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