff
 “Extra Hands”
 Informed consent
Things that should be available:
 US Machine
 Cardiotocographic machine
 Blood transfusion facility
 Neonatal resuscitative measures
Things that should be done:
 IV Line should be patent
 Bl arranged - PCV
 Monitor pt for sign of CCF esp. immediately
postpartum
 Early cord clamping
 No methergin
 Cut shirt 2nd stage labor
 IV Diuretic
 Antibiotics
Postpartum Management
 Monitor patient for sign of CCF
 Antibiotics
 Otherwise same
Clinical Feature of Anemia
Symptoms:
 Mild anemia; usually asymptomatic
 Moderate anemia - weakness, fatigue, exhaustion, loss of
appetite, indigestion, giddiness, breathlessness
 Severe anemia-palpitation, tachycardia, breathlessness,
Increased cardiac output, CHF, general anasarca,
pulmonary edema
Sharma J.B. Progress in Obst. & Gynae. (Studd) 2003.
Clinical Features of Anemia
Signs:
 Pallor
 Nail changes – Koilonychia
 Angular cheilosis, Glossitis, Stomatitis
 Oedema
 Hyperdynamic circulation (short and soft systolic murmur)
 Fine crepts
Sharma J.B. Progress in Obst. & Gynae. (Studd) 2003.
 What is level
 Type
 cause
Anemia?
Production?
Survival/Destruction?
The key test is the …..
The Reticulocyte Count
(Kinetic Approach)
 ↑ reticulocytes (>2-3% or 100,000/mm3 total) are seen in
bl loss and hemolytic processes, although up to 25% of
hemolytic anemia's will present with a normal count.
 Hb Measurement & Haematocrit
 Peripheral smear will often reveal many diagnostic clues
 Reticulocyte count
 Serum ferritin most sensitive tool. Values < 10mcg/L indicate
absence of stored iron, <20 or <15 µg/L indicate depleted iron stores
 Transferrin saturation (TSAT), should be above 16% with normal
being 30%
 Soluble serum transferrin receptors (sTfR) (>45 nM/Ldenote IDA),
TSAT <20%, serum ferritin <100 ng/mL & % of
hypochromic RBC’s >10% indicate absolute ID,
 RBC indices - little diagnostic value unless the MCV is
below 70fl
 Serum iron - decreased in a variety of states including
iron deficiency, inflammation & stress. Varies
tremendously from morning to evening and from day to
day. value < 0.5mg/L indicate anemia, normal range
:0.80 to 1.80 mg/L
 Total iron binding capacity is very specific for iron
deficiency (near 100%) but has poor sensitivity (<30%).
 Iron saturation (Fe/TIBC x 100) can be decreased below
16% in both anemia of chronic disease and iron
deficiency
Tests used in Diagnosing Iron
Deficiency Anemia (IDA)
Test
Limitations
*Blood smear hypochromia
Subjectivity
*MCV
Insensitivity
RDW
Non-specificity
Serum iron
Markedly lowered by fever or
inflammation
Iron binding capacity (IBC)
Moderately lowered by fever; increased
by pregnancy
Iron/IBC (% saturation)
Like serum iron, lowered by fever
*Ferritin
Mildly raised by fever or inflammation
Stool for occult blood
Bleeding may be intermittent
Bone marrow for iron stores
Expensive and invasive; iron depletion
does not prove IDA
Specific tests for etiology of the anemia
•Urine & stool examination
• Test for malaria
• Rarely- Endoscopic or barium studies of the GI
tract, bone marrow examination
Exclude other causes of hypochromic microcytic
anemia
•Anemia of chronic disease
• Thalassaemia trait
• Sideroblastic anemia
Lab Testing for
Iron Deficiency Anemia (IDA)
Patient with anemia,
Check ferritin, Iron, IBC level
Ferritin
> 100
Ferritin
20-100
sTR
<45
Ferritin < 20,
or Iron < 50
and IBC > 450
sTR
>45
IDA
Iron
therapy
Ferritin > 20,
or Iron > 50
and IBC < 450
Workup for other
causes of anemia
Look for
source of
blood loss
Prevention
 Dietary modification
 Iron supplementation of adolescent & non pregnant






female
Tx of Hookworm infestation
Control of malaria
Iron supplementation in pregnant Women
Food fortification
Antenatal care for early recognition
Optimal birth spacing
Eat foods that are:
 Rich in iron - liver, beef, whole-grain breads
 cereals, eggs, dark green vegetables and dried fruit.
 High in folic acid, such as wheat germ, beans,
peanut butter, oatmeal, mushrooms, collards,
broccoli, beef liver and asparagus.
 High in vitamin C, such as citrus fruits and fresh,
raw vegetables. Vitamin C makes iron absorption
more efficient.
 Take prenatal vitamin and mineral supplements,
especially folic acid.
Diet
Low Bioavailability
Rice, Wheat
Maize
Potato
High Bioavailability
Eggs
Fish
Meat
Dietary Components and Absorption of Iron
Dietary components
Absorption
Calcium (Dairy products)

Meat, fish, poultry, sea-food
Phytate (grain products)


Polyphenols

(Tea, spices, vegetables)
Vitamin C

Depends upon severity
and gestation
Which Iron Compound?
Inorganic
1. Ferrous
•
sulfate, fumarate, gluconate, ascorbate, succinate,
glutamate, dextran, carbonyl iron, and lactate
•
bis-glycinate chelate.
2. Ferric Salts – iron (III)-hydroxide polymaltose
complex
Organic - Heme
Ferrous vs. Ferric iron

Ferrous iron is absorbed three times more than ferric iron.

Ferric iron absorption is dependent on duodenal ferric
reductase.

Availability of duodenal ferric reductase is dependent on
ascorbic acid.

Supplementation of ascorbic acid may increase ferric iron
absorption.
First iron pills were commonly known as Blaud's
pills, which were named after P. Blaud of Beaucaire.
He is a French physician who introduced and started
the use of these medications as a treatment for
patients with anemia.
Goal:
 Hgb – 11-12g/dL
 Hct – 33 – 36%
Iron Preparations
 Available with various amounts of iron, iron salts,
complexes, combinations, and dosing regimens.
 Available in tablets and capsules, liquid and drops,
coated and extended release tablets and capsules.
• Different oral preparations exhibit different safety profiles.
• Greater oxidative stress is observed with oral iron (II)
•
•
•
•
salts than with iron (III) complexes
Iron salts are selected based on compliance of the
tolerance, side effects, clinical situation of the pt and
availability of a particular salt.
Fe sulphate is cheapest, best absorbed, and most
commonly prescribed, showing a rapid rise in both serum
iron concentrate and NTBI (Non transperrin bound iron) &
greatest frequency of adverse events
If not tolerated, then ferrous gluconate, fumarate and
others are the next choice.
Oral iron must be continued for 3-6 mon after Hb has
come to normal levels – for building iron stores.
“In small intestine ferric iron is precipitated
as ferric hydroxide which is basically RUST”
“The difficulty of absorbing rust is the main
reason for the prevalence of iron deficiency
anemia in the world”
“The most readily available and cheapest
natural reducing agent is ascorbic acid”
Iron metabolism
Iron Supplementation During Pregnancy
In developed countries like U.K., routine Iron
supplementation is not recommended.
However, it is mandatory in non-industrialized countries.
WHO - 60 mg elemental iron with 250 mg folic acid for 6
months in pregnancy and additional 3 months postpartum.
NNACP in India - 100 mg of elemental iron and 500 mcg of
folic acid for 100 days after the first trimester
Ferrous Salts or Bivalent Iron Salts

Good bioavailability however, decreases in the presence
of dietary inhibitors like phytates, tannic acid, etc.

Efficacious and cheap

Several disadvantages:
 High incidence of GI Tract side effects (~23 %).
 Teeth staining with liquid preparations
 Salty astringent taste which is not palatable for most
children
Side Effects of Oral Iron
Nausea
Vomiting
Constipation
Abdominal cramping
Diarrhea
The tab can be given with meals or
different brands may be tried.
Ways to Minimize Adverse
Effects of Oral Iron
 Recommend half the dose and gradually ↑se to the
full dose.
 Take the supplement in divided doses.
 Take with food to alleviate GIT distress (↓se iron
absorption by as much as 40-66%).
 Change to a different iron preparation.
 Concomitant use of a stool softener, such as
docusate, may help alleviate constipation.
Factors that Affect Absorption
 ↓ as doses get larger - supplement in 2 or 3 divided doses.
 Enteric-coated and long-acting supplements may be ineffective. not




dissolve in the stomach hence not absorbed in duodenum or upper
jejunum
Ascorbic acid is enhanced absorption by forming a chelate with ferric
iron at acid pH that remains soluble at the alkaline pH of the
duodenum. & reverse the inhibiting effects of substances such as tea
and calcium.
Taken with food decreased absorption by as much as 40-66%.
Food ↓ absorption- Tannins from foods, such as tea
Iron forms an insoluble complex with several other drugs - decreased
absorption of both iron and the other drugs, e.g. tetracycline,
pencillamine, methyldopa, levodopa, bisphosphonates quinolones,
calcium and antacids, phosphates, etc.
Effectiveness of Iron Supplementation
 Clinical improvement
 laboratory indices
 Reticulocyte count
 Hemoglobin
 Ferritin levels
 TAST
 Newer measurements:



Reticulocyte hemoglobin content
Percent hypochromic RBCs
Soluble transferrin receptors (sTfR)
 Reticulocytosis occurs within 7-10 days after
initiation of iron therapy.
 Hb usually ↑es within 2-3 wks of starting Iron
 Therapeutic doses should ↑se Hb 0.7-1.0 g/dL / wk.
 Serum ferritin level is a more accurate measure of
total body iron stores.
 Adequate iron replacement has typically occurred
when the serum ferritin level reaches 50 µg/L.
Reasons for Failure to Respond
1. Non compliance
2. Concomitant folate deficiency
3. Continuous loss of blood through hookworm infestation or
bleeding hemorrhoids
4. Co-existing infection
5. Faulty iron absorption
6. Inaccurate diagnosis
Non iron deficiency microcytic anemia
a. Thalassaemia
b. Pyridoxine deficiency
c. Lead poisoning
d. Sideroblastic anemia
e. Atransferrinemia
Prema K. Obst. & Gynaecol 1992
Sharma JB, In Progress in Obst. & Gynaec,
2002
Foods and Drugs that Impair
Oral Iron Absorption
 Taking oral iron with food reduces absorption
 Caffeinated beverages, (especially tea)
 Calcium containing foods and beverages
 Calcium supplements
 Antacids
 H-2 receptor blockers
 Proton pump inhibitors
3 months postpartum to replenish the iron
stores
Follow up:
 Iron status (ferritin, TIBC, & TSAT) and RBC indices
must be checked periodically to re-evaluate the pt's
need for additional iron supplementation.
 Parenteral iron should not be administered to
patients with ferritin > 800 ng/mL or transferrin
saturation > 50%.
Parenteral Iron Therapy
Indicated:
 when unable to take iron due to side effects
 Non compliant
 Suffers from inflammatory bowel disease
 Near term
 With chronic renal disease
 Postpartum, especially in those who have had
significant blood loss at delivery
 Pre – post operative anemia can also be cured
Its main advantage is certainty of administration
Rise in Hb is similar to oral iron (up to 1gm per wk)
Postpartum
 High EPO state in postpartum anemia
 IV iron supplementation in such period ↑es the
erythropoiesis 5 times
 The Hb rise will be evident in as early as 5 days
Harrisons principles of medicine
Contraindications:
 Hypersensitivity to any of the Parenteral iron
products
 Liver disease or acute renal failure, Nephritis,
 Cardio respiratory disease
 Pts with ferritin > 800 ng/mL or transferrin saturation
> 50%.
Disadvantages








Pain
Nausea vomiting, headache
Skin discoloration
Abscess formation
Fever
Lymphadenopathy
Allergic reaction
Anaphylaxis
Precaution
 Oral Iron to be suspended 48 hours before parenteral
therapy.
 Emergency measures like injection hydrocortisone
adrenaline, oxygen cylinder etc., should be kept
ready.
 Look for a reaction while giving infusion.
Parenteral Iron Preparations
 Iron- sorbitol -citric acid complex (jectofer (1.5ml) 75mg –






Available in Europe, Asia & Canada. It is not yet
approved by US FDA. IM use only
HMW Iron Dextran – both IM & IV use
LMW Iron Dextran - both IM & IV use
Sodium ferric gluconate – IV use only
Iron sucrose - IV use only
Ferric carboxymaltose - IV use only
Newer
 Iron isomaltoside 1000 - IV use only
 Ferumoxytol - IV dose of 510 mg, followed by 2nd dose 3–8
days later. (Undiluted, at a rate of 1 ml/second (30
mg/sec)).
Classification of IV Iron Carbohydrate
Complex Preparations (Geisser )
TYPE I
Example Ferric
carboxymalt
ose
Iron dextran
TYPE II
TYPE III
TYPE IV
Iron
sucrose
Sodium
ferric
gluconat
e
Iron(III)-citrate
Iron(III)-sorbitol
Iron(III)-citrate +
iron(III)sorbitol + iron dextrin
Sodium ferric gluconate
+
iron sucrose
HMW ID
LMW ID
Iron
Saccharate
Ferric
Gluconate
Type of iron
complex
IronIIIdextran
IronIIIdextran
IronIIIsucrose
IronIIIgluconate in
sucrose
Mg iron per
ml
50 mg/ml
50 mg/ml
20 mg/ml
12.5 mg/ml
Preservative
No
No
No
Yes, 9 mg of
benzyl alcohol
per ml
Relative
stability of
iron complex
Robust/
strong
Robust/
strong
Half robust/
medium
strong
Weak/labile
HMW ID = high molecular wt iron dextran;,LMW ID = low molecular wt iron dextran;
TDI = total dose infusion.
HMW ID
LMW ID
Iron
Saccharate
Ferric
Gluconate
pH
4.5 - 7.0
5.2 - 6.5
10.5 - 11.1
7.7 - 9.7
T½
9.4 - 87.4 hr.
(average 58.9
hr.)
5-20 hr.
6 hr.
1 hr.
Standard
dosage
100 mg
100 - 200 mg
125 mg
5-10 min
10 min
200 mg
125 mg
Injection time
2 min
for undil. adm.
Maximum
single dose
100 mg
100 - 200 mg
2 min or
10 min
20 mg/kg
body weight
Infusion
2 min
time/Injection
undil. adm.
time.
4-6 hrs. adm.
10 min undil.
adm.
10 min undil.
adm.
TDI adm.
possible
Yes
No
No
Yes
 Complex stability:
 Iron dextran > iron sucrose > iron gluconate
 Strongest iron complexes allow for the largest dose
of iron in one infusion.
 Toxicological potential
 Iron sucrose > iron gluconate >> low Mw iron dextran
Fe-carbohydrate agents mix with plasma, enter the RES directly from
intravascular fluid compartment
Within Phagocytes of RES,Fe released from the iron-carbohydrate compound into an
LMW iron pool
LMWFe either is incorporated by ferritin into intracellular iron stores or
released from the cell to be taken up by the extracellular iron-binding protein transferrin.
Transferrin delivers iron to transferrin receptors on the surface of erythroid
precursors.
Transferrin delivers iron to transferrin receptors on the surface of erythroid
precursors.
Iron-transferrin-transferrin receptor complex supplies Fe for Hb synthesis &
maturation of the red cell
Safety Profile
 Most of the iron is deposited in the Reticulo-endothelial
system than in parenchyma.
 This gives the advantage of not having free-radical
induced lipid peroxidation which takes place within
parenchyma only.
 Practically no liver injuries occur as confirmed by
experimental histological results.
 Iron dextran has the highest incidence of modest and
severe life-threatening side effects.
Hypersensitivity Reactions:
 Anaphylactic reactions
 Almost exclusively with iron dextran, independent of
dose - 0.6 to 0.7%
 Mechanism is unknown but some possibilities are:
 Dextran itself is immunogenic, cause allergic reactions
including anaphylaxis & anaphylactoid reactions,
 Availability of free iron after administration.
 Antidextran antibody mediated mast cell activation
 Alternate pathway complement activation
 Direct stimulation of mast cell degranulation
.
Controversies severe adverse allergic
reactions with iron dextran
 component but other formulations are also not safe
 Pts with a h/o of allergy may be at risk of developing
undesired immunological reactions such as asthma
(Meyler 14th edition, page 701).
 Iron toxicity is more if amount of free iron released into
plasma exceeds plasma iron-binding capacity (more
likely to occur when using iron sorbitol – citric acid
complex, since the iron is less firmly bound than with
iron dextran (Meyler 14th edition, page 701).
Conditions associated with low ironbinding capacity of parentral iron- More
reaction
 Malnutrition & previous or simultaneous oral iron
therapy
 Folic acid def - likely mechanism - disturbance of iron
utilization. (Side Effects of Drugs, Annual 9, 516).
 Different parenteral iron differ experimentally in their
comparative toxicity related to free radical generation
& severe ATP depletion. Iron sucrose has greater
potential for this than iron dextran (Zager et al, 2002).
 Both Iron gluconate & sucrose are associated
with anaphylactoid type reactions, dose related.
 Reactions were due to over saturation of the
transferrin molecule resulting in the circulation of
free iron.
 This theory is still uncertain.
 Iron sucrose is also associated with
anaphylactoid type reactions, but these seem to
be dose related
 Reactions that occur are due to over saturation
of the transferrin molecule resulting in the
circulation of free iron
 This theory is still uncertain
How to give
 IM
 Intravenous Iron Therapy


IV PUSH in divided doses
 Diluted
 Undiluted
TDI
 Parenteral Iron Therapy (IM or IV) with recombinant
human erythropoietin (rHuEPO)
How to Calculate TDI:
 Total dose of infusion of iron is calculated as:
 (15- pt s Hb%) x body wt in Kg x3 = Fe in mg.
 Ganzoni Equation
Total Iron Deficit = Weight {kg} x (Target Hb
– Actual Hb) {g/l} x 2.4 + Iron stores {mg}

{ 500 if W > 35kg }
{ 15 mg/kg if W < 35kg }
Dosage Intramuscular Iron

100mg/d, Max 200mg/d can be given on D 1, 3 & 5
Z shaped deep IM to avoid skin staining.

2 High doses of IM injection 250mg each at monthly with
injection T.T has been recommended in moderate anemia
of pregnancy.
Dosage IV Iron
 Divided doses (IV Push) - dosing frequency
 Iron dextran agents, plasma half-lives - 30 to 60 hrs,
every 2 to 7 days, (once to thrice weekly).
 Ferric gluconate and iron sucrose, with 1- & 8-h halflives, respectively, could be given as frequently as
every 24 hours.
 Total Dose infusion
INTRAVENOUS IRON THERAPY
 Iron Dextran –
 Test dose (25 mg Fe) is required. Diluted in 50-100 mL of
NS and infused over 15-20 minutes.
 Monitor HR, RR, & BP q15 min for 1-2 hrs after test dose.
 Total Fe (dose) administered


as one large dose (diluted in 500-1000 mL NS and infused over 4
to 8 hrs,
or divided into many smaller doses given 1-3 times per week.
Each 100-mg dose may be administered undiluted as iv push or
100-mg dose is diluted in 250 mL NS and infused over 30-60 min.
Adverse Reactions
 Increased incidence with TDI.
 Onset is 24-48 hrs after administration.
 Effects subside within 3-4 days.
 Dose related:
 arthralgia, backache, chills, dizziness, moderate to
high fever, headache, malaise, myalgia, N/V.
 Non-dose related:
 Hypersensitivity reactions characterized by
anaphylactic shock, CV collapse, cardiac arrest,
bronchospasm, oral or pharyngeal edema, or
dyspnea.
Iron Sucrose and Iron Gluconate
 0.3% side effects with iron gluconate —very low
 Pts who had a reaction to iron dextran are more likely to




have a reaction to iron gluconate than to iron sucrose.
Adverse reactions with iron sucrose or gluconate seen at
higher doses only.
No anaphylactic death from either preparation in 35 yrs.
used in similar total doses per course of therapy,
generally 1 gm/course.
Iron sucrose may be given at 500 mg/4 hours; iron
gluconate can only be given at 300 mg/4 hours.
Iron Sucrose
 No test dose is required.
 May be administered
 as iv push undiluted at the rate of 1 mL/min. 100 mg. 200 mg over 10 min.
 Or 5-mL vial diluted in a max 100 mL NS (final conc =
1mg/mL) and administered over at least 20 min.
 200-300 mg infused over 2 hrs have been used
safely.
 Doses as 500 mg have been infused in a single 2hour session. This rate was associated with higher
incidence of side effects such as nausea,
hypotension, dizziness, and lower-back pain.
Adverse Reactions
 Experienced in > 5% of patients:
 Hypotension
 Cramps/leg cramps
 Nausea
 Headache
 Vomiting
 Diarrhea
Precautions
 Iron overload or infusing too rapidly can cause:
 hypotension, headache, N/V, dizziness, joint aches,
paresthesia, abdominal & muscle pain, edema, & CV
collapse
 Tx - IV fluids, hydrocortisone, or antihistamines
 or slow down rate of infusion
Iron gluconate
 No test dose is required.
 Administered in:
 Small installments of 125 mg Fe or less diluted in 100
mL of NS and infused over 60 min.
 Or undiluted as a slow IV injection at a rate not
exceeding 12.5 mg/min (1 mL/min).
Adverse Reactions
 Hypotension/flushing
 Associated with rapid administration
 Not associated with hypersensitivity reactions
 Resolves within 1-2 hours
Precautions
 Iron overload due to accumulation of iron in storage
sites.
 Serum iron > 300mcg/dl with transferrin saturation
may indicate overload.
 Symptoms: abdominal pain, diarrhea, vomiting
leading to pallor or cyanosis, lassitude, drowsiness,
hyperventilation due to acidosis, and CV collapse.
IV IRON POLYMALTOSE
 500mg in 200mls 0.9% NS.Run at 40ml/hr for 30
minutes, then 80mls/hr.
 Or 1000mg in 200mls 0.9% NS.Run at 20mls/hr for
30 minutes, then 45mls/hr.
 First 30 minutes will always be run as a test dose.
 Monitor reaction to medication:
 Headache, hypotension, joint/muscle pain,
tachycardia, syncope, nausea and vomiting,
circulatory collapse.
 Delayed reactions may include:
 Dizziness, syncope, stiffness (myalgia of
legs/hands/face)
 Chest pain/back pain
 Rash
Laboratory Testing after IV
 Iron-carbohydrate compounds interfere with clinical
laboratory determination of serum iron
 Serum iron & transferrin saturation should be tested
after most or all of the IV iron agent has been
cleared.
 No earlier than 7 days after administration of a 100-mg
dose of iron dextran,
 2 wk after a 500-mg dose of iron dextran, and
 24 to 48 hrs after a 125-mg dose of ferric gluconate or
a 100-mg dose of iron sucrose.
 One month for ferritin or iron studies after a 500-mg
dose of Polymaltose
Dosage regimen Erythropoetin
 Inj erythropoetin - Sc or iv 100-150 iu/kg
On day 1, 3 & 5 along with parenteral iron or day 1, 3
& 5 6000units s/c erythropoetin and iron dextran
100mg deep im daily for 5 days.
 First dose after subcutaneous sensitivity test.
 Adrenaline, hydrocortisone injection oxygen to be
kept ready.
 Produces 3gm % rise in Hb over a 2wk period
Inj erythropoietin 18000u s/c in one dose & inj low
molecular dextran 500mg to be dissolved in 500ml
of dextrose to be given over 2 hours, as slow iv
Indication of Erythropoetin
 Used in severe anemia & renal failure for significant
increase in Hb and to avoid Blood transfusion.
 Gynaecological surgeries: preop use of erythropoietin
and Parenteral iron has shown to avoid the need for
blood transfusion later.
World Health Organization
‘Transfusion should be prescribed
ONLY for conditions for which there
is NO OTHER TREATMENT’
Blood Transfusion:
• Indications• Severe Anemia in third trimester, CCF in pregnancy,
Acute hemorrhage or hemolysis in pregnancy.
• Jehovah’s Witness who refuse blood transfusion due
to religious beliefs.
• S/E of BT• HIV, Hepatitis B, C, malaria, rubella, etc.
• Transfusion reaction
• Risk of incorrect cross - matching and transfusion
negative impact on immune system.
• .
Hazards of Blood Transfusion in USA
 Hemolytic reactions
1 in 40,000
 Non hemolytic febrile reactions 3-4%
 Anaphylactic reactions
1 in 20,000
 GVHD 0.1 to 1%
 TRALI 0.1-0.2%
 HBV
1 in 50,000
 HCV
1 in 3000
 HIV
1 in 1,50,000
Summary Protocol of Severe Anemia in Pregnancy
Pregnancy < 30 weeks
Iron deficiency
anemia
Folic acid
deficiency
Oral iron
therapy
Oral folate
therapy
Intolerance or noncompliance
Intramuscular
iron
Intravenous
iron
Summary Protocol of Severe Anemia in Pregnancy
Pregnancy 30-36 weeks
Iron
deficiency
Folic acid
deficiency
Parenteral
iron
Intramuscular
iron
Oral folate
therapy
Intravenous
iron
Pregnancy >36 weeks
Blood transfusion
Key Points of
Iron-deficiency Anemia
 IDA is an illness of low iron in the body.
 Iron makes Hb and healthy RBC which are needed for oxygenation
 Reasons of IDA: blood loss, either from disease or injury,





nutritional; defective absorption, ↑ demand such as during
pregnancy.
1 in 5 women of childbearing age and > 50% pregnant women have
iron-deficiency anemia.
Most common symptoms are fatigue & weakness.
Treated by stopping the bleeding, increasing iron in the diet, and
giving iron supplements.
Eating a well-balanced diet rich in iron and vitamins can prevent.
Can be successfully treated
CONCLUSION
 Proper antenatal care and awareness programmes for






prevention of anemia.
Adequate iron / folic acid prophylaxis in all antenatal
cases.
Early detection and timely referral to tertiary centers.
Management to be decided depending upon the cause of
anemia, type of anemia and severity of anemia.
Logical use of blood and blood components.
Proper intrapartum and postpartum care.
Motivation of the patient for acceptance of any
contraceptive method.
Mild and Moderate
 Nutrition
 Control of infestation
 Control of infection
 Iron and Folic acid supplement
 Economic reforms
 Education
 Cultural reforms
 Infrastructure development, etc.
Severe Anemia
 Management depends on the time at hand.
 If diagnosis:
 Preconception - oral, if not tolerated, parenteral
 First & second trimester - oral + parenteral
 Third trimester - parenteral + blood transfusion by PCV
 Late in third trimester and/ labor, blood transfusion by
PCV nasal O2, B T, digitalization and ICU
management with team approach.
 Clinical condition
 Associated risk factors
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