Anemia Pregnancy (3)

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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 UniversityGwalior, M.P.

Dr Sonali AgrawalDGO

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



Anemia is a sign, not a diseaseof 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 ofmaternal 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 acidand/or vitamin B12

Dimorphic and protein deficiency anemia (30%) inextreme 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, chronicrenal 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 Hypervolemia1. To meet the demands of the enlarged uteruswith its greatly hypertrophied vascular system.

2. To protect the mother, and in turn the fetus,against the deleterious effects of impairedvenous return in the supine and erect positions.

3. To safeguard the mother against the adverseeffects 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 theprevalence of anemia to be 70-80% in children, 70% inpregnant 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% duringthe 1st trimester & < 10.5 gm/dl Hct < 32% during the2nd trimester

Absolute iron deficiency is defined as ferritin <200µg/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%



Normal Iron

depletion

Iron

deficient

erythropoiesis

Iron

deficiency

anemia

Storage 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 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 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 Requirements Iron requirement for normal pregnancy is 1gm

200 mg is excreted300 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

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 absorbthis 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 thedemands.

Therefore, iron supplementation during pregnancy isrecommended universally even in non anemic women.



Maternal Anemia:A Preventable Killer



Decreasedabsorption

Increasedblood loss

Poor diet

Increased

requirements

Causes ofIDA



Anemia: Etiologies Inadequate dietary intake

Poor nutrition

Chronic alcoholism

Decreased consumption ofanimal protein and ascorbicacid

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 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 significanteffects.

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 BayleyMental 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 hypoxiadevelops, which leads to stimulation of fetalerythropoiesis

• 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

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 ACTHand cortisol

Abnormal trophoblast invasion andrelease 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 lowperformance of eachorgan.

• 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-partumand puerperal sepsis.

Negative thermoregulation

Increased risk of bloodtransfusion

• Preterm Labor

• Sub involution• Failing lactation

• Pulmonary Venous:thrombosis & embolism,

due to thrombophlebitis.



ANTENATAL CARE

As a routine - No differenceRegistration

Counseling

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

I M



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. immediatelypostpartum

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 AnemiaSymptoms:

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 AnemiaSigns:

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% ofhemolytic 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 indicateabsence of stored iron, <20 or <15 µg/L indicate depleted iron stores

Transferrin saturation (TSAT), should be above 16% with normalbeing 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 isbelow 70fl

Serum iron - decreased in a variety of states includingiron deficiency, inflammation & stress. Variestremendously from morning to evening and from day today. value < 0.5mg/L indicate anemia, normal range:0.80 to 1.80 mg/L

Total iron binding capacity is very specific for irondeficiency (near 100%) but has poor sensitivity (<30%).

Iron saturation (Fe/TIBC x 100) can be decreased below16% 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; increasedby 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 depletiondoes not prove IDA



Specific tests for etiology of the anemia

•Urine & stool examination• Test for malaria• Rarely- Endoscopic or barium studies of the GItract, bone marrow examination

Exclude other causes of hypochromic microcyticanemia

•Anemia of chronic disease• Thalassaemia trait

• Sideroblastic anemia

L b T ti f



Lab Testing forIron Deficiency Anemia (IDA)

Patient with anemia,

Ferritin

> 100

Ferritin

20-100

Ferritin < 20,

or Iron < 50

and IBC > 450

Ferritin > 20,

or Iron > 50

and 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 modification

Iron supplementation of adolescent & non pregnantfemale

Tx of Hookworm infestation Control of malaria

Iron supplementation in pregnant Women

Food fortification

Antenatal care for early recognition Optimal birth spacing

E f d h



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 absorptionmore 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?



Inorganic1. Ferrous

• sulfate, fumarate, gluconate, ascorbate, succinate,glutamate, dextran, carbonyl iron, and lactate

• bis-glycinate chelate.

2. Ferric Salts – iron (III)-hydroxide polymaltosecomplex

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 thetolerance, side effects, clinical situation of the pt andavailability of a particular salt.

• Fe sulphate is cheapest, best absorbed, and mostcommonly prescribed, showing a rapid rise in both serumiron 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 hascome 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 presenceof 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 mostchildren



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 asdocusate, 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. notdissolve in the stomach hence not absorbed in duodenum or upper jejunum

Ascorbic acid is enhanced absorption by forming a chelate with ferriciron at acid pH that remains soluble at the alkaline pH of theduodenum. & reverse the inhibiting effects of substances such as teaand 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 - decreasedabsorption 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 afterinitiation 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 compliance2. 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 deficiencyc. Lead poisoning

d. Sideroblastic anemia

e. AtransferrinemiaPrema 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 ironstores

Follow up



Follow up:

Iron status (ferritin, TIBC, & TSAT) and RBC indicesmust be checked periodically to re-evaluate the pt'sneed for additional iron supplementation.

Parenteral iron should not be administered topatients with ferritin > 800 ng/mL or transferrinsaturation > 50%.

P t l I Th



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 hadsignificant 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:



Contraindications:

Hypersensitivity to any of the Parenteral ironproducts

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 parenteraltherapy.

Emergency measures like injection hydrocortisoneadrenaline, oxygen cylinder etc., should be keptready.

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 yetapproved 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 –8days 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 Ferriccarboxymalt

ose Iron dextran

Ironsucrose

Sodiumferric

gluconate

Iron(III)-citrateIron(III)-sorbitol

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



HMW ID LMW ID Iron

Saccharate

Ferric

Gluconate

Type of ironcomplex

IronIII-dextran

IronIII-dextran

IronIII-sucrose

IronIII-gluconate insucrose

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 alcoholper ml

Relativestability of iron complex

Robust/

strong

Robust/

strong

Half robust/mediumstrong

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 Ferric



Saccharate 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 58.9hr.)

5-20 hr. 6 hr. 1 hr.

Standarddosage

Injection timefor undil. adm.

100 mg

2 min

100 - 200 mg

2 min or

10 min

100 - 200 mg

5-10 min

125 mg

10 min

Maximumsingle dose

Infusion

time/Injectiontime.

100 mg

2 minundil. adm.

20 mg/kgbody 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 doseof 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



y g p , yintravascular fluid compartment

Within Phagocytes of RES,Fe released from the iron-carbohydrate compound into anLMW 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 erythroidprecursors.

Transferrin delivers iron to transferrin receptors on the surface of erythroidprecursors.

Iron-transferrin-transferrin receptor complex supplies Fe for Hb synthesis &maturation of the red cell



Safety ProfileMost of the iron is deposited in the Reticulo-endothelial

system than in parenchyma.

This gives the advantage of not having free-radicalinduced lipid peroxidation which takes place withinparenchyma only.

Practically no liver injuries occur as confirmed byexperimental histological results.

Iron dextran has the highest incidence of modest andsevere life-threatening side effects.

Hypersensitivity Reactions:



Hypersensitivity Reactions: Anaphylactic reactions

Almost exclusively with iron dextran, independent ofdose - 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 developingundesired 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 (morelikely to occur when using iron sorbitol – citric acid

complex, since the iron is less firmly bound than withiron dextran (Meyler 14th edition, page 701).

Conditions associated with low iron-



binding 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 theircomparative 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 associatedwith anaphylactoid type reactions, dose related.

Reactions were due to over saturation of thetransferrin molecule resulting in the circulation offree iron.

This theory is still uncertain.



Iron sucrose is also associated with

anaphylactoid type reactions, but these seem tobe dose related

Reactions that occur are due to over saturationof 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 recombinanthuman 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



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 anemiaof 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 half-lives, respectively, could be given as frequently asevery 24 hours.

Total Dose infusion



INTRAVENOUS IRON THERAPY

Iron Dextran –

Test dose (25 mg Fe) is required. Diluted in 50-100 mL ofNS 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 4to 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 or100-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 tohigh 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 tohave a reaction to iron gluconate than to iron sucrose.

Adverse reactions with iron sucrose or gluconate seen athigher 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; irongluconate can only be given at 300 mg/4 hours.

Iron Sucrose



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 usedsafely.

Doses as 500 mg have been infused in a single 2-hour session. This rate was associated with higherincidence 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 notexceeding 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 30minutes, then 80mls/hr.

Or 1000mg in 200mls 0.9% NS.Run at 20mls/hr for30 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 oflegs/hands/face)

Chest pain/back pain

Rash

Laboratory Testing after IV



Laboratory Testing after IV

Iron-carbohydrate compounds interfere with clinicallaboratory determination of serum iron

Serum iron & transferrin saturation should be testedafter 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 ora 100-mg dose of iron sucrose.

One month for ferritin or iron studies after a 500-mgdose 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 bekept ready.

Produces 3gm % rise in Hb over a 2wk period



Inj erythropoietin 18000u s/c in one dose & inj lowmolecular dextran 500mg to be dissolved in 500mlof dextrose to be given over 2 hours, as slow iv



Indication of Erythropoetin

Used in severe anemia & renal failure for significantincrease in Hb and to avoid Blood transfusion.

Gynaecological surgeries: preop use of erythropoietinand Parenteral iron has shown to avoid the need forblood transfusion later.



‘Transfusion should be prescribed

ONLY for conditions for which there

is NO OTHER 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 dueto religious beliefs.

• S/E of BT-

• HIV, Hepatitis B, C, malaria, rubella, etc.

• Transfusion reaction

• Risk of incorrect cross - matching and transfusionnegative impact on immune system.

• .

d f l d f



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

http://www.suht.nhs.uk/ideal/media/images/e/7/blood_transfusion_2.jpg



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

Parenteraliron

Oral folatetherapy

Intramuscular

iron

Intravenous

iron

Pregnancy >36 weeks

Blood transfusion

Key Points of



y

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, andgiving iron supplements.

Eating a well-balanced diet rich in iron and vitamins can prevent.

Can be successfully treated

CONCLUSION



CONCLUSION

Proper antenatal care and awareness programmes forprevention of anemia.

Adequate iron / folic acid prophylaxis in all antenatalcases.

Early detection and timely referral to tertiary centers.

Management to be decided depending upon the cause ofanemia, 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 anycontraceptive 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



Severe Anemia

Management depends on the time at hand.

If diagnosis:

Preconception - oral, if not tolerated, parenteral

First & second trimester - oral + parenteralThird trimester - parenteral + blood transfusion by PCV

Late in third trimester and/ labor, blood transfusion byPCV nasal O2, B T, digitalization and ICU

management with team approach. Clinical condition

Associated risk factors



Motherhood . . .. . . A dream of every woman

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Anemia Pregnancy (3)