Iron deficiency anemia is most common anemia during pregnancy whic needs careful evaluation and treatment by Dr Susanta Kumar Behera,Department of Obstetrics & Gynecology, MKCG Medical College, Brahmapur,ODISHA,INDIA
Anemia in pregnancy &role of parenteral iron therapy
ANEMIA IN PREGNANYANDROLE OF PARENTERAL IRON THERAPYDr SUSANTA KUMAR BEHERASENIOR RESIDENTDEPARTMENT OF O & GMKCG MEDICAL COLLEGEBRAHMAPUR, ODISHA; INDIA
Most Common Nutritional Disorder in the World Incidence = 40 to 60 % of pregnant women in India Commonest Medical(hematological) disorder duringpregnancy 25% of direct maternal deaths Responsible for 40% of maternal deaths in thirdworld countries. India contributes to 80% of maternal deaths due toanemia in South Asia
Pregnancy : Most dangerousjourney of mankindAnemia begins inchildhood, worsens duringadolescence in girls and getsaggravated during pregnancy
Quantitative or qualitative reduction of Hb or circulatingRBC’s or both resulting in a reduced oxygen carrying capacityof blood to organs and tissues Woman Hct 33% or Hb 11g/dl – 1st & 3rd trimester and Hct32% or Hb 10.5 g / dl in 2nd trimester(CDC/WHO)Gm% ICMR WHOMild 10 – 11 10-10.9Moderate 7 – 10 7-9.9Severe 4 – 7 <7Very severe < 4
• Plasma volume 50% (by 34weeks) but RBC massonly 25%• Disproportionate increase in plasma vol, RBC vol. andhemoglobin mass during pregnancyCRITERIA FOR PHYSIOLOGICAL ANAEMIA• Hb = 10 gm%• RBC = 3.2 million/mm3• PCV = 30%• Peripheral smear showing normal morphologyof RBC with central pallor
IRON REQUIREMENTS DURING PREGNANCYMaternal req. of total Iron -1000mg 500 mg Maternal Hb. Mass expansion 300 mg Fetus & Placenta 200mg Shed through gut., urine & skin 2.5mg /day in early pregnancy 5.5mg /day from 20 -32 weeks Average 4 mg/ day 6 – 8 mg/ day after 32 weeksIncreases from 1-2mg in 1st trimester to 6-8 mg in 3rdtrimester
Absorption of iron depends upona) Amount of iron in the dietb) Bioavailability of ironc) Physiological requirementsIron sources are two types1) Haem iron(5%) : hemoglobin and myoglobin from redmeat, poultry and fish2) Nonhaem iron(95%): fibers, green vegetables
NORMAL IRON CYCLEDietary ironUtilization UtilizationDuodenum(average, 1 - 2 mgper day)Muscle(myoglobin)(300 mg)Liver(1,000 mg)Bonemarrow(300 mg)Circulatingerythrocytes(hemoglobin)(1,800 mg)Reticuloendothelialmacrophages(600 mg)Sloughed mucosal cellsDesquamation/MenstruationOther blood loss(average, 1 - 2 mg per day)StorageironPlasmatransferrin(3 mg)Iron loss(Ferritin)(TIBC)
EFFECTS OF ANAEMA IN PREGNANCYANTEPARTUMa) Pre eclampsiab) Intercurrent infectionc) Cardiac failured) Preterm laboure) APHf) PIHINTRAPARTUM PPH Cardiac failure ShockPOSTPARTUMa) Puerperal sepsisb) Subinvolutionc) Failing lactationd) Puerperal venousthrombosise) Pulmonary embolism
Babya) IUGRb) Prematurityc) Increased risk of IDA early infancyd) Still birthse) Congenital malformationsf) ↑ in Neonatal deaths/Perinatal mortalityg) Intra uterine deaths(severe maternal anoxemia)h) Abnormal Social and Emotional behaviourEFFECT OF PREGNANCY IN ANAEMIA• Pt. Mildly anemic progresses to marked Anaemia• Pt. Who is severely anemic becomes symptomatic by theend of 2nd trimester
IDA IN PREGNANCYa) Grandmultib) Hook worm infestationc) Blood loss : Menorrhagia 20-30%d) Increase demand for iron particularly in 2nd & 3rd trimestere) Higher risk with morning sicknessf) Aspirin/NSAIDSg) Multiple pregnanciesh) Intolerance for red meati) Low dietary intake (Vegetarians, Vit. C & Calcium)j) Malabsorption (Hypo-or achlorohydria)k) Losses can increase with colorectal cancer, polyps
STAGES OF IRON DEFICIENCYPrelatent(Depletion) :a) Stores are depleted without a change in hematocrit orserum iron levels .b) Reduced stored iron e.g. serum ferritin with normalhemoglobinLatent(iron deficient erythropoisis) :a) Serum iron drops and the TIBC increases without a changein the hematocrit.b) Reduced stored and transport ironc) Increased erythrocyte protoporphyrin concentrationd) Detected by a routine check of the transferrin saturation.
Frank IDA :a) Associated with erythrocyte microcytosis andhypochromia.b) Stage of deficiency of stored, transport andfunctional ironc) Reduction of hemoglobin and serum ferritind) Low serum transferrin saturatione) Increased erythrocyte protoporphyrinconcentrationf) Iron deficiency attracts medical attention mostcommonly at this stage.
SYMPTOMS Fatigue Weakness Headache Loss of appetite Dysphagia Palpitations Dyspnea on exertion Ankle swelling Paresthesia Leukoplakia Cold intolerance irritabilityCLINICAL FEATURESSIGNS Glossitis Stomatitis Heart murmurs Increased JVP Tachycardia Tachypnea Postural hypotension Pallor Dryness or roughness of the skin Koilonychia Dry & cracked lips & Brittle hair
DIAGNOSIS OF IDA Low hemoglobin Low serum ferritin<15 mcg/dl Microcytic & hypochromic in absence of chronicdiseases/hemoglobinopathies Low serum iron content(< 30mcg/dL) Low PCV, MCV, MCH, MCHC High TIBC > 400 mcg/dl
• Serum iron < 50 μgm/dl• TIBC is increased - > 400 μgm/dl• Serum ferritin is < 12 μgm/dl• Serum transferrin saturation<20%• Red cell Zinc Protoporphyrin• Stainable iron in the bone marrow is reduced-Gold Standard• Serum transferrin receptor(TfR) : Increased• Bone marrow examination.• Reticulocyte hemoglobin conc. : Count of <26pg/ cell• LFT, RFT• Trial of iron therapy-diagnostic & therapeutic
TREATMENT Anaemic gravidas 120 –240mg / per day Supplementation with folic acid + Vit C. Ferrous sulphate 300mg TID daily after meals X 12months Therapeutic results after 3 weeks – rise in Hb % level of0.8gm/dl/ week with good compliance Rise in Hb at a rate of 2-4 gm/dl every 3 weeks tillnormal Hb conc. is normal after 6 wks of therapy
INDICATORS OF IRON THERAPYRESPONSE1. Increase in Reticulocyte count (Increases 3-5 daysafter initiation of therapy )2. Increase in Hb levels. Hb increases 0.3 to 1 g/ week3. Epithelial changes (esp tongue & nail ) revert tonormal
Pregnancy<30wksPregnancy30-36wksPregnancy>36wksIDA FAdef.Oral iron OralFAIntolerance orNon-complianceI/M iron I/VironIDA FA def.Parenteral OralFAI/M iron I/VironBloodtransfusion
ORAL IRON THERAPYWHO : 60 mg elemental iron + 250 ug FA OD/BD.Govt. of India : 100 mg Fe + 500 ug FA during 2ndhalf of pregnancy X 100 days.Drawbacks:- Intolerance- Unpredictable absorption rate.- Not suitable for patients with GI diseases/ significantbleeding- Non Compliant patient.- Long time for improvement
Side effectsa) Nausea & Vomitingb) Gastric irritationc) Constipationd) Abdominal crampe) DiarrhoeaResponse to therapy:- Sense of well being/Increased appetite.- Increase in Hb approximately 2gm% per every 3-4 wk- Reticulocytosis with in 5-10 days- hematocrit returning to normal.
Enteric coated/sustained release preparationsto be avoided as they are carried past duodenumlimiting absorption Once hemoglobin is normal therapy is continuedfor further 3 months /at least 6 wks postpartumto replenish stores.
Taking iron tablets Absorption helped by vitamin-C(take the tabletswith glass of orange juice) Take before or after 1 hr of meal Dont take tea/coffee/milk Calcium based antacids will reduce theabsorption
NEW THERAPEUTIC ALTERNATIVES• CARBONYL Iron• Iron ascorbateADVANTAGESa) Outstanding GI Toleranceb) Very safe with no poisoning even in high dosesc) No interaction with food stuffsd) Delicious with non-metallic taste and don’t stain thepatients’ teethe) Compliance is very high
INDICATIONSa) Failure to oral iron therapy.b) Non compliance/intolerance to oral ironc) 1st time seen during last 8-10 wks with severe anemiad) Malabsorbtion/IBDe) Small bowel resectionf) When hemorrhage is likely to continueg) C/I to blood transfusionh) Combination with recombinant human erythropoietini) C/I to oral therapyPARENTRAL THERAPY
Intravenous preparationa) Iron dextran (Imferon)b) Iron sucrosec) Sodium ferric gluconate (ferrlecit)Intramuscular preparationa) Iron Sorbitol Citrate in dextrin(Jectofer)b) Iron Dextran (imferon)Iron dextran: 50 mg/mL. Iron sucrose: 20 mg/mL. Ferricgluconate: 12.5 mg/mL
Contraindicationsa) h/o anaphylaxis to parenteral irontherapyb) 1st trimester of pregnancyc) Active acute/chronic infectiond) Chronic liver diseasesAdvantages:- Certainty of admission.- Hb rises @1gm/wk.Disadvantagea) Nausea and Vomitingb) Metallic taste on tongue
IM ROUTEIron Dextran (1ml contains 50mg elemental iron & 1amp=2ml)Dose : 100 mg IM OD/AD till the total dose overDrawbacks:a) Painful injection (less with jactofer).b) Skin discolorationc) Local abscessd) Allergic reactione) Fe over load.f) Category C drugg) Gluteal sarcomah) Test dose neededAdvantageCan be given in primary care set upAbsolute reticulocyte count increases in 7 daysHemoglobin increases within 1-2 wksWhole dose can be given in single setting
I/V Route :a) Repeated Injectionsb) Total dose infusionSide effects:- Anaphylactic reaction.- Chest pain, rigors, chills, fall in BP, dyspnoea, hemolysis.Treatment:a) Stop infusion.b) Give antihistaminics, corticosteroids & epinephrine.
IRON DEXTRANa) Colloidal solution of ferric oxyhydroxide complexed withpolymersised dextranb) Advantage : patients total iron requirement is given inone administrationc) Higher rate of adverse effects like delayedhypotension/ arthralgia/abdominal paind) Test dose is necessarye) Patients should be monitored 1 hr following a test doseof 25 mgf) Can given as IV infusion with rate less than 50 mg/ming) Category B drug
TDI – TOTAL DOSE INFUSIONI/V : (IRON DEXTRAN)TDI=(Normal Hb - Patients Hb) X Blood Volume(65ml/kg)X3.4100TDI= (Normal Hb – Pt. Hb) X Wt in Kg X 2.21+1000TDI=[10 × (target Hb-actual Hb ) × (0.24 × bodyweight )] +0/500Dose given I/V by slow push 100mg / day or the entire dosegiven in 500 ml N/S slow I/V infusion over 1-6 hours
FERRIC GLUCONATE COMPLEX IN SUCROSE1) Given as IV injection/infusion2) Standard dose of 125 mg may be given IV injectionover 10 min3) Rate should be < 12.5mg/min4) Dose can be repeated if ferritin < 100ng/ml orsaturation < 20%5) Can be safely given to Dextran sensitive patients
IRON SUCROSE• Commonly used in chronic kidney diseases• MW 34,000-60,000 D• Iron hydroxide sucrose complex in water• Given as IV injection/infusion• Each ml contains 20 mg of Fe• After IV administration it dissociates into iron &sucrose• T 1/2 is 6hrs• Category B drug
• Total iron deficit = Body weight x (Target Hb – Actual Hb) x 2.4 +Iron stores [mg]• Administered 100 mg IV over 5 minutes, thrice weeklyuntil 1000 mg• 200mg max dose per Sitting• Rate of administration should not more than 20 mg/min• Infusion : 50 mg to be injected slowly over 2 minutes,wait for 2-3 min ,then give another 50 mg over 2 min• 100mg-200 mg to be diluted with 100ml NS, infuse atleast 15 min• Marked increase in reticulocyte count expected in 7-14days
Advantages of IRON SUCROSE over othersa) All iron preparations were capable of causingtissue peroxidation except iron sucroseb) Less oxidative injuryc) Less risk of tissue parenchymal injury by free iron.d) Higher availability for erythropoiesis than ironDextrane) IV iron supplementation increases theerythropoiesis 5 timesf) Safe in dextran sensitive patientsg) Minimal side effects
The Hb rise will be evident in as early as 5 days IV iron sucrose is safe & effective Iron sucrose is given both bolus push & infusionDisadvantagea) Total dose administered in multiple infusionsb) Needs a set up where anaphylactic reaction canbe managed.
NEWEST FAST ACTING IV MOLECULESIron III Carboxymaltose (FERRINJECT) :a) Ferric hydroxide carbohydrate complex whichallows for control delivery of iron within cells ofthe RES (primarily bone marrow) and subsequentlydelivery to the iron binding proteins ferritin andtransferinb) T1/2 : 16 hrc) Dose : Single dose of 1000 mg over 15 minutes(maximum 15mg/kg by injection or 20 mg/kg byinfusion)
IRON III ISOMALTOSE(MONOFER)a) Strongly bound iron in spheroid iron-carbohydrateparticle providing slow release of bioavailale ironto iron binding proteinsb) Rapidly up taken by RES and little risk of free ironfor tissue damagec) Dose : 1000 mg in a single infusiond) Erythropoietic response seen within dayse) Serum ferritin returns to normal by 3 wks
FERUMOXYTOL USA FDA approved this drug in 2009 for ironreplacement in patients with IDA & CKD No test dose required Can be given as large dose (510 mg/vial) in <20Seconds in single settings No significant side effects Not approved in Europe
FAILURE TO RESPOND• Non compliance• Concomitant folate deficiency• Continuous loss of blood through hookworm infestationor bleeding haemorrhoids• Co-existing infection• Faulty iron absorption• Inaccurate diagnosis• Non iron deficiency microcytic anaemia
BLOOD TRANSFUSIONDecision based on• Needs and risk of developing complications of inadequateoxygenation• Both clinical and hematological groundsIndicationsa) Severe anemia, especially after 36 weeksb) Risk of further hemorrhagec) Associated infectionsd) Imminent cardiac compromise
Patient factors Type of surgeryPreg Preg Elective Emergency<36wks > 36wks C/S C/S-Hb ≤ 5gm% - Hb ≤ 6gm% - with H/o -assesswithout CHF without CHF APH,PPH, according-Hb 5-7gm%,if -Hb 6-8gm%,if previous to situationCHF, hypoxia, CHF, hypoxia, LSCSInfection infectionHb 8 – 10 gm%, confirm BG & cross-matchingHb <8 gm%, 2 units to be kept ready in OT
MANAGEMENT DURING LABOUR• Consideration for delivery in well equipped hospital.• Avoid sympathetic stimulation and hyperventilation;prevent rightward shift of ODC.• Supplemented with oxygen therapy• Prophylactic forceps/Vaccum to cut short 2nd stage• Decreased blood loss by active management of 3rdstage of labors.• Avoid maternal stress, patient can go into CHF.• PPH should be emergently treated(uterotonics)
ANAETHETIC CONSIDERATIONS Pre oxygenation is mandatory with 100% O2 Oxygen supplementation should be given in peri andpostoperative periods Blood arrangements prior to surgery is must Airway maintenance to prevent fall of PO2 due toairway obstruction Hyperventilation to be avoided to minimize respiratoryalkalosis General/spinal anaesthesia can be given after plateletcount and excluding h/o spontaneous hemorrhage.
MEGALOBLASTIC ANAEMIA• Incidence – 0.2 – 5 %• Caused by folic acid deficiency & Vit B12 deficiencyPathophysiology Preg. Causes 20 -30 fold increase in Folate requirement (150-450 microgram / day ) to meet needs of fetus & placenta. Placenta transports folate actively to fetus even if the motheris deficient. Vit.B12 deficiency : Occurs in patients with gastrectomy , ileitis,ileal resection, pernicious anaemia, intestinal parasites
FOLATE DEFICIENCY ANAEMIA Folic acid reduced to DHFA then THFA, used innucleic acid synthesis, is required for cell growth &division. So more active tissue reproduction & growth moredependant on supply of folic acid. So bone marrow and epithelial lining are therefore atparticular risk. Coexists with IDA
CLINICAL FEATURES• Insidious onset, mostly in last trimester• Anorexia and occasional diarrhea• Pallor of varying degree• Ulceration in mouth and tongue• Glossitis• Enlarged liver and spleen• Hemorrhagic patches under the skin and conjunctiva• Macrocytic Megaloblastic Anemia• Peripheral neuropathy• Subacute combined degeneration of the Spinal cord
a) Hb < 10gm%b) Hypersegmentation of neutrophilsc) Megaloblast, Howell-Jolly bodiesd) MCV > 100 fle) MCH > 33pg, but MCHC is Normalf) Serum Fe is Normal or high, TIBC is lowg) Serum Vit B12 levels < 100 pg /mlh) Radio active Vit B12 absorption test (Schilling Test)DIAGNOSIS
TREATMENT• Replace iron and treat underlying disease.• Oral route is preferred for replacement.• Response can be followed by retic. increase in 1-2weeks (5-7 days)• Hb response to treatment– half normal by a month– returns to normal by 2-4 months
• Replacement therapy is prolonged by 6-12 months toreplenish stores of iron.• 1000 microgram Parenteral Cyanocobalamin everywk X 6 weeks• Prophylactic : All woman of reproductive age shouldbe given 400mcg of folic acid daily• Curative : Daily administration of Folic acid 4mgorally up to at least 4 wks following delivery
MANAGEMENT Multidisciplinary approch Routine BP measurement and urinalysis to detecthypertension and proteinuria Retinal screening/fundoscopy for prliferativeretinopathy Screening for iron overload(serum ferritin) Screening for PAH by echocardiography Antibiotic prophylaxis-penicillin/eruthromycin Termination planned for homozygous state
Folic acid-5 mg should be given ODpreconceptually and throughout the pregnancy Hydroxurea if taking should be stopped 3 monthsprior conception ACE inhibitors & angiotensin receptor blockersstopped before conception Early detection and treatment of malaria andinfections Low dose Aspirin from 12 wks of gestation
Thromboprophylaxis with LMWH NSAIDS between 12 to 28 weeks Fluid and oxygen therapy(oxygen saturation > 95%) inpainful crisis BT indicated only during complications like acuteanemia/ACS/twin pregnancies, preeclampsia,septicemia, renal failure Goals : Hb > 8gm/dl & HbA > 40% of total Hb Iron therapy to be given if there is evidence of irondeficieny
• Vaccine : H influenza type b, conjugatedmenigococcal C vaccine, peneumococcal vaccine &Hepatitis-B vaccine• Timing of deliver : 38 -40 wks of gestation eitherby induction of labour/elective CS• Factors to be avoided favouring sickling- Dehydration- Hypotension- Hypothermia- Acidosis- High conc. of HbS
CS is preferred over vaginal delivery when labour isnot progressing well. Continuous FHR monitoring due to increases rate ofstill births/abruption/compromosed placental reserve Counseling the parents regarding partner screeningfor carrier detection. Contraceptivesa) Porgesterone only pillb) Injectable contraceptivesc) LNG-IUSd) Barrier methodse) Sterilization
THALASSAEMIAS• The synthesis of globin chain is partially or completelysuppressed resulting in reduced Hb. content in redcells,which then have shortened life span.• TYPES:- Alpha thalassaemia.- Beta thalassaemia: Major & Minor• Microcytic haemolytic anaemias• Reduced synthesis of one or more of polypeptide globinchains.• Higher transfusion requirements in pregnancy worsenhaemosiderosis & cardiac failure.
CLINICAL FEATURES• Usually asymptomatic• Weakness, fatigue, exhaustion, loss of appetite, indigestion,giddiness, breathlessness• Palpitations, tachycardia, breathlessness, increased cardiacoutput, cardiac failure, generalised anasarca, pulmonary edemaa) Pallorb) Nail changesc) Cheilosis, Glossitis, Stomatitisd) Edemae) Hyperdynamic circulation (short & soft systolic murmur)f) Fine crepitations
Women with hemoglobinopathy should be offered oraliron therapy if serum ferritin<30 mcg/L Referral to secondary/tertiary care to be done ifa) Severe anemiab) Significant symptomsc) Late gestation(34 wks)d) Failure to respond to oral ironTREATMENT
WHO - 60 mg Elemental iron + 400 micro gramFolic acid / day up to 3 months postpartum GOI - 60 mg elemental Iron + 500 mcg Folic acidas Prophylactic supplementation x 100 days in 2ndtrimester up to 3 months postpartum
ANAEMIA ASSOC. WITH CHRONICINFECTIONS / DISEASE• Common in developing countries• Poor response to Haematinics unless primary cause istreated• Worm infestations is common ( Diagnosed by stoolexamination )• Urinary tract inf, & asymptomatic bacteriuria in preg.is assoc. with refractory anaemia• Chronic renal disorders = due to erythropoietin def.
• Identifying the etiology and treat accordingly• Deworming with mebendazole/albendazole/levamisole• Treated with recombinant Erythropoietin for renaldisease.• ATT to a patients with tuberculosis• Antibiotics to treat UTI according to sensitivityTREATMENT
PREVENTION• Dietary advice and modification(red meat/ poultry/fish)• Germination and fermentation of cereals and legumesimprove the bioavailability of iron in food• Green peas/Whole wheat/Green vegetables/Jaggery• Iron supplementation of adolescent girls & non pregnantwomen• A nutritious diet in a pregnant woman should beproviding about 40 mg elemental iron daily.
• Food fortificationa) Fortification of staple food like wheat flour which istechnically simple(USA)b) Fortification of curry powder, salt and sugar, driedand liquid milk(SA)c) Fortification of infant foods (INDIA)d) Fortification of complimentary foods (USA)
Treatment of hookworm Infestation, malaria,TB Avoidance of Hypoxia, Acidosis, Infection, DehydrationStress , Exercise, Extreme, Temperature Avoidance of frequent child birth. Supplemented Viamin-C (250-500mg/day) with iron Adequate treatment for any infection like UTI
Early detection of falling Hb level, levels should beestimated at 1st A/N visit, 30th & finally 36th week Mandatory monthly screening for anemia should bedone in all antenatal clinics(especially at booking and at28 wks with FBC) Screening and effective management of obstetric andsystemic problems in all pregnant women