ANAEMIA IN PREGNANCY

Prof. M.C.Bansal.

MBBS., MD. MICOG. FICOG.

Founder Principal And Controller

Jhalawar Medical college & Hospital Jhalwar.

Ex Principal & controller MGMC & Hospital Sitapura ,Jaipur.

ANAMIA IN PREGNANCY.

Commonest medical disorder in pregnancy.

18-20 pregnant women are anaemic in developed countries as compared to 40-75 % in developing countries .

It is responsible(directly / contributory factor ) for significant high maternal and fetal mortality and mortality throught out world , but more so in developing nations.

WHO DEFINITION OF ANAEMIA IN PREGNANCY For diagnosis of anaemia in Pregnancy when HB

concentration is < 11 gm% ( 7.45mmol/ L)and a haematocrit of < 0.33.

Mild------------ 8 – 10 mg % Moderate ---- 5 –< 8 mg % Severe---------- < 5 mg % During Pregnancy there is increase in total blood volume

(1500 ml = 30 - 40%), plasma volume(250 ml = 40-50 %) as well as the EBC volume (350ml = 20 -30 % ) also ,

But increment in plasma volume is more then the increased total hemoglobin(15-20 % ).

Hence there is dilution of blood, resulting in physiological anaemia( upper limit for normal / 100% Hb level in pregnancy is brought down to 11gm % ) .

SOURCES OF VARIOUS NUTRIENT REQUIRED FOR ERYTHROPOESIS

Nutrients Sources

Iron Haem Iron :Animal blood , flesh , viscera ( live Kidney , red meat , poultry and fish ( including muscles ) Non Harem Iron : green leafy vegetables, cereals , seeds , Vegetables ( peas , backed beans ) roots and tubes , japery , Cooking in iron vessels < urinal , Dates etc .

Folic Acid Green Vegetables ( palak, Maithy , bathali , Broccoli ) Fruits , Germinate wheat , Liver and Kidney.

Cyanocobalamin ( Vit B12 ) Meat , fish , eggs , milk

Ascorbic Acid ( vit. C ) Citrus fruits , Amala ( indian gooseberry )

Other Vit,B Green leafy vegetables and fruits

IRON

Iron is a critical element in the function of cells,

Body should protect itself from ill effect of excessive iron as it is highly toxic ,as it generates free radicals such as singlet O2 / OH +

Major role of iron (ferrous form ) is to carry O2 as part of hemoglobin . O2 is also bound by myoglobin An iron compound present in muscles.

Iron is a critical element of iron containing enzymes including cytochrome system in mitochondria.

IRON DISTRIBUTION IN BODY. iron content in mg.

Adult male Adult Female

80 Kg 60 Kg

Hb(65%) 2500 1700

Myoglobin (4%) & 500 300

Enzymes

Transferretin iron 3 3

(0.1%)

Iron Stores 600- 1000 0- 500

(15-30%)

IRON ABSORPTION & TRANSPORT Ingested Iron- ferric form is changed to Ferrous

form by gastric HCl acid ,. It reaches in duodenum . Liver secretes Appoferrin in bile . Appoferrin combines with ferrous ion in duodenum

to form Transferrin. Transferrin attach to receptors present on intestinal

mucosa . Transferrin get absorbed in intestinal mucosa by

pinocytosis . Then transferrin is released in plasma to plasma

transferrin. Transferrin is circulated to tissue –the loosely

bound iron is released to tissue where it is needed.

IRON TRANSPORT AND METABOLISM

Most part of excess of iron is stored in hepatocytes of liver and a little of it in RE cells.

The unique characteristic of transferrin is that it bounds strongly to the receptors present on the cell membrane of erythroblasts present in bone marrow.

Endocytes in erythroblasts ingest the bound form of iron .

Apoferrin directly delivers iron molecule to mitochondria where heam chain is synthesized.

IRON TRANSPORT AND METABOLISM

RED BLOOD CELLS Shape & Size –RBC are biconcave disc with 7.5 um

in diameter and 2.5 um in thickness at periphery but < 1um at center.

Concentration in blood --- 5.2 mill/ cmm in man. 4.7 – 5.0 mill / cmm in female. Hb Content in RBC ----RBC are able to concentrate

Hb in it cellular fluid up to 34 gm / ml of RBC. Hb concentration in whole blood --- 14-15 gm % / ml in man 13.5 -14 gm % /ml in female. Each Gm of HB is able to combine with 1.3ml of

O2 ., there by 100 ml of blood with normal Hb content can absorb 20 ml and 19 ml of O2 in man and female respectively.

RBC PRODUCTION--ERYTHROPOESIS

Erythropoesis starts in embryonic life in yolk sac from pluripotent stem cells the original pluripotent haemopoetic stem cells.

In later foetal life it occurs mainly in red cells in liver spleen and bone marrow.

In neonatal life and child hood it occurs in bone marrow of all the bones and liver.

In adults all types of blood cell production occur in bone marrow present in membranous bones e.g. vertebra, sternum , ribs and iliac crest and proximal ends of long bones.

Pluripotent stem cells differentiate in to pro - erythroblasts—the parent cell of RBC.

Growth inducers and differentiation inducers produced locally in bone marrow play a major role in production of RBC and other cells.

HAEMOPOESIS

REGULATORY FACTORS OF ERYTHROPOESIS

Erythropoetin ----90 % produced by renal tubular epithelium ., hypoxia or < P O2 level stimulates its production. 10 % is produced in liver .

Nore epinephrin, epinephrin and PGS accentuate development maturation of RBC after the pro-erythroblast(from haemopoetic stem cells ) stage of production which takes about 5 days and is under growth inducers in bone marrow.

Low tissue O2 concentration ---as in high altitudes, chronic blood loss , cardiac failure and chronic lung disease etc.

Increased demand for o2 carrying capacity –as in pregnancy.

FUNCTION OF ERYTHROPOIETIN MECHANISM

MATURATION OF RBC---- It requires vit B 12 and Folic acid ---- Vit. B12 and Folic Acid are accential for

production of DNA . Thyomidine Triphosphate is an important

building block Of DNA. The deficiency of Vit B12 and Folic acid

leads to maturation failure of RBC , resulting in megaloblast production.

These immature cells when appear in blood circulation, serve no purpose of O2 transportation as efficiently as mature RBC. Their life span is also small hence person develops anaemia.

HEMOGLOBIN SYNTHESIS----- Synthesis of Hb starts in proerythroblasts

and continues even in reticulocyte stage. First Succinyl –CoA is formed in Krebs

metabolic cycle . It combines with a molecule of glycine to form Pyrole molecule .

4 molecules of Pyrole combine to form Protoporphyrrin IX .

Protoporphirrin IX combines with Ferrous molecule to form Heam .

Haem combines with Globin and Hemoglobin chains (alpha & beta ) are produced.

HEMOGLOBIN SYNTHESIS---

Depending upon presence or absence of amino acid combination in poly peptide part of Globing ,. There are different types of Hob chains---like alpha, beta , gama and delta.

Adult Hb is Hb A and has 4 chains 2 alpha & 2 beta chains.

Each HB chain has a Heam prosthetic group containing an Iron ion.

One HB molecule has 4 Heam chains and 4 iron ions capable of absorbing 8 atoms of Oxygen.

4 F + 8 o = 4 FO2(4 molecules of Ferrous Oxide contain 4 molecules of iron and 4 molecules / 8 atoms of oxygen )

STRUCTURE OF HAEMOGLOBIN

LIFE SPAN OF RBC AND ITS DESTRUCTION --- Mature RBC circulate and remain alive

( active ) for 120 days . RBC face bear and tear in circulation and

get aged when they are engulfed by macrocyte macrophages which dissociate iron from haem .

This iron is mainly stored in ferritin pool for Hb production .

Rest heam is denaturized in liver as bilrubin. Daily loss of Iron-0.6 mg iron is lost in feces

by male ,. But iron loss is more in menstruating females (1.3 mg).

TYPES OF ANAEMIA DURING PREGNANCY 1 . Hereditary causes Thalassaemias , Sickle Cell

Haemoglobinopathies , Haemolytic anaemias , other type of Haemgobinopathies.

2 .Acquired Causes A . Nutritional---Iron deficiency anaemia ( microcytic

hypocromic anaaemia , Folate deficiency anaemia ( megaloblastic anaemia ) , Vit B 12 Deficiency anaemia ( Megaloblastic anaemia )

B . Anaemia due to bone marrow failure ( aplstic / hypo plastic anaemia ).

C . Anaemia secondary to inflammation , chronic disease , malignancy.

D . Anemia due to acute / chronic blood loss. E . Acquire hemolytic anemia. Note Iron Deficiency anemia is most common in developing

countries like ours

IRON DEFICIENCY ANAEMIA (IDA) This Is Most Common Type Of

Anaemia. Hematologicaly described as Microcytic

Hypochromic Anaemia . More common in developing countries

owing to Low Dietary Intake Of Iron , Chronic Intestinal Diseases Like Amoebiasis, Sprue, Diarrhoea, Parasitic Infestation (Hook Worm)

Malaria , Schistosomiasis , Phytates In Diet,chronic Blood Loss ( Menorrhagia , Piles, Fissure In Ano ---Apathy To Take Treatment) Too many and too frequent pregnancies and plural pregnancy.

CLINICAL FEATURES OF ANAEMIA IN PREGNANCY Symptoms Signs

Weakness Pallor .

Lassitude , tiredness , exhaustion Glossitis .

Indigestion Stomatitis .

Loss of appetite Oedema

Palpitation Hypoproteinaemia .

Breathlessness Soft systolic murmur in mitral area due to hyperdynamic circulation

Giddiness / dizziness Fine crepitations at lung bases.

Swelling feet eye lids ( peripheral )

Pale nails . Platynaechoea . Koilonaechia

Generalized anasarca. Tenderness in sternum .

Blackouts in front of eyes on sudden standing

Hepatic –splenic enlargement .

Symptoms of congestive cardiac failure

EFFECTS OF ANAEMIA ON PREGNANCY .

Maternal Foetal

Weakness Preterm baby

Lack of energy Small for gestation

Fatigue PET

Increased perinatal morbidity and mortality

Poor work performance Iron deficiency

Palpitation tachycardia

Cognitive and affective dysfunction in the infant

Even mild bleeding in APH or PPH can endanger the life

Increased incidence of diabetes and cardiac disease in later life

Breathlessness

Increase cardiac output

Cardiac decomposition

Cardiac failure

Increased incidence of preterm labour

Sepsis

DIAGNOSIS OF IDACharacteristics Calculation Normal

Range IDA

Hb gm % Sahli’s method

11-15 < 11

Mean corpuscular volume(MCV) PCV/RBC 75-96 <75

Mean corpuscular HB Hb /RBC 27-33 <27

Mean corpuscular Hb Conc. (g/dl) HB / PCV 32-35 <32

PBF(peripheral Blood Film ) Normocytic Normochromic

Microcytic Hypochromic

Serum Iron (ug/dl) 60 -120 < 60

Total iron binding capacity (ug/dl )

300- 400 >350

Transferrin Saturation < 15%

Serum Ferritin (mcg / dl ) 13-27 <12

Free erythrocyte protophyrin (ug/ml)

<35 >50

Serum Transferrin Receptors increased

TREATMENT OF IDA In average pregnancy , iron the requirement are : Basal iron –280mg. Expansion of Red Cell Mass –570 mg . Fetal transfer ----200-350 mg. placental---------- 50 -150mg. blood loss at Delivery ---100-250 mg. After deducting iron conserved by amenorrhoea

( 240-480mg. ) , an additional 500-600mg .

Of iron is required in pregnancy . if she is chronically anaemic then her iron stores are also depleted., hence 500mg more elemental iron is to be prescribed.

There by total iron requirement will be 1000 mg .

PROPHYLAXIS---- Extra iron requirement in pregnancy can be met with

balanced diet rich in iron containing food . Avoid food containing Phytates , tannins (tea –coffee)known inhibitors of iron absorption

4-6mg elemental iron if absorbed / day during 2nd and 3rd trimester ( over period of 1oo days ). Average daily requirement of absorbed iron is 4m., beng2.5 mg/day in early 1/2 , 5.5mg/day during 20- 32 weeks and 6-8mg / day 1fter 32 weeks onwards of gestational period.

Indian Government has recommended to prescribe Tab Ferrous sulfate 100mg + 500ug Folic acid / day for 100 days .

As hook worm infestation is common , 400mg single dose Albendazole or Mebendazole 100mg B.D. for 3days therapy is also recommended.

TREATMENT OF IDA----ORAL IRON 1. When anaemia is of mild to moderate degree and there

is plenty of time (> 30days) before EDD., oral iron therapy with 200 mg elemental iron with 5mg Folic acid / day will improve the Hb by 0.8 gm in a week . Reticulocyte count start to increase with in 10 days after starting oral iron therapy .

Side effects (10-40% cases ) will develop mainly related to GIT such as , nausea , vomiting , epigastric burning , constipation abdominal cramps and diarrhoea.

There is no scientific evidence that any particular brand is better .

Slow release preparations are associated with less side effect , but manly due to slow / decreased iron absorption . Taking iron with ascorbic acid will decrease the GIT side effects.

Those who can not tolerate oral iron , carbonyl iron can be started.

There is no advantage in using parenteral iron over oral iron , if oral iron is tolerated and there is plenty of time is available.

IRON PREPARATIONS AVAILABLE

IRON PREPARATION

ELEMENTAL IRON CONTENT (mg%) DOSE in mg

Ferrous Fumerate 30 200

Ferrous Gluconate 11 550

Ferrous Sulphate 20 300

TREATMENT OF IDA --- PARENTERAL THERAPY In moderate anemic , pregnancy near term ( 32-

34 weeks) , or oral iron is not tolerated ---- parenteral Iron therapy should be considered .

total Iron Dose calculation Elemental iron (mg) = Normal HB – Pt’s HB

(gm%) x pt’s weight in KG x 2,2 + 1000

Preparations Iron Sorbitol Injection– given deep IM after

sensitivity test –rapid absorption owing to molecular wt., associated with pain and skin discoloration at the site of injection .Total

calculated dose is given over 2 weeks of duration.

PAENTERAL IRON THERAPY ---- Iron Dextran – can be given IM / IV

route after sensitivity test . It has minimal side effects ,as it is highly fractionated low molecular salt .

Iron Sucrose – can be given as single / repeat dose in Iv drip.

Parenteral therapy will take 4-6 weeks to reach their optimal effect.

ANEMIA AND BLOOD TRANSFUSION -- When Hb is < 5gm % and or pt is near

term and obstetrical haemorrhage . Digitilisation and Lasix therapy may be

given to control CHF or to prevent its precipitation.

PCV transfusion , if available is preferred than Whole Blood .

Recombinant Erythropietin can be used along with parenteral iron therapy to the patients having chronic renal disease complicating pregnancy and to non responders to oral / parenteral iron therapy.

FOLATE DEFICIENCY ANAEMIA ---

Folic acid is needed in higher doses during pregnancy because of the increased cell replication , taking place in fetus , uterus and bone marrow.

800 ug is required / day , but pre existing deficiency is common especially in developing countries . It is mainly due to inadequate diet / intestinal malabsorption( sprue ) syndrome .

More common in twin pregnancy , multigravida , hook worm infestation , GIT diseases , bleeding piles , Haemolytic conditions , malaria and other infections .

Anti folate medications like anti epileptics , anti cancer .

Combined iron and folic acid deficiency anemia is common in developing countries.

FOLIC ACID DEFICIENCY ANAEMIA -- Symptoms Asymptomatic , loss of appetite,

vomiting , diarrhoea, unwell with unexplained fever Signs Pallor Bleeding points on skin , Enlarged

spleen and liver and neuropathy. Maternal complications PIH, Abruptio

placenta . fetal complications Folate deficiency in

mother can cause fetal neural tube defects , abortion , IUGR, premature / small for date fetus and poor folate level in newborn .

DIAGNOSIS OF FOLIC ACID DEFICIENCY ANAEMIACharacteristics Normal range Folic acid deficiency

Hb 11-15gm% <11 gm%

MCV 75-96 > 96

Mean corpuscular HB

27 - 33 33

Mean corpuscular HB Conc.

32-35 Normal

PBF Normocytic Normochromic

Megalobastic , neutropenia , thrombocytopenia, hypersegmentation of neutrophills

Serum Folate >3 <3

Red cell Folate

>150 ng / ml < 150

Serum Iron 60-120 ug/dl Normal

Serum lactate dehydogenaseHomoCysteine

Increased

Increased

TREATMENT WHO recommends 800ug / day in pregnancy and 600ug / day during

lactation period . To meet this need pregnant and lactating

women should be encouraged to eat more green leafy vegetables ( palak , maithi , baithali , brocoli ) and offal ( liver and kidneys .

Treatment for patient with Folic acid deficiency anaemia should take 5mg folic acid / day for > 4 weeks . Response is observed by fall in LDH

level in 3-4 days and increase in reticulocyte count in 5-8 days.

CYANOCOBALAMIN (VIT .B12 ) DEFICIENCY

A rare cause of anaemia in pregnancy . , as daily requirement of 3ug is easily met with a normal diet .

Pernicious anaemia due to absence of intrinsic factor , resulting in decrease absorption of Vit B12 is rare in pregnancy ., as it usually causes infertility.

Clinical findings are same as in folic deficiency . Vit B12 level is lower in the blood ( < 90ug / L)

Deoxyuridine test can differentiate in two . Parenteral Vit B12(cynocobalamin ) 250ug / month

is the treatment. Gastric mucosal atrophy following long term use of

H2 inhibitor and Proton pump inhibiting anta acid will result in deficiency of intrinsic factor and decreased absorption of Vit B12 .

MEGALOBLASTIC ANAEMIA PBF AND BONE MARROW

HAEMOGLOBINOPATHIES

Each molecule of normal Hb is composed of 4 subunits , with a single heam group and 4 species specific globin chains .

2 pairs of globin chains ( 2 alpha & 2

Beta chains ) are attached to the Pyrole rings to make normal Hb . The integrity of the Heam moety and amino acid sequence of globin chain determine the structure of the globin chain and interaction between the 4 sub units of the Hb .

THALASSAEMIA Characterized by impaired of one or more of globin

chains . ALPHA Thalassaemia when alpha chains are

impaired . If only one alpha chain is impaired the it is called Alpha Thalassaemia Trait.

Beta thalassaemia When both Beta chains are impaired. Beta Thalassaemia Trait if only one Beta chain is impaired.

Children With Beta Talassaemia usually die before reaching reproductive age . Repeated blood transfusion and Iron chelating therapy some women remain alive , get married and become pregnant. These women suffer from chronic anaemia which need to be differentiated from IDA., by Blood indices and Hb F and HbA 2 Levels .

D/D OF IDA & THALASSAEMIA

Characteristics

Normal Range

IDA Thalassaemia

MCV 75-96 Reduced Very Reduced

Mean Corpuscular Hb

27-23 Reduced Very Reduced

Mean Corpuscular Hb Conc.

32 -35 Reduced Normal

Fetal HB (HbF) <2% Normal Raised

HbA2 2-3% Normal Raised

Red cell width high normal

THALASSAEMIA If mother has Thalassaemia Trait ,

husband should be investigated for Trait .If both partners are positive for trait , prenatal diagnosis for foetal is indicated .

There is 1: 4 chances of fetus being Thallassaemia major .

Therapeutic termination of pregnancy is indicted in such situation .

If foetus is has normal Hb Or Trait only Pregnancy can be continued and mange the anaemia by blood transfusion as per need.

SICKLE CELL HAEMOGLOBINOPATHY

O.1- 1.0 % in west African and American blacks .

RBC have abnormal HB called HbS, having faulty Beta chains in Hb, results from a single Beta chain substitution of glutamic acid by Valine at colon 6 of Beta globin chain .

When HbS is exposed to low O2 tension ,Hb precipitates in long crystals , cell become elongated and sickle shape . Red cell membrane changes make these abnormal shaped cells more fragile –life spine reduces resulting in anaemia .

SICKLE CELL HAEMOGLOBINOPATHY It may have serious implications in pregnancy

and women may develop Sickle cell crisis. Patient frequently experience vicious circulation

events as progressive low O2 tension develops. Sickle cell crisis is an emergency with infarction

in various organs due to sequestration of sickle cells , causing severe pain more so in long bones.

It can happen any time in pregnancy , labour and puerperium .

Low Po2 in general anaesthesia can worsen the crisis

Treatment is by Iv hydration , O2 administration and PCV transfusion.

Prenatal diagnosis is indicate in sickle cell Trait women with sickle cell trait husband , with advice of MTP of an affected pregnancy

HEMOLYTIC ANAEMIA Different types abnormalities in RBC

( acquired or hereditary) Make the cells more fragile , hence rupture more easily and frequently as they pass through capillary circulation specially through spleen .

RBC destruction is faster then their production leading to chronic anaemia.

Patient also develops pre hepatic (hemolytic) Jaundice .

Anaemia and Jaundice put a combined burden over the pregnant women and hence they carry high maternal as well as fetal morbidity and mortality.

SPHEROCYTOSIS RBC are small and sphere shaped ,

rather then being biconcave disc.

There cell membrane is also fragile .

RBC destruction is faster then their production.

Haemolytic anaemia develop.

APLASTIC ANAEMIA Bone marrow aplasia / hypoplasia

means arrest of production of all blood elements like RBC, WBC and platelets

PBF shows Pancytopenia . It can develop following bone marrow

function depression by radiations , chemotherapy , industrial chemicals , drugs and viral infections .

Repeated Whole blood transfusion , prednisolon , erythropoietin , nutrients , bone marrow transplantation Pluripotent stem cell therapy is indicated.

KEY POINTS Anaemias specially nutritional deficiency , are very

common in pregnancy and are major health problem , being more common in developing countries .

Most significant cause (direct & indirect ) of maternal and perinatal mortality and morbidity.

Iron deficiency anaemia continues to be the commonest anaemia during pregnancy , owing to poor dietary habits , can be treated by oral or parenteral iron therapy .

Folic acid deficiency anaemia is associated with fetal neural tube defects can be easily prevented by folic acid supplementation

Thalassaemia and sickle cell anaemia are seen in certain geographic areas , and are associated with significant morbidity