Anemia in Pregnancy

By Dr. Ashok MosesMedical Advisor Franco-Indian

Pharmaceuticals Ltd.

Anemia in Pregnancy

• Commonest medical disorder.• High incidence in underdeveloped countries.• Increases maternal morbidity and mortality.• Increases peri natal mortality.

Anemia in Pregnancy Definition by WHO.• Hemoglobin less than 11.0 gms/dl or hematocrit

<32.Classification• Mild anemia – 9.0 – 10.9 gms/dl.• Moderate -----7.8 – 9.0 gms/dl.• Severe ------ < 7.0 gms/dl• Very severe ----- < 4.0 gms/dl

ETIOLOGY

• There are 3 main causes :1. Decreased erythrocyte production

(Hypoproliferative anemia)• Iron defficiency• B 12 defficiency• Folate defficiency2. RBC destruction3. RBC Loss*90 % of anemia in pregnancy is due to iron defficiency

Physiological changes in pregnancy

• Plasma volume increases 50% by 34 weeks.• RBC mass increases by only 25%.• Results in hemodilution. i.e reduced Hb,

hematocrit, RBC count.• No change in MCV or MCH.• 2-3 fold increase in Fe requirement.• 10-20 fold increase in folate requirement.

Normal iron metabolism

- The primary function is oxygen transport.

- Iron is absorbed by duodenum and jejunim

- Average total body iron content 3500-4000 mg.

- Approximately 2/3 found in hemoglobin,

- Iron is also stored in RE cells (BM, Spleen and liver) as hemosiderin and ferratin.

- Also iron found in myglobin and myeloperoxidase and in certain electron transfer.

- Iron is more stable in ferric state (Fe+++) than in ferrous state (Fe++).

Iron + Hem

Iron Metabolism

Absorption of Iron

http://youtu.be/umtxr9SQoI8

• Dietary iron:• Iron is present in food as ferric hydroxides (ferric-

protein complexes and hem-protein complexes).• -meat, liver• -vegetables, eggs.• -The average diet contains 10-15mg and only 5-10% is

normally absorbed.

• Iron requirements:• It varies depending on sex and age:• Male/female 0.5-1 mg/day• Pregnant female 1-2 mg/day• Children 0.5 mg/day

Common anemia's in pregnancy

• Common• Nutritional Iron, B12, and Folate defficiency.

• Hemoglobinopathies Thallasemias, Sickle cell anemias.

• Rare causes: Aplastic anemia, Auto immune hemolytic, Leukemia, Hodgkins disease, PNH.

Clinical features:When ID is developing, the RE stores (hemosiderin and ferritin) become completely depleted before anemia occurs.At an early stage, no clinical abnormalities.Later, patient may develops general symptoms and signs of anemia.In severe case of IDA ridged or spoon nails

Effects of anemia in pregnancy

• Mother1. High output cardiac failure.( More likely if

pre-ecclamsia present)2. PPH.3. Predisposition to infection.4. Risk of thrombo embolism.5. Delayed general recovery especially after CS.

Effects on fetus

1. IUGR2. Preterm birth3. LBW4. Depleted Fe store5. Delayed cognitive function

Laboratory findings

Red cell indices:

Low Hb conc.

MCV, MCH, MCHC* Blood film:

Hypochromic microcytic Picture.

Occasional Target cells.

Pencil shaped poikilocytes.

Normal reticulocyte count.

Bone marrow iron:

Normal to hypercellular.

RBC precursors are increased in number.

Iron stain negative.

Chemical testing on serum:

Serum iron Decreased

Transferrin/TIBC Normal to High

Serum ferritin Decreased (Very low)

Hypochromic Microcytic picture (IDA)

--ve BM Iron Stain +ve

• Serum iron decreased (<12 micro mol / l)

• Total iron binding capacity :TIBC in non-pregnant state is 33% saturated with iron .when serum iron level fall ,<15% ofTIBC saturated.by fall in saturation,the TIBC INCREASED.

• S. ferritin :In healthy adults ferritin circulate in plasma in range of 15_300 pg/l. in iron deficiency anemia it is the first test to become abnormal

MANAGEMENT• Objectives: 1- To achieve a normal Hb by end of pregnancy 2- To replenish iron stores• Two ways to correct anaemia: I- Iron supplementation . Oral Fe . Parenteral Fe II- Blood transfurion • Choice of method: It depends on three main factors:

• Severity of the anaemia• Gestational Age.• Presence of additional risk factor

MANAGEMENT

• Recommended supplementation for non-anemic 30 - 60mg /day of elemental iron

• Anemic gravida’s 120 –240mg / per day• If intolerance to iron tablets – enteric coated tablet /

liquid suspension• Supplementation with folic acid + Vit C.• Therapeutic results after 3 weeks – rise in Hb % level

of 0.8gm/dl/ week with good compliance.• Treatment continued in the postpartum period to fill

the stores

Elemental iron

• What is elemental iron? Iron supplements have two different

amounts of iron listed on the same package. The higher number is the total amount of iron in the supplement. The second, smaller number is the amount of elemental iron.

Elemental iron

• Elemental iron is the total amount of iron in the supplement available for absorption by the body. Each type of iron has a different percent of elemental iron. For instance:

• Carbonyl has 100% elemental iron.• Ferrous fumarate has approximately 33% elemental iron.• Ferrous sulfate has 20% elemental iron.• Ferrous gluconate has 12% elemental iron.• Ferric ammonium citrate has 18.5 % elemental iron

( Dexorange).

Elemental iron

• But the ferrous salts have a lower tolerability when compared with the ferric salts due to the high incidence of side effects on the GI Tract with ferrous salts.

• The amount of elemental iron in a supplement is

typically listed in the Supplement Facts panel. In addition, some iron supplements will indicate the total milligrams of elemental iron on the front of the package making it easy for patients to compare different iron supplements.

Elemental iron

• Ferric Ammonium Citrate (Dexorange) is one of the best iron supplements. Ferric Ammonium Citrate provides an optimum tolerance of the iron preparation, which is of utmost importance in maintaining long term patient compliance to any hematinic therapy.

MANAGEMENT

• Severe anaemia: (Hb < 8gm/dl)- preferably parenteral theraphy in the form of I/M or I/V iron

- I/M : ( Iron sorbitol) with “Z” technique - I/V : (iron sucrose)• Iron needed = (Normal Hb – Pt. Hb) x Wt in kg x

2.21+1000)

MANAGEMENT

Dose given I/M or I/V by slow push 100mg / day or the entire dose given in 500 ml N/S slow I/V infusion over 1-6 hours

• Marked increase in reticulocyte count expected in 7-14 d Blood transfusion:• may be required to treat severe anemia near term or when

some other complication such as placenta previa present.• Gross anemia

• Packed red cells transfusion (Under cover of loop diuretic)

• Exchange transfusion (Under cover of loop diuretic)

MANAGEMENT

Side effect of Fe Oral therapy: . G. I upset. . Constipation. . Diarrhoea. (More with ferrous salts).Parentral: - skin discolouration - local abscess - allergic reaction - Fe over load.

MEGALOBLASTIC ANEMIA

• Complicates upto 1% of pregnancies• Characterized by : - RBC with high MCV

- White blood cells with altered morphology (hypersegmented neutrophils).

• Usually caused by : - Folate deficiency may occur after exposure to sulfa drugs or hydroxyurea

- Vitamin B12 deficiency

FOLATE DEFICIENCY ANEMIA

At cellular levelFolic acid reduced to Dihydrofolicacid then Tetrahydro-folicacid . (THF) e 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

at particular risk.

FOLATE DEFICIENCY ANEMIA

Folic acid deficiency more likely if. Woman taking anticonvulsants.. Multiple pregnancy.. Hemolytic anemia; thalasemia

H.spherocytosis Maternal risk: Megaloblastic anemia Fetal risk: Pre-conception deficiency cause neural

tube defect and cleft palate etc.

FOLATE DEFICIENCY ANEMIA

• Diagnosis: Increased MCV ( > 100 fl)• Peripheral smear: - Macrocytosis, hypochromia• - Hypersegmented neutrophils • (> 5 lobes)• - Neutropenia• - Thrombocytopenia

• Low Serum folate level.• Low RBC folate.

FOLATE DEFICIENCY ANEMIA

Daily folate requirement for : Non pregnant women -- 50 -100 microgram Pregnant woman –-------- 300-400 microgram Usually folic acid present in diets like fresh fruits

and vegetables and destroyed by cooking.

Folate deficiency: - 0.5-1.0mg folic acid/day

If F/Hx. of neural tube defect - 4mg folic acid/day

Vitamins B12 Deficiency

It is rareOccurs in patients with gastrectomy , ileitis, illeal resection, pernicious anaemia, intestinal parasites.

Diagnosis:Peripheral smearVitamin B12 level < 80 pico g/ml

Treatment of B12 Deficiency: Vit B12 1mg I/M weekly for 6 weeks.

HEMOGLOBINOPATHIES

• Normal adult Hb. after age of 6 month,• HbA---97%, HbA2---(1.5-3.5%), HbF2--<1%.• 4 Globin chains associated with haem complex.• Hb. A = 2 alpha +2 beta globin chains.• Hb.A2= 2alpha+2 delta globin chains.• Hb.F = 2 alpha+ 2 gamma globin chains.• Hb. synthesis is controlled by genes.• Alpha chains by 4 gene,2 from each parent.• Beta chains by 2 genes ,1 from each parent.

HEMOGLOBINOPATHIES

DEFINITION:• Inherited disorders of haemoglobin.• Defect may be in: - Globin chain synthesis------thallassemia. - Structure of globin chains-sickle cell disease.• Hb.abnormalities may be: - Homozygous = inherited from both parents. (Sufferer of disease) - Hetrozygous = inherited from one parent. (Carrier/trait of disease

THALASSAEMIAS

• The synthesis of globin chain is partially or completely suppressed resulting in reduced Hb. content in red cells,which then have shortened life span.

• TYPES: - Alpha thalassaemia. - Beta thalassaemia: . Major . Minor

Beta thallassemia minor

• Beta Thallassemia trait• Heterozygous inheritance from one parent.• Most frequent encountered variety.• Partial suppression of the Hb. synthesis.• Mild anaemia.Investigations: Hb----around 10 g/dl.• Red cell indices: low MCV. low MCH. normal MCHC.• Diagnostic test: Hb. Electrophoresis

Beta Thallassemia Minor

• Management:• Same as normal woman in pregnancy.• Frequent Hb. Testing.• Iron & folate supplements in usual dose.• Parenteral iron should be avoided. because

of iron overload.• If not responded ---I/M folic acid.• blood transfusion close to time of delivery.

Beta Thallassaemia Major

• Homozygous inheritance from both parents.• Sever anaemia.• Diagnosed in paediatric era.• T/m: is blood transfusion.

ALPHA THALASSAEMIA:• Both heterozygous & homozygous forms exist.• Alpha thallassaemia trait.• HbH disease.• Alpha thallassaemia major.

SICKLE CELL SYNDROME

• Autosomally inherited .• Structural abnormality.• HbS - susceptible to hypoxia, when oxygen

supply is reduced.• Hb precipitates & makes the RBCs rigid & sickle

shaped.• Heterozygous----HbAS.• Homozygous-----HbSS.• Compound heterozygous---HbSC etc.

SICKLE CELL SYNDROME

• Sickling crises frequently occurs in pregnancy, puerperium &in state of hypoxia .

• Increased incidence of abortion and still birth growth restriction, premature birth and intra

partum fetal distress with increased perinatal mortality.

• Sickle cell trait:(carrier state) Does not pose any significance clinically.

SICKLE CELL SYNDROME

• Diagnosis: - Hb. Electrophoresis - Sickledext test is screening test• Management: - No curative Tx. - only symptomatic - Well hydration, effective analgesia, prophylactic antibiotics, O2 inhalation, folic acid, oral iron supplement (I/V iron is C/I), blood transfusion

Management During labour

• Comfortable Position• Adequate analgesia• O2 inhalation• Low threshold of assisted delivery• Avoid ergometrine• Prophylactic antibiotics• Continue iron &folate therapy for 3 mo after

delivery• Appropriate contraceptive advice