IN PREGNANCY

OUTLINE
 Introduction
 Definition and severity grading
 Effects of anemia in pregnancy
 Antenatal
 Intrapartum
 Post natal
 Classification of anemia
 Approach to diagnosis
 Discussion of each class - Diagnosis, management
 Management in Labor
INTRODUCTION
Most common nutritional disorder in the world
GLOBALLY: 528.7 million women of child bearing age affected
Most common medical disorder during pregnancy
GLOBAL PREVALENCE OF ANEMIA IN PREGNANCY: 38.2% (41.8 % in 2008)

WHO. The global anaemia prevalence, Geneva; 2015

STATISTICS
40% maternal deaths in 3rd world countries
25% direct maternal deaths

India contributes to 80% maternal deaths in South East Asia

Maternal Mortality in India 1997-2003, Registrar General of India

* 8-10 fold increase in maternal mortality if HB < 5 gm%

Brabin B. Trans R Soc Trop Med. 2003
 DEFINITION
-Statistical-
Condition of low circulating haemoglobin in which Hb concentration has fallen
below the threshold lying at two standard deviations below the median value for a
healthy matched population
-W.H.O. 2008-
Hb concentration < 11 g/dl and Hct < 33% in antenatal period and Hb < 10g/dl in
postpartum period

-United States Centers for disease control 1998-

The cut-off point suggested is 10.5 gm/dl in the second trimester and 11g/dl in
first and third trimester (5th percentile)
SEVERITY OF ANEMIA
HB (G%) ICMR 2009 WHO 2011
MILD 8.0-10.9 10-10.9
MODERATE 5-7.9 7.0-9.9
SEVERE <5 4.0-6.9
VERY SEVERE - <4
CLASSIFICATION OF ANEMIA
IN PREGNANCY
PHYSIOLOGICAL
ACQUIRED
• Nutritional anemia
Iron deficiency anemia
Megaloblastic anemia (vitamin B12 and folic acid deficiency)
• Anemia of chronic disease
• Anemia caused by blood loss
Acute (APH, PPH)
Chronic (hook worm infestation, bleeding piles etc.)
• Acquired hemolytic anemia
• Aplastic or hypo-plastic anemia

IRON DEFICIENCY ANEMIA – Most

common type
CLASSIFICATION OF ANEMIA
IN PREGNANCY
GENETIC
Haemoglobinopathies
• Thalassemias
• Sickle cell anemias
• Other haemoglobinopathies
Hereditary hemolytic anaemias
• RBC membrane defects-spherocytosis
• Red cell metabolism defects
Physiological anemia
of pregnancy CRITERIA:
Hb: 10 gm%, Hct: 30%
RBC: 3.2 million/mm3
P/S: Normocytic Normochromic
ADVANTAGES:
•Decreased blood viscosity:
reduced load on heart
•Facilitate blood flow through
placenta
•Protective buffer against blood
loss in 3rd stage
DISADVANTAGES:
•Increased circulatory burden on
diseased heart
•Fetus less efficiently oxygenated
MATERNAL CONSEQUENCES
ANTEPARTUM INTRAPARTUM
• Pre eclampsia (31 %) • Maternal exhaution/uterine inertia
• Intercurrent infection, sepsis • PPH
• Asymptomatic bacteremia/uria • Cardiac failure
• Cardiac failure • Shock
• Preterm labour
Mean BW was higher by 108g & POSTPARTUM
incidence of preterm delivery was • Puerperal sepsis
lower (8% vs 14%) in Fe
• Subinvolution
supplemented group
Siega-Riz ,et al .AJOG 2006 • Failing lactation
• APH (a/w folate deficiency) • Delayed wound healing
• PPROM (Hb < 5) • Puerperal venous thrombosis
• Pulmonary embolism
FETAL CONSEQUENCES
 IUGR/LBW (2 fold inc in LBW and perinatal mortality if Hb < 8)
Palma S, et al.J Epidem Comm Health. 2008
 Prematurity
 Still births (severe maternal anoxemia)
 Intra uterine deaths (anemia < 28 wks)
 Congenital malformations
 Increased risk of IDA early infancy (6 fold inc risk)
 Breast milk iron content significantly ↓ in severely anemic mothers
Kumar A et al.Pediatrics 2008
 ↑ in Neonatal deaths/Perinatal mortality
 Abnormal Social and Emotional behaviour, developmental delay
 IRON REQUIREMENTS DURING PREGNANCY
Maternal req. of total Iron -1000mg
150 mg saved d/t
 500 mg  Maternal Hb. Mass expansion amenorrhea
 300 mg  Fetus & Placenta !!!850 mg still needed!!!
 200mg  Shed through gut., urine & skin
Williams, 24th edition

 2.5 mg /day in early pregnancy

 4-6 mg /day from 20 -32 weeks Average 4 mg/ day
 6 – 8 mg/ day after 32 weeks

Lactation: 2.4 mg/day Stoltzfus et al. UNICEF 1998

Absorption of iron depends upon
 Amount of iron in the diet
 Bioavailability of iron
 Physiological requirements
Iron sources are two types
1) Haem iron (5%) : hemoglobin and myoglobin from red meat, poultry
and fish
Absorption is 15-30% ,can increase to 50% , not affected by inhibitors
2) Nonhaem iron (95%): fibers, green vegetables, jiggery, dried fruits;
Absorption is 10%, influenced by inhibitors and enhancers
IRON ABSORPTION
NORMAL IRON CYCLE
Duodenum Dietary iron
Utilization (average, 1 - 2 mg
Utilization
per day)

Plasma
transferrin (TIBC)
(3 mg)
Bone
Muscle marrow
(myoglobin) Circulating (300 mg)
(300 mg) erythrocytes
Storage
iron (hemoglobin)
(1,800 mg)
(Ferritin)
Sloughed mucosal cells
Desquamation/Menstruation
Other blood loss
(average, 1 - 2 mg per day) Reticuloendothelial
Liver
(1,000 mg) macrophages
Iron loss (600 mg)
Causes of IDA
Increase demand for iron particularly in 2nd & 3rd trimester
Low dietary intake
Malabsorption (Hypo-or achlorohydria/ inhibitors in food)
Grandmulti
Less birth spacing, pre pregnancy anemia
Early marriage, teenage pregnancies, multiple pregnancies
Hook worm infestation (0.03 ml blood loss by ankylostoma & 0.15 ml by Enterobius,
upto 5 mg iron loss/day in heavy infestation)
H/O menorrhagia: 20-30%
Higher risk with morning sickness
Aspirin/NSAIDS
Losses can increase with colorectal cancer, polyps
STAGES OF IRON DEFICIENCY ANEMIA

Harrison’s 19th edition

APPROACH TO DIAGNOSIS OF IDA
Obstetric – Recurrent pregnancy at
short intervals
Past
 Bleeding disorder;
 Koch’s, Malaria;
H/o blood transfusions
Chronic blood loss
Personal
 Dietary intake
 Food fadism
 Malabsorption, pica
GENERAL & SYSTEMIC
EXAMINATION
 Pallor –Conjunctiva, tongue, palate, nail, palm, vaginal mucosa

 Glossitis, stomatitis

 Koilonychia

 Dryness/roughness of skin, brittle hair

 Pulse - tachycardia, collapsing pulse

 Blood Pressure - Postural Hypotension

 CVS/Chest -tachycardia, tachypnoea , haemic murmur

 Pedal edema ,↑ JVP

 Look for septic focus
LABORATORY DIAGNOSIS

Complete Blood Count(CBC)

Peripheral Blood Film
HB HPLC (to rule out thalassemia)
Serum Iron Studies
Urine R/M, C/S
Liver/Kidney function tests
Stool for Ova/ cyst
USG whole abdomen
LABORATORY DIAGNOSIS
PERIPHERAL BLOOD FILM
•Microcytic, hypochromic
BONE MARROW EXAMINATION:
•Poikilocytosis, polychromasia, Pencil cells
Not routinely done
•Raised red cell distribution width
Indicated only when:
(Anisocytosis) •Failure of therapy
•No s/o hemolysis •Hypoplastic/aplastic anemia
•Kala azar
•Haemoparasites

BONE MARROW: Normoblastic

Reduction in stainable iron (GOLD STANDARD)
LABORATORY DIAGNOSIS
PARAMETER REFERENCE RANGE IDA
Hb 11-14 gm % ↓
RBC Count 4.0-5.2 million/cumm ↓
Physiological
MCV 82-98 fL ↓
Macrocytosis
MCH 27-33 pg ↓ (unreliable)
MCHC 31-35 % ↓
PCV 32-40 % ↓
Serum Iron 50-150 µg/dl ↓
APOFERRITIN + Ferrous iron:
TIBC 300-360 µg/dl ↑ FERRITIN (ferric form)
RDW < 14.5 % ↑ • Marker for storage iron
Serum Ferritin 15-150 µg/L ↓ • First to decrease
Transferrin Saturation 25-50 % ↓ • 1BEST
µg/L= 8 mg of storage iron
INDICATOR
Transferrin Receptor Protein 4-9 µg/L ↑ • APR:
Iron unreliable
deficiencyinat acute/chronic
cellular level
Red Cell Protoporphyrin <30 µg/dL ↑ • inflammation,
3-5 fold rise indelivery,
IDA liver disease,
Erythropoetin 15.20 U/L ↓ • malignancy,
Not affected hyperthyroidism,
by infection or heavy
Values riseintake
alcohol after 2-3 wks, >70 µg/dL
inflammation
Harrison’s 19th edition
sTfR- Ferritin ratio
 Indicates body iron stores
 Ratio increases from <100 (adeq
stores) to over 2000 during significant
iron depletion, median: 500

CHr- Reticulocyte Haemoglobin

Concentration
>28pg
Sensitive indicator that falls within days
of the onset of IDA
Mast AE,et al. Blood 99.2002
MANAGEMENT OF IRON DEFICIENCY ANAEMIA IN
PREGNANCY

AIM
To correct iron deficiency
To restore iron reserve
To correct associated complicating factor

CHOICE OF THERAPY
Depends on severity of anemia
Duration of pregnancy
Associated complicating factor
OPTIONS
• Simple
ORAL • Inexpensive
• Relatively non-toxic

• Expensive
PARENTERAL • Drug reactions
• Intolerance/non responsiveness to oral iron

• Severe anemia beyond 36 wks

• Replenish blood loss due to APH/ PPH
BLOOD • No response to oral / parenteral iron
TRANSFUSION • Sickle cell crises, Thal major
• Always PACKED RBC’s. Never whole blood
TREATMENT- DIETARY MEASURES

Consumption of iron rich food: jaggery, spinach, mustard leaves, sprouted pulses, red meat, fish,green
leafy veg, liver, eggs, peas, cereals (but contain phytic acid)

Cooking in iron utensils & Intake of heme iron

Food fortification: iron fortified salt, wheat, maize, milk
◦ Ferric orthophosphate (3.5 g per kg) and sodium acid sulphate (5 g per kg), - 1 mg of iron per gram of
salt
◦ Ferrous sulphate (3,500 ppm) and orthophosphoric acid or sodium orthophosphate (2,800 ppm),
bringing down the cost by nearly half
◦ Used in Midday meal programme NFHS 3 2005-06
SPATONE IRON PLUS: iron rich mineral water (0.20 mg/ml ferrous sulphate): available in UK
 DEWORMING IN PREGNANCY
Deworming once in pregnant patients in 2nd trimester in high endemic areas

If prevelance >50%, repeat in 3rd trimester as well

No adverse effects on
pregnancy outcome
Gyorkos TW. Pediatr Infect Dis J, 2006

- WHO 2005
RON SUPPLEMENTATION IN
REGNANCY
Developing countries
Ministry Of Health, Govt. Of India Recommendation:
(National Nutritional Anemia Control program) 1992

ALL ANC PATIENTS: 100 mg of elemental iron with 500 µg of folic acid in second
half of pregnancy for atleast 100 days.
THERAPEUTIC :200mg elemental iron /day + 1000 µg of folic acid + 3-6 months
post partum
IFA coverage - 65 % but only 23% of antenatal women found to have taken atleast 90 days of
IFA tablet
NFHS 3,2005-06
Implementation and scaling up of the IFA Supplementation
programme and management of all forms (mild, moderate and
severe) of IDA.

Ministry of Health & Family Welfare. 2013

SUPPLEMENTATION THROUGH THE LIFE
CYCLE
Age group Intervention/Dose Regime Service delivery
10–19 years 100 mg elemental iron & Weekly throughout the -School -through teachers
500 mcg FA period 10–19 years of -out-of-school-AWC
age and biannual Mobilization by ASHA
de-worming
Pregnant and 100 mg elemental iron & 1 tablet daily for 100 ANC/ ANM /ASHA
lactating 500 mcg FA days, starting after the Inclusion in MCP card
women first trimester, at
14–16 weeks of
gestation. To be
repeated for 100 days
post-partum.
Women in 100 mg elemental iron & Weekly throughout the Through ASHA
reproductive 500 mcg FA reproductive period during house visit for
age (WRA) group contraceptive distribution
Ministry of Health & Family Welfare. 2013
 WHO 2012

IF ANEMIA IS DIAGNOSED: 120 mg of elemental iron +

400 µg of folic acid till Hb rises to normal.
Thereafter, switch back to the standard dose
In countries where prevelance of anemia in pregnant
patients is < 20%

WHO 2012
DEVELOPED COUNTRIES
Benefit of iron supplementation in non –anemic pregnant
 Indications
women is unclear to supplement iron
• Multiparous
• Multiple pregnancy
No morbidity of supplementation
• Vegetarians
• Blood donors
• Low socio-economic status
Prevents anemia at delivery
• Immigrants esp from Middle & far east
(ACOG 2008)
(Nybo M, Ann Hematol. 2007)
 INTERMITTENT IRON
THERAPY

•Intermittent IFA: Feasible alternative to daily iron among those

pregnant women who are not anemic and have adequate antenatal care

•Similar maternal and infant outcomes at birth as daily supplementation

•Fewer side effects

Cochrane 2012
ORAL IRON THERAPY

 Start from 14-16 weeks

 Continue till 3-6 months postpartum
 Empty stomach / In between meals
 Start with low dose to minimize side effects (a/w dose of elemental iron)
 Iron solution: alternative but S/E staining of teeth
 Folate should be supplemented along with iron
 Avoid slow release/enteric coated forms
 Higher doses not effective
 FACTORS THAT MODIFY IRON
ABSORPTION
Heme>Fe2+
>Fe3+ Physical State
Vagotomy, H2 receptor blockers, calcium-based High Gastric pH
antacids decrease absorption
Crohn’s disease, Celiac disease Intestinal Structure
disruption
Phytates, tannins, tea, coffee, calcium, herbal drinks, Inhibitors
milk, multivitamins
Cobalt, Lead, Strontium Competitors
Ascorbate, Citrate, Amino acids, meat, iron deficiency, Facilitators
increased erythropoetic activity (bleeding, hemolysis,
high altitude)
COMMONLY USED IRON PREPARATIONS

Ferrous ascorbate Carbonyl iron Ferrous Bisglycinate

• Ascorbate prevents • Microparticles of • Amino acid chelate
oxidation of ferrous to purified elemental iron, • Absorption not
ferric iron not a salt decreased by phytates,
• Antioxidant effect • Low toxicity, lesser GI high bioavailability
protects GI mucosa s/e • Costly
• High bioavailabilty • Converted to HCl salt
• Most suitable for indian before abs
diet: more inhibitors • Absorption rate slow,
permits continued
release for 1-2 days

-IJMPS 2012
 COMMONLY USED IRON PREPARATIONS
FERROUS SULPHATE, FERROUS FUMARATE, FERROUS GLUCONATE
Cheapest
Most commonly used forms

FERRIC AMMONIUM CITRATE

Most commonly used ferric salt
Requires conversion to ferrous salt in stomach, less bioavailability

FERRIC HYDROXIDE POLYMALTOSE COMPLEX

GI irritation less, costly
Generally poor bioavailabilty
Hb failed to rise, women remained iron deficient at the time of delivery
Also, new borns exposed to risk of IUGR
Mehta BC. Ind J Med Sci 2001
 IRON PREPARATIONS Elemental Cost
PREPARATION Brands Total iron iron % Elemental
(30tab)
(mg/tab) Iron
(mg/tab) Rs
Ferrous sulphate Fefol 200 65 32 % 100
Ferrous fumarate Autrin, Livogen 300 100,50 33 % 60-70
/150
Ferrous Gluconate MC Tone, 300 36, 12 % 320
Livogen Hemtonic 15mg/5ml

Ferrous ascorbate OroferXT, RB Tone 730 100 14 % 180-220

Forte, Mashyne,
Ferikind, Ferris

Carbonyl Iron FeoSol 100 98 98 % 160

Ferrous-Bisglycinate Globac-XT 60 20 % 280

Ferric amm citrate Dexorange 160 30 18 % 68
 SIDE EFFECTS
Constipation

Bloating , Diarrhoea, Abdominal cramps

Heartburn, Nausea

Dark stools

Oxidative radical injury

Drug interactions:
◦ ↓ absorption and efficacy of levothyroxine, methyldopa, antibiotics - insoluble complexes in
GIT
◦ Antacids ,H2 receptor blockers, PPI, antibiotics, calcium supplements - ↓ iron absorption
COMPARISON OF EFFICACY, TOLERABILITY
AND COST OF NEWER WITH CONVENTIONAL
ORAL IRON PREPARATION
Pregnant women between 12 to 22 weeks with Hb < 10 gm/dl
Group A (n= 20) Group B (n=20) Group C (n= 20)
Ferrous fumarate 100 mg OD Ferrous bisglycinate 100 mg OD Carbonyl iron 100 mg 0D

Rise in Hb and MCV- No significant difference

GROUP A: - Max side effects

- Cheapest
- Highest rise in ferritin
-S.S. Patil. Al Ameen J Med Sci, 2013
ORAL IRON THERAPY- CAUSES OF FAILURE
RATE OF IMPROVEMENT:
Hb rises after 2 wks - ↑ 0.8 g/dl/week
Reticulocytosis within 7-10 days
CAUSES OF FAILURE OF ORAL THERAPY (No response in 2 wks)
 Poor patient compliance - side effects
 Malabsorption syndrome
 Presence of chronic infection
 Continuous loss of iron
 Concomitant folate deficiency
 Incorrect Dx - aplastic anemia, MDS
 PARENTERAL IRON THERAPY
INDICATIONS CONTRA-INDICATIONS
Intolerance to oral iron Anemia not attributable to iron deficiency
Mal absorption Iron overload
Poor compliance Hypersensitivity to I/V iron
Routine supplementation to TPN Liver Cirrhosis
Patients on erythropoietin
Acute or chronic infection
No response to oral iron in 2 weeks(Hb
rise/ retic count) First trimester of pregnancy
IDA in third trimester Acute renal failure
H/o severe asthma, eczema or other
atopic allergies
( NHS 2008)
 PARENTERAL THERAPY- PREREQUISITES

 Correct diagnosis of IDA.(R/o Thalassemia)

 Adequate supervision in hospital setting
 Facility for management of anaphylaxis
 Stop Oral Iron atleast 24 hrs prior to therapy to avoid toxic reaction.
 Look for reaction – chest pain, rigor chills, hypotension, dyspnoea,
haemolysis & anaphylactic reaction
 Sensitivity test - 1ml test dose prior to infusion

Not required for iron sucrose & Ferric carboxymaltose

PARENTERAL IRON PREPARATIONS
TYPE I TYPE II TYPE III
Iron dextran Iron sucrose Iron gluconate
Iron carboxymaltose

-Molecular weight Molecular weight Molecular weight

(>1,00,000 d), (30,000- 1,00,000 d) (<50,000 d)
- high stability Medium stability Unstable
Robust and strong Semi- robust and moderately Labile and weak
strong
Can be given in high doses Non transferrin bound labile Free iron causes tissue
iron causes adverse events if toxicity
given in high doses
DOSE CALCULATION

Elemental iron needed (mg)

[Target Hb(15 g%) – patient’s Hb (g/l)] x weight (kg) x 2.3 + (500-1000 for
stores)
Harrison’s Principles of Internal Medicine, 19th edition

Simple method
250 x Hb Deficit + 50% for stores
 IRON DEXTRAN

•5% iron and 20% dextran

•It contains 50 mg/mL of elemental iron, most of which is present in the ferric state.
Inbolus
•Can be given i.m, i.v view or i.vof poor
infusion compliance it has been
recommended
•Test dose required (0.5 ml) in our country to administer
•Prolonged use:Staining of the skin, formation of sterile abscesses, tissue necrosis or atrophy, and sarcoma
formation
“2 doses of inj. Iron dextran (250 mg
each) at 4 weekly interval along withBr Med J 1973
-A.E. Mackinnon.

tetanus toxoid injection”

Adverse reactions: fever, malaise, arthralgia, hypotension, urticaria
Anaphylactic reactions: 0.1- 0.6- percent
Bhatt RV. J Obstet Gynecol India, 1997
- JAMA 1980

Z- track technique- minimises skin staining

Z Track Technique to administer IM IRON PREPARATION
ORAL IRON vs IRON DEXTRAN
STUDY DESIGN: RCTProspective RCT
GROUP 1 (n= 100) GROUP 2 (n= 100)

100 mg oral iron daily 250 mg of i.m iron dextran monthly 3 doses

RESULTS: Hb improved significantly in both the groups

Serum ferritin improved significantly in i.m group

Systemic side effects more in i.m group and gastro intestinal side effects more in oral
group
- Jai. B. Sharma. Am J Clin Nutr, 2004
IRON SUCROSE

200-300mg biweekly, I/V infusion

Maximum- 600mg/wk
Can be given undiluted slowly @ 1ml/ min or infusion of 200 mg/200 ml
NS (unstable in dextrose) over 15 mins
Higher dose(>300mg/dose or 600mg/wk): Release of free iron from less
tightly bound carbohydrate complexes- infusion reactions
pH: alkaline(>10), cant be given i.m  muscle damage
Disadvantages: Multiple visits & dose limitations
Life threatening fatal reactions- 0.002%
 Iron dextran Iron Sucrose
Conc 50 mg / ml 20 mg/ml

Test dose Required ± (Physician discretion)

Dosage 100 mg over 2-5 mins. 100 mg over 5 mins.

IM/IV infusion IV inj.
(dil in .9% NS)

Maintanance dose Daily until calculated dose of iron 2-3 times a week
is reached
Diluent 0.9% sodium chloride 0.9 % sodium chloride

Total dose infusion Yes No

Bio availability + ++

Clearance 10 – 20 mg/hr Unknown

Safety profile C B
IRON SUCROSE vs ORAL IRON IN PREGNANCY AND
POSTPARTUM
Study design: RCT
271 anemic women (148 pregnant women and 123 post partum women) , Hb < 11 gm/dl

GROUP 1 GROUP 2
Oral Ferrous sulphate (2 tabs OD) I V Iron sucrose (400 mg)

RESULTS:
Ferritin was significantly higher in group 2 compared to the oral iron treatment group
(p = 0.004)
Hb values did not differ between the groups.
No serious adverse drug reactions were observed
- Froessler B. J Matern Fetal Neonatal Med 2013
AIIMS
experience

Prospective clinical trial

100 Pregnant women with Hb 5-9g%
Exclusion- thalassemia, renal disease ,multiple pregnancy, sickle
cell disease
Intravenous ISC - 200 mg twice weekly.
Mean dose – 1777± 168mg ; duration- 4.5± 1.0 weeks
 RESULTS

Parameters Baseline 8 weeks

Mean Hb (g%) 7.62±0.612 11.20±0.73

Serum iron( µg/dL) 33.54±5.784 92.42±19.6
S. ferritin(µg/L) 10.09±3.5 69±23.1
 I/V ISC increases Hb & iron stores faster than oral iron
 Can replace intramuscular iron preparations
 Further long term studies are required to recommend its use at
peripheral level.

Kriplani et al. IJMR 2013

Need of effective and safe
iron preparation to
decrease the cost of
multiple visits
 Newer I/V iron preparations
Ferric carboxymaltose (Orofer FCM)
◦ No dextran
◦ 15mg/kg, upto 1000mg single dose
◦ Neutral pH and physiological osmolarity
Test dose not
Ferumoxytol (Feraheme)
◦ Partial dextran content required
◦ Anaphylaxis reported
Iron isomaltoside
◦ 20mg/kg infusion can be given within 1hr
◦ Available only in Europe
David Gozzard.Drug Design, Development and Therapy 2011
FERRIC CARBOXYMALTOSE

Non-dextran containing Fe complex DOSAGE

Boluses
Approved for treatment of anemia by • Maximum- 1000mg per dose

DCG(I) in February 2011 • <66kg- 15mg/kg/dose

• 100 mg /minute IV for up to 500 mg. Thereafter
FDA approved in August 2013
500mg for 15 min.
 Iron deficient anemia
 Non dialysis dependent chronic kidney disease
Infusion
 Not approved in India in pregnancy • 1000mg in 250ml saline – over 15 min
Don’t give >1000mg /sitting: can
lead to hemochromatosis
Max dose not to exceed
 FCM in pregnancy (Category C)
No adequate well- controlled trials

1st trimester- contraindicated

2nd/ 3rd trimester- careful risk/ benefit evaluation

No long term studies to evaluate the effect on fetus

First PROSPECTIVE STUDY for FCM use in pregnancy done in 2014
65 anemic patients (Hb < 11.5 gm%) given Inj FCM 15 mg/kg btw 24-40 wks
FCM in pregnancy :
FCM vs ISC for anemia in pregnancy
Retrospective analysis (Switzerland)
Pregnant women(14-34 wk)
Gp I(n-103)- FCM (1000mg/ week)
Gp II(n-103)- ISC (200mg biweekly)

ParametersFCM- safe
FCM in 2nd & 3ISC
rd
trimester
Hb-(before
Can Rx) replace
9.8 ISC once safety
9.5 confirmed
Hb(after in
Rx) randomized
11.3 prospective
11.0 trials
Adverse events Less(8) More (11)

Christoph P. J Perinat Med 2012

INCLUSION CRITERIA: Post partum women with Hb < 10 gm%

GROUP 1(n=100) • Oral Iron (100 mg ferrous ascorbate OD)

GROUP 2(n=100) • IV Iron Sucrose

GROUP 3(n=100) • IV FCM

Rathod S. Int J App Basic Med Res 2015;5:25-30

 Mean Hb Rise Mean Ferritin Rise
14 400
12 350

10 300

8
FCM – safe, effective
Oral iron and well250tolerated alternative to
200 Oral Iron
6
oral iron for treatment of post partum anemia Iron Sucrose
Iron Sucrose
FCM
4 150 FCM
Patient friendly approach
2 100

0 50
Baseline Hb 2 Hb 6
Hb wks wks 0
Baseline Ferritin 2 Ferritin 6
Ferritin wks wks

Rathod S. Int J App Basic Med Res 2015;5:25-30

Management of anemic patients in labour
• First Stage
Propped up position
Adequate analgesia
Antibiotic prophylaxis
W/F signs of pulmonary edema
Uterine inertia & maternal exhaustion
Arrangement for oxygen and blood
Digitalization may be required in cardiac failure due to severe
anemia
Management of anemic patients in labour
•Second stage– Cut short by forceps application
Active management of third stage

•During puerperium
Adequate rest
Iron and folate therapy for 3 months
Infection ,if any should be treated energetically
Careful watch for puerperal sepsis, failing lactation; sub
involution of uterus and thromboembolism
MEGALOBLASTIC ANAEMIA
Incidence – 0.2 – 5 %
Caused by folic acid deficiency (more common) & Vit B12 deficiency
Causes
•Decreased Intake –alcoholism, diet
•Impaired absorption- Pregnancy causes 20-30
 Malabsorption, gastrectomy , ileitis, ileal resection
fold increase in folate
 Addisonian pernicious anaemia.
 Diffuse intestinal diseases
requirement
 Parasitic infections (150-450 µg / day)
 Anticonvulsants, OCP s
•↑ Requirement- hyperthyroidism, cancer, hemolytic states.
•Impaired utilisation- drugs
•↑Loss - hemodialysis
MEGALOBLASTIC ANAEMIA
Folic acid reduced to DHFA then THFA, used in nucleic acid synthesis, is
required for cell growth & division
So active tissue reproduction & growth more dependant on supply of folic acid
Coexists with IDA
Effects of folate deficiency (d/t raised Homocysteine levels)
o Abortion
o Fetal malformation, NTD
o Prematurity, IUGR
o Pre eclampsia, Abruption
CLINICAL FEATURES
•Insidious onset, mostly in last trimester
•Anemia not responding to iron therapy
•Anorexia, occasional vomiting and diarrhea
•Pallor of varying degree
•Ulceration in mouth and tongue
•Glossitis
•Enlarged liver and spleen
•Hemorrhagic patches under the skin and conjunctiva
•Peripheral neuropathy
Vit B12 Deficiency
•Subacute combined degeneration of the Spinal cord
DIAGNOSIS
Serum B 12 pg/ml Serum folate ng/ml Erythrocyte folate
ng/ml
Normal 200-900 5-16 >150
Vit B12 def <100 ↓ >16↑ or normal <150↓
Folate def 200-900 <3↓ <150 ↓

a) MCV > 100 fl, MCH > 33pg, but MCHC is Normal
b) P/S: Hypersegmentation of neutrophils in >4% neutrophils (earliest feature)
c) Howell-Jolly bodies
d) Low retic count, pancytopenia
e) Serum Fe is Normal or high, TIBC is low, elevated LDH, homocysteine levels
f) UGIE, LGIE
g) Serum methyl malonic acid – highly sensitive & specific, detects early functional vit B12 def
h) Schilling Test: not done in pregnancy
Treatment –Supplementation
Folate def
 Rule out Vit B12 deficit, neurological deficits cannot be corrected with FA alone
 Prophylactic: 400 µg/day orally in pregnancy, 600µg/day in lactation WHO,2012
 Therapeutic: 4 mg/day till 4 wks post partum , treat IDA as well
 In the presence of haemoglobinopathies, hemolytic conditions: 5-10 mg/day
 RESPONSE: Increase retic count in 6-8 days, decrease in LDH in 3-4 days, P/S normalizes in
5 wks

Vitamin - B12 def

 Recommended daily intake: 2.6 µg/day
 Parenteral - Inj Hydroxycobalamin 1000 mcg three times a week X 2 weeks, then 3
monthly (ACOG)
 Alternatively, Inj Hydroxycobalamin 1000 µg weekly x 8 wks, then 3 monthly for life (CDC)
 MANAGEMENT OF SEVERE ANEMIA IN PREGNANCY
Pregnancy < 30 weeks Pregnancy 30 -36 weeks Pregnancy > 36 weeks

Iron deficiency Folic acid deficiency Iron deficiency Folic acid deficiency
Blood transfusion
anaemia anaemia

Oral iron therapy Oral folate Parenteral Iron Oral Folate therapy
therapy

Intolerance or Intramuscular iron Intravenous

non-compliance iron

Intramuscular iron Intravenous

iron Dr J.B.Sharma, JIMSA, 2010
HAEMOGLOBINOPATHIES
<3 % anemias detected in pregnancy
Sickle cell disease
 Sickle cell anaemia (most severe)
 Sickle cell trait
 Sickle cell beta thalassemia,
 Haemoglobin SC disease
Thalassemia
- Alpha thalassaemia.
- Beta thalassaemia: -Major
-Minor
-Intermediate
SICKLE CELL ANAEMIA
Valine substituted for glutamic acid at 6th position on β chain of Hb molecule
Common variants -SS ( sickle cell anemia)
-SA ( sickle cell trait)
Hb S is poorly soluble in low oxygen tension situations, cause sickling
Decreased life spanMost common
from 120 days to 20inherited
days
hematological disease
Hb SS worldwide Hb SA
Cell trait Homozygous Heterozygous
HbS 70 – 90%, rest HbF 10 – 40%, 40-60% HbA
Hb (g/dl) 6-9 13 -15
Life expectancy 30 yrs less than avg normal
Propensity for sickling ++++ + (O2 falls < 40%)
 SIGNS & SYMPTOMS
Complications related to hemolysis RISKS TO
 Anemia (Hct 15 – 30%)
 Cholelithiasis THE FETUS:
 Acute aplastic episodes •Abortion
•IUGR
•Preterm birth
Infectious complications (d/t hyposplenism) •Severe oligo
 Streptococcus pneumonia and Hemophilus
influenzae
 UTI: E.coli
 Osteomyelitis
Sonwane Anju, et al. J Obstet Gynecol India.2005
 SIGNS & SYMPTOMS
Vaso-occlusive complications
• Painful episodes-most common(50%): exacerbated by cold, infection, exercise
and stress
• Acute chest syndrome(20%)
• Spontaneous abortion
• Hypertensive disorders of pregnancy
• Thromboembolic complications, strokes
• Renal insufficiency
• Splenic sequestration
• Proliferative retinopathy
• Bone pains, leg ulcers, osteonecrosis
DIAGNOSIS
• Hb solubility test- cheap, rapid and simple but cant differentiate
btw homozygous and trait
• Sickling test, Hb electrophoresis
• P/S: -sickle cells
-howell jolly bodies
-target cells
-persistant reticulocytosis (10-20%)
• CBC, LFT, KFT, retic count, ferritin and folate levels
• Red cell antibody screening (risk of hemolysis in fetus)
 MANAGEMENT
 Multidisciplinary approach
 Partner screening, option of prenatal diagnosis
 Review prev h/o crises and its management, drug history
 Folic acid-5 mg OD preconceptionally and throughout the pregnancy, iron not needed
unless iron deficiency is documented
 If taking Hydroxurea, should be stopped 3 months prior conception
 ACE inhibitors & angiotensin receptor blockers stopped before conception
 Pneumococcal, Hib and meningococcal vaccination preconceptionally

 Antenatal visit every 2-3 wks, assess symptoms

 USG for GP/Liq from 24 wks, repeated 4 wkly, earlier if IUGR present
Management of sickle cell Disease in pregnancy. RCOG2011
 MANAGEMENT
 Routine BP measurement and urinalysis to detect HTN and proteinuria/UTI
 Retinal screening/fundoscopy for PR, screening for iron overload(serum ferritin)
 Screening for PAH by echo
 Antibiotic prophylaxis-Penicillin 250 mg BD/erythromycin, analgesia with NSAIDs/
opiods
 Start low dose aspirin: 75 mg OD from 12 wks
 Thromboprophylaxis with LMWH only if other risk factors present, to be given if
admitted antenatally
 Blood transfusion indicated only for acute anemia, sickling crises, twins,
preclampsia, ACS : exchange transfusion beneficial
Management of sickle cell Disease in pregnancy. RCOG2011
LABOR AND DELIVERY:
 Deliver at 38 wks
 Keep warm, hydrated and oxygenated
 Adequate analgesia (epidural preferred)
 Continuous CTG
 Blood transfusion if Hb < 8 gm/dl
 Thromboprophylaxis with LMWH
or heparin in case of crises
 Caesarean for obstetric indication only
 Alert paediatrician: opioid
dependance in newborn, send cord
blood for haemoglobinopathy testing
POST PARTUM:
 Adequate hydration and
oxygenation
 Low threshold for antibiotics
 Prophylactic subcutaneous LMWH for
7 days after vaginal delivery & 6 weeks
following a caesarean section
 Offer contraception: barrier
method(preferred), POP, injectables,
sterilization ; IUD’s, OCP’s :relative
contraindication
Thalassemia
Quantitative disorder
α-thalassemia - deletion from chromosome 16 of α globulin chains
◦ α-thalassemia major : Hb Bart (γ4): incompatible with life, intrauterine hydrops
◦ Hemoglobin H dis – (β4 chains formed) mod anaemia with reticulocytosis
◦ α-thalassemia trait - mild hypochromic microcytic anaemia of exclusion
◦ Silent α-thalassemia carrier
β-thalassemia - point mutations /partial deletions of chromosome 11, over 100 mutations
identified
β-thalassemia Major (cooley’s anaemia)-
• appears by 3-6 months of age
• Hepatosplenomegaly, iron overload
• Severely impaired fertility, hypogonadotropic hypogonadism
β-thalassemia Minor-fertility not impaired
 Diff btw IDA and Thalassemia
Tests Iron deficiency anemia Thalassemia
Peripheral smear Micro/hypo Micro/hypo with targeting

Serum Iron (µg/L) < 30 Normal to high

TIBC >360 Normal

Percent saturaion < 10 30-80

Mentzer’s Index:< 15
Ferritin (µg/L) 50-300
MCV/RBC count x 100
Hb pattern on Normal Abnormal with Beta Thal, can
electrophoresis be normal with alpha thal

NESTROFT Test Positive Positive

Mentzer’s index > 13 < 13

 Management of β-thalassemia major
Genetic counselling - partner Hb electrophoresis
Optimize iron chelation preconceptionally,stop desferroxamine when planning pregnancy
Blood group antibodies
Viral screen
Ferritin monitoring - every month to achieve level 1000-2000mcg/L
Baseline cardiac status - Echo, ECG, MRI for cardiac siderosis
Spontaneous miscarriage & fetal loss- 9%-33%
Multiple pregnancy, preterm birth- increased
Obstt complications- Gest HTN & pre-eclampsia (most frequent; 2.5%- 20%), GDM (10-
20%), placental abruption(3.8%-6.7%), UTI(3.8%)
Hypothyroidism – 9%
Raffaella Origa,et al.Haematologica.2010
•Folic acid 5 mg/day
•Supplement calcium and Vit D, stop bisphophonates
•Cardiac function monitored at 12 weeks, transfusion, delivery , puerperium
•Blood transfusion Hb>10g/dl
•Fetal surveillance from 34 weeeks to detect IUGR(17%)
Raffaella Origa,et al.Haematologica.2010

Labour management
Induction of labour –no hematological indication
Mode of delivery-high LSCS rate: short maternal stature, fetal distress – placental
deposition of iron, uncertain future fertility
Haemolytic anemia
Accelerated red cell destruction
CLINICAL FEATURES: Anemia, jaundice, splenomegaly, pigmane gall stones

INTRINSIC Serum unconjugated

bilirubin
Increased
•Haemoglobinopathy
Serum LDH (and Increased
•Red cell membrane LDH1:LDH2)
defect Serum haptoglobin Decreased
•Red cell enzyme defect Urine hemoglobin Present
Urine hemosiderin Present
Urine urobilinogen Increased
EXTRINSIC Cr51-RBC lifespan Decreased
•Autoimmune Reticulocyte count Increased
•Haemolytic anemia
•DIC
•TTP
HEMOLYTIC ANAEMIA
INTRINSIC
Hereditary spherocytosis
1:2000 North European descent
Autosomal dominant
Hb: 6-8 gm% in 10 % patient
Diagnosis- ↑osmotic fragility, spherocytes in peripheral smear, flow cytometry
↑ fetal loss in first trimester, anaemia, splenomegaly, jaundice,gall stones
Aplastic crisis (parvovirus induced)
Splenectomy: vaccination and prophylactic Penicillin V
Pyruvate kinase deficiency
AR
Non spherocytic hemolytic anemia, can worsen in pregnancy
PK def in fetus - non immune hydrops fetalis
G6 PD deficiency
X- linked recessive, women heterozygous
West african , mediterranean, or middle east
Non spherocytic hemolytic anemia, Heinz bodies
Avoid vit-C, nitrofurantoin, chloroquine, vitamin K
Folic acid supplementation must
Drug induced hemolysis - self limited, aggressive hydration
 WARM AIHA COLD AIHA
Autoimmune
•Abrupt onset hemolytic•Insidious
anemia onset
•IgG, 37˚ C •IgM, complement,
MOST•CAUSES:SLE,
COMMON CLL,ACQUIRED
RA, •4-30˚C
HEMOLYTIC ANEMIA
Lymphoma, drugs(methyl- •CAUSES: Mycoplasma,
DCTdopa, mefenamic
positive with acid, mainstay
spherocytes:
cimetidine, cefazolin)
lymphoma,
of rarely IM
diagnosis
•Ab does not cross
•Ab may cross placenta and placenta: fetus not affected
TRIAD: -Abrupt
affect fetusonset
-Jaundice
-Splenomegaly
Autoimmune Hemolytic Anemia
Primary
Secondary (drugs, infection, autoimmune disease, neoplasia)

TREATMENT:
Treat underlying disease
Glucocorticoids (Prednisone: 1mg/kg/day)
2nd line: Immunosuppressants (Rituximab, cyclophosphamide,
azathioprine, cyclosporine)
Splenectomy
Transfusion if no response to treatment (difficult cross matching)
 Other immune hemolytic anemia
Alloantibody hemolytic anemia
Transfusion reaction
Feto-maternal incompatibility (Kleihauer-Betke test)

Drug related Hemolytic anemia

Toxic immune complex (drug+Ab+C3)
- Quinine, Quinidine, Rifampin, INH, Sulfonamides,
Tetracyclin
Hapten formation (anti-IgG)
- PCN, methicillin, ampicillin
Anemia of Chronic Disease(ACD)
Causes
◦Parasitic & bacterial disease
◦Chronic viral infections-HIV
◦Chronic inflammatory disease
◦Chronic renal disease
Nemeth E . J Clin Invest 113, 2004
Mechanism-
◦↑ circulating hepcidin levels which blocks Fe
release from enterocytes and RE system, even with
 Click icon to add picture

Pathophysiology
Anemia of Chronic Disease
Management-
•Treat Cause
•Treat UTI/ ATT for TB/ Erythropoeitin therapy in renal disease/
deworming
•Treat IDA if present: can be diagnosed in ACD by elevated TfR and
/or ZnPP
Hastka J,et al . Clin Chem 38, 1992.
Skikne BS,et al. Blood 75.1990.
Renal Anaemia
Renal failure
Renal transplanted patients
Mechanism
• Erythropoietin def-primary cause
• Chronic inflammation
• Iron deficiency along with folic acid and carnitine deficiency
• Decreased half life of erythrocytes-uraemia
Treatment –Recomb erythropoietin when Hct < 20%
Ramin et al 2006
 ERYTHROPOIETIN IN PREGNANCY
 Human EPO gene-chr 7
 Mol wt-34,000
 T1/2: 2-4 hr
 Most important stimuli- hypoxia & anaemia
 2-4 times ↑ in pregancy
The most common side effect - aggravation of hypertension in 20% to 30% of
patients associated with too rapid ↑ in hematocrit
Dose
◦ 50-150 U/kg s.c, every 2-3 days
◦ Decrease by 25 U/kg every 4 wks: lowest possible maintainance dose
◦ Supplement iron and folic acid
 INDICATIONS
Chronic renal failure
AIDS
Rheumatoid arthritis
Malignancy
Sickle cell disease
Erythropoetin may be considered in patients requiring rapid correction of
anemia or in patients who do not respond to intravenous iron therapy alone
Breymann c,.et al. Ajog, 2001
APLASTIC ANAEMIA
Pancytopenia and bone marrow hypocellularity
MMR 15 - 50%
Hereditry- Fanconi’s anaemia
Acquired
 Radiation
 Viruses- parvovirus, hepatitis (non-a, non-b),EBV
 Drugs- marrow suppressive chemotheraputic agents -alkylating agents;
antimetabolites,chloramphenicol, quinacrine, phenylbutazone; gold, hydantoin
 Chemicals/toxins- benzene, weed killers/insecticides, arsenic, glue sniffing
 Immune disorders- SLE
 Management of aplastic anaemia
DIAGNOSIS: Bone marrow aspiration with cytogenetic analysis and chromosome fragility tests
Pregnancy may exacerbate bone marrow depression
1st Trimester: Terminate pregnancy, else supportive treatment
Late pregnancy/refusing termination: First line of therapy - erythropoietin and GM-CSF
If this fails: thymocyte gamma globulin , high-dose steroids & cyclosporine.
• Maintain Hb by transfusion
• Prevent & treat infections
• Splenectomy
• Delivery: preferably by vaginal route
• BMT after delivery(if no spont recovery)-BMT ↑ survival rate by 50-80%
 PNH
Rare hemolytic disorder - abnormality in RBC membrane that makes susceptible to
complement mediated intravascular hemolysis
Diagnosis: Hematuria, Hams test, sucrose lysis test, co-existent iron deficiency
Complications –Thrombotic events, Budd chiari syndrome (m.c cause of death)
Fertility is low.
 Prophylactic washed RBC transfusions
Folic acid supplementation
Steroids to ↓hemolysis in acute episode
BMT, androgens – no role in pregnancy
Postpartum thrombotic events are common & complete anticoagulation with
warfarin is needed
 TAKE HOME MESSAGE
Anemia is a major global health concern
Contributes significantly to maternal morbidity and mortality
Iron fortification of food items combined with iron supplements has proven to
be efficient
Oral iron supplementation is strongly recommended in all pregnant women
especially in developing countries
Parenteral iron provides quick and better correction and also builds up iron
stores but vigilance is must
e efforts should be dedicated to tackle this massive problem--we have the
, and we know the ways: implementation needed
THANK YOU