Anemia in pregnancy , definition , causes , pathogenesis, management.

Anemia in pregnancy

1. Anemia in Pregnancy Suhani (135) Sukhman(136) Tanishq(137) Tanvi(138)

2. Definition of Anaemia in pregnancy According to WHO, anemia in pregnancy is present when the hemoglobin concentration in the peripheral blood is 11 g/100 mL or less or (hematocrit <33%). With this criteria 50% of pregnant women are anemic. The Centre for disease control and prevention ( CDC) defines anemia as the Hb concentration of <11gm/dl ( hematocrit <33%) in the first or third trimester or a Hb concentration of <10.5 gm/dl ( hematocrit < 32%) in the second trimester

3. CLASSIFICATION Physiological Anemia of Pregnancy Pathological Anemia Based on etiology

4. Pathological Anemia :- Deficiency Anemia (isolated or combined) Iron deficiency anemia(95%) Folic acid deficiency Vitamin B12 deficiency Protein deficiency Haemorrhagic ACUTE:-following bleeding in early months or APH CHRONIC:-Hookworm infestation,bleeding piles Hereditary (haemoglobinopathies) Thalassemias Sickle cell & other haemoglobinopathies Hereditary haemolytic anemias(RBC membrane defects,spherocytosis) Bone marrow insufficiency hypoplasia or aplasia due to radiation,drugs such as aspirin,indomethacin Anemia of infection Malaria,Tuberculosis,Kala-azar Chronic disease Renal or neoplasm Haematological malignancy Leukaemias,lymphomas Haemolytic SLE,HELLP syndrome,autoimmune haemolysis,drug induced G6PD deficiency

5. B)Based on morphology (3) Normocytic normochromic MCV:-normal MCHC:-normal (1) Microcytic hypochromic MCV:- reduced MCHC:-reduced (2) Macrocytic normochromic MCV:-raised MCHC:-normal Causes:-Vit B12 & Folate deficiency Causes:- T halassemia A nemia of Chronic disease I ron Deficiency anemia L ead poisoning S ideroblastic anemia Causes:- S ickle cell anemia H ereditary spherocytosis A utoimmune haemolytic anemia A nemia of inflammation R enal failure E nzyme deficiency

6. Red Cell Indices:- Mean corpuscular volume (MCV):- It is the measure of average volume of RBCs Normal range:-75-100 femtoliter(fL) Calculated as:- PCV in L/L / RBC count/L Mean corpuscular Hemoglobin (MCH):- It is a measurement of the average weight of hemoglobin in individual erythrocyte Normal range:- 26- 31 picogram (pg) Calculated as:- Hb/L / RBC count/L

7. Mean corpuscular hemoglobin concentration (MCHC):- It is the average concentration of hemoglobin in erythrocytes Normal range:-30-36% Calculated as:- Hb/dL / PCV in L/L Red cell distribution width (RDW):- It is a measure of variability of erythrocyte size

8. PHYSIOLOGICAL ANEMIA IN PREGNANCY HEMODILUTION: Plasma volume increases by 40-50% Rbc volume increases by 20-30% Liquid component > solid component Decrease in Hb concentration will be maximum around 2nd trimester The anemia is normocytic and normochromic in type.

9. FACTORS RESPONSIBLE FOR ANEMIA DURING PREGNANCY Increased demands of iron Diminished intake of iron Diminished absorption Infection Excess demand 1)multiple pregnancy. 2) women with rapidly recurring pregnancy

10. CLINICAL FEATURES SYMPTOMS : Easy fatigue or weakness Anorexia and indigestion Palpitations Dyspnea Giddiness Swelling of the legs SIGNS: Pallor of varying degree Evidence of glossitis and stomatitis and angular cheilitis Nails become brittle, fragile Koilonychias( spoon shaped nails) Oedema of legs( hypoproteinemia or pre eclampsia ) A soft systolic murmur may be heard in the mitral area due to physiological mitral incompetence.

11. INVESTIGATIONS :- objectives of investigation are to ascertain: Degree of anemia This requires haematological examination which includes estimation of:- Haemoglobin Total Red cell count Packed cell volume Type of anemia 1)Peripheral Blood Smear 2)Haematological Indices Cause of anemia Appropriate investigations based on history and clinical examination are done example:- 1)Stool examination(in case of helminthic infestation) 2)Urine examination (for proteins,sugar & pus cells)

12. Peripheral blood smear:- Pencil cells Target cells Microcytosis Hypochromasia

13. Haematological indices:- Hb <10gm% Rbc< 4 million per cubic mm PCV<30% MCHC<30% ( most sensitive index of IDA) ( normal value is 32-36%) MCV<75 fL ( normal MCV in pregnancy is 75-100 fL) MCH<25 pg ( normal value is 27-31 pg) IRON PROFILE:- TIBC is raised ( > 400 mg /dL) Serum ferritin <10 microgram /L ( normal value 22-100 microgram /L) Transferrin saturation ( serum iron / TIBC) ( <10%) ( normal value 25-50%) Serum iron < 30 microgram/ 100 ml ( normal value is 60-70 microgram/ 100 ml)

14. HEPCIDIN Liver peptide Regulates iron haemostasis Inhibits iron absorption in SI and iron release from macrophages Helps to differentiate IDA from anemia of chronic disease Value decreased in IDA Increased in anemia of chronic disease

15. MICROCYTIC  ANEMIAS ● DIFFERENTIAL DIAGNOSIS: "TICS“ ● I: Iron deficiency anemia ● C: Anemia of chronic disease ● S: Sideroblastic anemias ● T: The thalassemia syndromes

16. COMPLICATIONS OF ANEMIA IN PREGNANCY: During pregnancy Preeclampsia Intercurrent infection Heart failure Preterm labou r During labour Uterine inertia PPH Cardiac failure Shock Effects on baby Low birth weight Intrauterine death Puerperium Puerperal sepsis Subinvolution Puerperal venous thrombosis Poor lactation Pulmonary embolism

17. IRON DEMAND IN PREGNANCY Total iron requirement during pregnancy is 1000 mg. Rbc volume increase by 450 mL during pregnancy 1 mL rbc needs 1.1 mg iron . Amount of iron needed by maternal rbc is 450x1.1= 500 mg Amount of iron required by fetus is 300 mg Amount of iron lost by urine, stool, sweat is 250 mg Average daily requirement of iron during pregnancy is 4-6 mg Fetus gets iron from mother by active transport. IRON DEMANDS Only 10% of dietary iron is absorbed To achieve the daily requirement of 4-6 mg in pregnancy, a pregnant woman will have to take 40-60 mg of dietary iron. Disadvantage : Practical difficulty Iron supplementation is mandatory in pregnancy

18. TREATMENT PROPHYLACTIC: Spacing of birth- a minimum interval between pregnancies, should be atleast 2 years. Supplemental iron therapy- daily administration of 60 mg of elemental iron along with 1 mg folic acid is a quit effective prophylactic procedure. Tea should be avoided within 1 hr of taking iron tablet. Dietary prescription - a realistic balanced diet, rich in iron and protein should be prescribed Treatment should be instituted to eradicate hookworm infestation, malaria, dysentery, bleeding piles and UTI. Iron and calcium tablets should not be taken together. There should be a minimum gap of 2 hrs.

19. IRON THERAPY Preparations available are : Ferrous fumarate Ferrous gluconate Ferrous sulfate ( widely used) 2 tablet per day throughout pregnancy 180 days after delivery( to replenish iron stores) Hb starts to increase 3 wks later at a rate of 0.7 gm/ dL per week. Hence, Hb levels can be checked every month ( because of marginal rise in value every week) Reticulocyte count is a better marker than Hb( increase within 7 days, max by 10 days) If Hb increase is < 1 gm % after 1 month : inadequate response( most common cause non compliance, defective absorption due to associated GI disorder, pt fails to take iron, concurrent blood loss as in hookworm infestation or bleeding piles, coexistence folate deficiency ) ALTERNATIVE OPTIONS IN NON COMPLIANT PATIENT: Change the salt of iron from ferrous sulfate to ferrous fumarate in affordable patients Unaffordable pt: parenteral therapy SIDE EFFECTS OF ORAL IRON THERAPY: Gastric irritation , Constipation, diarrhoea, nausea, vomiting, epigastric pain, metallic taste. ORAL THERAPY

20. ALTERNATIVE OPTIONS IN NON COMPLIANT PATIENT: Change the salt of iron from ferrous sulfate to ferrous fumarate in affordable patients Unaffordable pt: parenteral therapy SIDE EFFECTS OF ORAL IRON THERAPY: Gastric irritation , Constipation, diarrhoea, nausea, vomiting, epigastric pain, metallic taste.

21. ENHANCERS OF ABSORPTION Haem iron Proteins Ascorbic acid Gastric acidity Low iron stores Increased erythropoietic activity ( high altitude, bleeding, hemolysis) INHIBITORS OF IRON ABSORPTION Phytates Calcium Tannins Tea and coffee

22. PARENTERAL THERAPY INDICATIONS: 1) non compliant pt 2) non tolerant pt , not cooperative( gastritis, nausea , vomiting with oral iron) 3) cases seen for the first time during the last 8-10 was with severe anemia Parenteral therapy can be given through I.V. route or I.M route PARENTERAL IRON APPROVED BY GOVT OF INDIA: 1) iron dextran 2) iron sucrose( most commonly used; it is safe, effective and has less side effects) 3) ferric carboxylate maltose CONTRAINDICATIONS : - first trimester - hemochromatosis - thalessimia major

23. ESTIMATION OF TOTAL IRON REQUIREMENT USING GANZONI FORMULA: Total dose of iron required( mg) = body weight in kg( pre pregnancy weight) x [target Hb - actual Hb gm/L] x 2.4 + 500 mg ( additional to replenish the stores) Iron sucrose Max single dose 200 mg Max iron sucrose/ week 600 mg ( 3 times/ week) 1 vial contains 5 ml/100 mg iron sucrose (1ml = 20 mg of iron sucrose) Rate of iv infusion= 2 vials (200 mg diluted with 100 ml of normal saline) over 30 min

24. BLOOD TRANSFUSION INDICATIONS : Thalassemia major Anemia leading to heart failure Acute haemorrhage leading to severe anemia Hb< 5 gm/dL at any gestational age Hb<5-6.9 gm/dL at more than 34 wks of gestation Bone marrow failure 1 packed cell transfusion per day is given. The quantity should be between 80 and 100 mL at a time.

25. ANEMIA MUKT BHARAT 6*6*6 STRATEGY 6 beneficiaries: -Children 6-59 months of age -Children 5-9 yrs of age -Adolescent girls and boys(10-19 yrs) -Women of reproductive age (20-24 yrs of age) -Pregnant women -Lactating mothers(of 0-6 months child)

26. 6 Institutional mechanisms: -National anaemia mukt Bharat unit -Intra ministerial coordination -Strengthening supply chain and logistics -Convergence with other ministries -National centre of excellence and Advanced research on anaemia control -Anaemia mukt Bharat dashboard and digital portal - one stop shop for anaemia

27. 6 interventions: 1) Prophylactic iron folic acid supplementation

28. 2) Deworming : albendazole -in non pregnant 400 mg twice a year -In pregnant 400 mg after 1st trimester 3) Intensified year round behaviour change communication campaign including ensuring delayed cord clamping 4) Testing of anaemia using digital methods and treatment of anaemia 5) Addressing non nutritional causes of anaemia 6)Mandatory provision of iron folic acid fortified food in public health programmes

29. MEGALOBLASTIC ANAEMIA In megaloblastic anemia there is derangement in the red cell maturation with the production in the bone marrow of abnormal precursors known as megaloblasts due to impaired DNA synthesis. Thus , it maybe regarded as a deficiency disease caused by lack of either VITAMIN B12 or FOLATE or BOTH. In pregnancy, folate deficiency is common compared to vitamin B12. The daily requirement of vitamin B12 in non pregnant condition is 2 mg and during pregnancy is 3 micro gram.

30. CAUSES OF VITAMIN B12 DEFICIENCY: Strict vegetarian diet Gastritis Gastrectomy Crohn’s disease Drugs( metformin, PPIs) MEGALOBLASTIC anaemia of malabsorption syndrome

31. CAUSES OF FOLIC ACID DEFICIENCY: INADEQUATE INTAKE - nausea, vomiting - dietary insufficiency INCREASED DEMAND DUE TO - increased maternal tissue including red cell volume - growing foetus - multiple pregnancy ( daily requirement of folic acid in non pregnant women is 50-100 micro gm/ day and during pregnancy is increased to 400 microgram / day) DIMINISHED ABSORPTION - intestinal malabsorption syndrome is responsible ABNORMAL DEMAND - infection - hemorrhagic states such as peptic ulcer, hookworm infestation

32. CLINICAL FEATURES: Symptoms - Onset is insidious Anorexia Occasional diarrhoea Constitutional symptoms like unexplained fever is often associated. ON EXAMINATION- Pallor of varying degree. Ulceration in the mouth ( glossitis) and tongue. Enlarged liver and spleen. Features of pre eclampsia may be present Haemorrhagic patches under the skin and conjunctiva.

33. Haematological examination and other blood values: Hb level is usually below 10 gm% Hypersegmentation of neutrophils, macrocytosis ,anisocytosis, megaloblast, Howell jolly bodies. MCV, MCH is high but MCHC is normal. TIBC is low . Red cell folate is below 3 ng/ mL( normal non pregnant level being 2.8- 8ng/mL) Serum vit B12 level is below 90 pg /mL ( normal values 300 pg / mL) Serum bilirubin may be raised. Bone marrow shows megaloblastic erythropoiesis .

34. THERAPY: PROPHYLACTIC: All women of reproductive age should be given 400 microgram of folic acid daily. Additional amount (5mg) should be given in situations where demand is high like multiple pregnancy, pt having anticonvulsant therapy, hemoglobinopathies, associated chronic infections or diseases CURATIVE: S pecific therapy includes daily administration of folic acid 5mg orally which should be continued for at least 4wks following delivery. Supplementation of 1mg of folic acid daily along with iron and nutritious diet can improve pregnancy induced megaloblastic anemia by 7-10 days.

35. SICKLE CELL HAEMOGLOBINOPATHIES These are hereditary disorders caused by a point mutation in the beta globin gene on chromosome 11. This results in the substitution of valine for glutamic acid at position 6 of the beta chain of normal Haemoglobin. EFFECTS ON PREGNANCY: -There is increased incidence of miscarriage (25%), prematurity, IUGR and still birth(8-10%). - incidence of pre eclampsia, post partum haemorrhage and infection is increased.

36. MANAGEMENT DURING DELIVERY Prophylactically folic acid 5 mg should be given daily Careful antenatal supervision Penicillin prophylaxis is given to all patients as they are at risk of infection LABOR AND DELIVERY Vaginal delivery is preferred Continuous oxygen therapy by nasal cannula Epidural anaesthesia is preferred Adequate fluid infusion to avoid dehydration and acidosis

37. THALASSEMIA The thalassemia syndromes are the commonly found genetic disorders of blood. The basic defect is reduced rate of globin chain synthesis. As a result, the red cells being formed with an inadequate Hb content. There is deficient erythropoeisis , reduced rbc life span, haemolysis and ultimately anaemia. T he major syndromes are of 2 groups Alpha thalassemia Beta thalassemia Alpha peptide chain production is controlled by 4 genes, located on chromosome 16 Beta chain production is directed by 2 genes, one on each copy chromosome 11 TYPES : - 1) beta thalassemia major 2) beta thalassemia minor

38. CLASSIFICATION OF THALASSAEMIAS TYPE Hb ELECTROPHORESIS GENOTYPE CLINICAL SYNDROME ALPHA THALASSEMIA Hydrops fetalis Hb Barts( 4 gamma chains) Hb H ( 4 beta chains) Deletion of 4 alpha genes Fetal in utero or in early infancy 2) Hb- H disease Hb H ( 4 beta chains) Deletion of 3 alpha genes Hemolytic anemia 3) Alpha Thalassemia trait Normal Deletion of 2 alpha genes It often goes unrecognized and pregnancy is well tolerated. 4)Silent carrier Normal Deletion of 1 alpha gene No clinical or laboratory abnormalities. BETA THALASSEMIAS 1)Beta Thalassemia major Hb F Mutation in both the beta genes Progressive hepatosplenomegaly, impaired growth, anemia, congestive cardiac failure 2) Beta Thalassemia minor Hb A2 Mutation in either of the genes Usually asymptomatic

39. MANAGEMENT INVESTIGATIONS Low MCV and MCH but normal MCHC Serum iron and total iron binding capacity are normal or elevated Serum bilirubin may be raised to about 2-3 mg% Usually anemia is mild TREATMENT These women need careful monitoring for cardiac, liver, thyroid and parathyroid functions. Chelating therapy during pregnancy is safer after 20 wks with desferroxamine. Oral iron therapy in Thalassemia minor is given only when the lab diagnosis of iron deficiency is established In Thalassemia major oral and iv iron therapy is contraindicated.

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