ANEMIA IN PREGNANCY - IDA: CHANGING CONCEPT

Dr Veena AgrawalM.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 AgrawalDGO

Consultant Agrawal Hospital & Research CentreGwalior, M.P. India

Anemia is a sign, not a disease of dynamic process

World Health Organization 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:NutritionalIron deficiency anemia (60%),Macrocytic anemia (10%) due to def of folic acid

and/or vitamin B12Dimorphic and protein deficiency anemia (30%) in

extreme malnutrition

Causes of AnemiaHemorrhagic

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 AnemiaHb: 10gm%RBC: 3.2 million/mm3PCV: 30%Peripheral smear showing normal morphology of

RBC with central pallor

Significance of Hypervolemia1. 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.

IDA12th 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 ICMRMild 10-11mg% Moderate 7-10.9mg%Severe 4 - 6.9mg% Very severe <4mg%

Normal Irondepletion

Irondeficient

erythropoiesis

Irondeficiency

anemiaStorage iron

Transport iron

Erythorin iron

Marrow iron

Plasma ferritin (µg/l)

Transferrin saturation(%)

Iron absorption

2-3+ 0 trace 0 0

100±60 < 20 10 <10

35±15 Normal Normal Microcytic hypochromic

Normal ± + +

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 %

Normal Levels

Requirement of IronIRON 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

Amountmg

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 RequirementsIron requirement for normal pregnancy is 1gm

200 mg is excreted300 mg is transferred to fetus500 mg is need for mother

Total volume of RBC inc is 450 ml1 ml of RBCs contains 1.1 mg of iron450 ml X 1.1 mg/ml = 500 mg

Daily average is 6-7 mg/day

Early Pregnancy

20 – 32 weeks

32 – 40 weeks

2.5 mg. / day 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

Decreased absorption

Increased blood loss

Poor diet

Increased requirements

Causes of IDA

Anemia: Etiologies Inadequate dietary intake

Poor nutrition Chronic alcoholism Decreased consumption of

animal protein and ascorbic acid  

Increased iron demands Multiparity Diarrhea, HIV/ AIDS and UTI Recurrent Infections-

Tuberculosis, Amoebiasis , Giardiasis, Roundworm

other infectious diseases

 Inadequate GIT absorption Malabsorption syndromes Certain drugs/foods  

Blood loss Hookworm infestation Malaria Bleeding piles &gums Surgery Gastrointestinal bleeding Trauma Dialysis

 

Low Iron Intake or Low Iron AbsorptionHaemolysis due to malariaworm 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 PCVBrain damageNecrotising enterocolitisHypoglycemiaHypocalcemiaHyperbilirubinimiaRDS

At Birth Hb – 18 to 20 gms %, PCV – 55 to 60 %

Severe Anemia

Fetal hypoxia

Prolonged period

Neurological deficit

Short duration

IQ less, slow

learner

Fetal hypoxia leads to an increase in the cord blood EPO.

Cord blood EPO correlates with perinatal brain damage.

Release of placental stress hormones (CRH,Nor epinephrine)

Fetal release of ACTH and cortisol

Abnormal trophoblast invasion and release of hypoxic inducible factor

Early anaemia during gestation

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, intra- partum & 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 CAREAs a routine - No differenceRegistration

Counseling

Regular check up weight, B.P., Hb%, urine

Prevention of complications

Immunizations

Care in addition to routine ANCH & P of AnemiaInvestigate for

Grade of anemiaType Severity of IDAcause

Tx of anemiaTx the cause of anemia ie. deworming, Antimalarial

Intrapartum Managementif patient comes in labor

Individuals who MUST present in labor roomSkilled Birth attendant's AnesthesiologistPediatricianNursing 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 patentBl arranged - PCVMonitor pt for sign of CCF esp. immediately

postpartumEarly cord clampingNo metherginCut shirt 2nd stage laborIV Diuretic Antibiotics

Postpartum ManagementMonitor patient for sign of CCFAntibiotics Otherwise same

Clinical Feature of Anemia

Symptoms:Mild anemia; usually asymptomaticModerate 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 AnemiaSigns:PallorNail changes – KoilonychiaAngular cheilosis, Glossitis, StomatitisOedemaHyperdynamic 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 & HaematocritPeripheral 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 storesTransferrin 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 Lab Testing for Iron Deficiency Anemia (IDA)Iron Deficiency Anemia (IDA)

Patient with anemia,

Ferritin > 100

Ferritin 20-100

Ferritin < 20,or Iron < 50and IBC > 450

Ferritin > 20,or Iron > 50and IBC < 450

sTR<45

sTR>45

IDA Workup for other causes of anemia

Iron therapy

Look for source of blood loss

Check ferritin, Iron, IBC level

Prevention

Dietary modificationIron supplementation of adolescent & non pregnant

femaleTx of Hookworm infestationControl of malariaIron supplementation in pregnant WomenFood fortification Antenatal care for early recognitionOptimal 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.

DietLow Bioavailability Rice, Wheat

Maize

Potato

High Bioavailability Eggs

Fish

Meat

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 g 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 improvementlaboratory indices

Reticulocyte countHemoglobinFerritin levelsTASTNewer 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 IronTherapeutic 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 compliance2. Concomitant folate deficiency3. Continuous loss of blood through hookworm infestation or bleeding hemorrhoids4. Co-existing infection5. Faulty iron absorption6. Inaccurate diagnosis

Non iron deficiency microcytic anemiaa. Thalassaemia

b. Pyridoxine deficiencyc. Lead poisoningd. Sideroblastic anemiae. 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 TherapyIndicated:

when unable to take iron due to side effects Non compliantSuffers from inflammatory bowel diseaseNear termWith chronic renal diseasePostpartum, especially in those who have had significant blood loss at deliveryPre – 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)

.

PostpartumHigh 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 diseasePts with ferritin > 800 ng/mL or transferrin saturation

> 50%.

Disadvantages

PainNausea vomiting, headache Skin discolorationAbscess formationFeverLymphadenopathyAllergic reactionAnaphylaxis

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 PreparationsIron- 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 onlyIron sucrose - IV use only Ferric carboxymaltose - IV use only Newer

Iron isomaltoside 1000 - IV use onlyFerumoxytol - 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 TYPE II TYPE III

TYPE IV

Example

Ferric carboxymalt oseIron dextran

Iron sucrose

Sodium ferricgluconate

Iron(III)-citrateIron(III)-sorbitolIron(III)-citrate + iron(III)-sorbitol + iron dextrinSodium ferric gluconate +iron sucrose

HMW ID LMW ID Iron Saccharate

Ferric Gluconate

Type of iron complex

IronIII-dextran

IronIII-dextran

IronIII-sucrose

IronIII-gluconate 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 IronSaccharate

Ferric Gluconate

pH 4.5 - 7.0 5.2 - 6.5 10.5 - 11.1 7.7 - 9.7

T½9.4 - 87.4 hr. (average 58.9 hr.)

5-20 hr. 6 hr. 1 hr.

Standard dosage

Injection time for undil. adm.

100 mg

2 min

100 - 200 mg

2 min or10 min

100 - 200 mg

5-10 min

125 mg

10 min

Maximum single dose

Infusion time/Injection time.

100 mg

2 minundil. adm.

20 mg/kg body weight

4-6 hrs. adm.

200 mg

10 min undil. adm.

125 mg

10 min undil. adm.

TDI adm. possible

Yes Yes No No

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

Safety ProfileMost 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 activationAlternate pathway complement activationDirect stimulation of mast cell degranulation

.

Controversies severe adverse allergic reactions with iron dextrancomponent 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 iron-binding capacity of parentral iron- More reactionMalnutrition & previous or simultaneous oral iron

therapyFolic 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 giveIM

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 IronDivided 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 half-lives, 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 ReactionsIncreased 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 Gluconate0.3% side effects with iron gluconate —very lowPts 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 SucroseNo 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 2-hour

session. This rate was associated with higher incidence of side effects such as nausea, hypotension, dizziness, and lower-back pain.

Adverse ReactionsExperienced in > 5% of patients:

Hypotension Cramps/leg crampsNausea Headache Vomiting Diarrhea

PrecautionsIron 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 antihistaminesor 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 ReactionsHypotension/flushingAssociated with rapid administrationNot associated with hypersensitivity reactionsResolves within 1-2 hours

PrecautionsIron 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 POLYMALTOSE500mg 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 IVIron-carbohydrate compounds interfere with clinical

laboratory determination of serum ironSerum 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 ErythropoetinInj 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 ErythropoetinUsed 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.

‘‘Transfusion should be Transfusion should be

prescribed prescribed ONLYONLY for conditions for conditions

for which there is for which there is NONO OTHER OTHER

TREATMENT’TREATMENT’

World Health Organization

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 40,000Non hemolytic febrile reactions 3-4%Anaphylactic reactions 1 in 20,000

GVHD 0.1 to 1%0.1 to 1%TRALI 0.1-0.2%0.1-0.2%HBV 1 in 50,0001 in 50,000HCV 1 in 3000 1 in 3000HIV 1 in 1,50,000 1 in 1,50,000

Summary Protocol of Severe Anemia in Pregnancy

Pregnancy < 30 weeks

Iron deficiency anemia

Folic acid deficiency

Oral irontherapy

Oral folatetherapy

Intolerance or non-compliance

Intramuscular iron

Intravenous iron

Summary Protocol of Severe Anemia in Pregnancy

Pregnancy 30-36 weeks

Iron deficiency

Folic acid deficiency

Parenteral iron

Oral folatetherapy

Intramuscular iron

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 oxygenationReasons 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

CONCLUSIONProper 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

NutritionControl of infestationControl of infectionIron and Folic acid supplementEconomic reformsEducationCultural reformsInfrastructure development, etc.

Severe Anemia

Management depends on the time at hand.If diagnosis:

Preconception - oral, if not tolerated, parenteralFirst & second trimester - oral + parenteralThird trimester - parenteral + blood transfusion by PCVLate in third trimester and/ labor, blood transfusion by

PCV nasal O2, B T, digitalization and ICU management with team approach.

Clinical conditionAssociated risk factors

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