ANEMIA IN OBSTETRI

Sulchan Sofoewan Departement of Obstetrics and Gynecology Faculty of Medicine Gadjah Mada University

Pendahuluan
Prevalensi Anemia Dunia (%)
57 46 35.6 19 10

Eropa
WHO, 2000

Amerika

Afrika

As-teng

Total

ANEMIA IN PREGNANCY
Definition: Non pregnant : Hb < 12g/dl Pregnant : Hb < 10g/dl Hb concentr lower in midpregnancy In early and near term : 11g/dl CDC criteria: anemia as less than 11g/dl in the 1st and 3rd trim, and less than 10,5g/dl in the 2nd trim

PHYSIOLOGICAL ANEMIA
Fall in Hb level during pregnancy caused by a relatively greater expansion of plasma volume compared with the increase in Hb mass and red cell volume, called hydremia / hemodlution The disproportion between the rates at which plasma and erythrocyte are added to the maternal circulation during the 2nd trim The long-used term: physiological anemia

HYDREMIA/HEMODILUTION
During 10 weeks of pregnancy to 7 day after delivery: Plasma : 30% Red cells : 18% Hb : 19% Cause: physiological anemia

THE ADVANTAGES OF HYDREMIA

The need of circulation is fulfilled To decrease the function of heart To decrease the peripheral resistency To minimized the iron loss during hemorrhage

THE PREVALENCE OF ANEMIA

Pregnant women Young persons Child schools Under 5 yrs child : 50.9% : 57.1% : 47.2% : 40.5%

Prevelansi
Di US: 5-10% wanita 20 to 44 th menderita defisiensi besi Lebih tinggi, pada kelompok berisiko:
Wanita hamil, apalagi berulang dengan interval pendek Paritas tinggi Soial ekonom dan edukasi rendah Wanita dengan riwayat menoragi Kehamilan ganda Diet rendah daging dan vitamin C Donor darah lebih dari 3 kali per tahun Adolesent Pengguna aspirin

Prevalensi anemia di Indonesia, 1995 (%)

63.5 55.5

35.9

Semua

Wan hamil

Pra sekolah

THE INFLUENCES OF ANEMIA TO THE PREGNANCY, DELIVERY AND PUERPURIUM

To increase the morbidity and mortality of maternal and perinatal

CLASSIFICATION OF ANEMIA
Iron deficiency anemia Megaloblastic anemia Hypoplastic anemia Hemolytic anemia

IRON DEFICIENCY ANEMIA

Iron deficiency anemia: The most common anemia in pregnant women, especially in the 3rd trim Iron metabolisme depend on dynamic equilibrium

DYNAMIC EQUILIBRIUM
Influenced by: Hb destruction Up take of bone marrow for Hb synthesis Utilization / deposition in the tissue Absorption in the intestine

Fisiologi perubahan kadar hemoglobin selama kehamilan

Perubahan fisiologis volume intravaskular Volume plasma meningkat 50-70 %

Mulai minggu ke 6, puncak ke 32, plato sampai persalinan

Sel darah merah meningkat 20-35 %

Mulai minggu ke 12
Kenaikan vol plasma melebihi sel darah merah hemodilusi Ameneorea dan kenaikan absorpsi besi dan folat menaikan cadangan besi Penurunan fisiologis kadar hemoglobin dan hematokrit Anemia: penurunan lebih dari 2 SD

Kebutuhan besi normal

Jumlah besi pada wanita dewasa normal: 2-2,5 gm Kebutuhan besi selama kehamilan: 1000 mg 200 mg dikeluarkan bersama darah saat melahirkan 300 mg untuk janin dan plasenta 500 mg untuk sel darah merah 500 mg hasil metabolisme kenaikan SDM cadangan besi ibu: cadangan minimal 20% wanita dg cad besi > 500 mg 40% antara 100-500 mg dan 40% <100 mg
Kenaikan vol SDM 450 ml 1 ml SDM berisi 1.1 mg element besi 450 ml X 1.1 mg/ml = 500 mg

Dietary iron intake 9 mg, iron requirements 12-18 mg/day, recommended daily allowance 27 mg, tolerable upper intake 45 mg. Absorpsi besi naik dari 0,8 mg pada awal kehamilan sampai 7,5 mg per hari pada akhir kehamilan.

Sumber besi
Jenis besi diet Heme iron (High bioavailability): daging dan jeroan Penghambat absorpsi Kalsium dan mangane yang ada dalam diet seharihari Tanin (teh, kopi dan coklat) Asam fitat (bijibijian, kacangkacangan, beras) Serat, protein kedelai Penguat absorpsi Protein sehari-hari

Nonheme iron (Low bioavailability): daundaunan, produk makanan dan garam yang difortifikasi besi, kacangkacangan, buncis, bayam, lobak, kentang, labu, pisang, strawberi, cherries, melon dll

Protein, asam amino Asam yang mereduksi feri ke fero: asam askorbat (tomat dan jeruk), asam sitrat, malat , laktat dan tartarat Hasil fermentasi: yoghurt

Elemen Besi
Iron Salt Elemental Iron Content 20%
30% 12%

Required to Provide 30 mg of Iron 150 mg

100 mg

Ferrous sulfate
Ferrous sulfate, dry

Ferrous gluconate

250 mg

Diagnosis
Klinis: tanda dan gejala klinis Laboratori
Hemoglobin dan hematokrit turun Mikrositosis dan hipokromia Feritin serum turun (<15 g/L)
Cut off 30 mg: PPV 85%, NPV 90%

Konsentrasi besi turun Serum binding capacity meningkat Sumsum tulang: no stainable iron

Terapi
Tujuan:
1. koreksi hemoglobin dan cadangan besi 2. memperbaiki pregnancy outcome

Sifat: preventif atau kuratif

Preventive: optimasi intake besi & suplementasi rutin besi Kuratif: hanya diberikan pada wanita hamil dengan anemia atau cadangan besi rendah

Women with prepregnancy ferritin levels >20 mg/L did not have a marked decline in serum ferritin throughout the course of pregnancy in contrast to <20 mg/L (Kaufer and Casanueva,1990) Preparat: 30 mg element besi Efek samping: harus diperhatikan

PROT BOUND IRON & TOTAL IRON BINDING CAPACITY

Prot bound iron (BI): 90 120 ug / 100ml Total iron binding capacity (TIBC): 300 360 ug / 100 ml Iron deficiency anemia: BI : decrease TIBC : increase

IRON LOSS DURING DELIVERY

Newborn : 400 mg Placenta : 150 mg Hemorrhage : 200 mg Lactation / day : 1,5 mg Total : 750 mg Hb: 0.245 Fe= 34 mg Fe, Iron loss during delivery 220 g Hb or 39% from Hb level before

CAUSE OF IRON DEF ANEMIA

Decrease iron intake Intestinal absorption disturbence Ancylostomiasis Hemorrhage

TX OF IRON DEF ANEMIA

60 mg Fe + 400 ug folic acid / day is better than: 1. Folic acid only 2. Folic acid + Fe + Zn 30 ug 3. Folic acid + Fe + Zn + 11 micronutrients

THE INFLUENCE OF SUPLEMENTATION

To decrease the prevalence of anemia in 3rd trim To decrease the prevalence of anemia in 3 months after delivery To increase ferritin in newborn The length and Apgar score of the newborn more higher than the placebo

SOLVE THE ANEMIA PROBLEM IN INDONESIA

1950 the focus efforts to the pregnant women 1970 through the UPGK in the primary health care Suplementation of : Fe; Fe + folic acid and promoting of health and nutrition, especially to the women workers

THE RESULTS OF EFFORTS

1996 the prevalence of iron deficiency anemia 63,5% Cause of fail: Incontinuity of intake iron tablets consumption Low animal protein consumption Iron deficiency The low of role of micronutrients

Program Penanggulangan Anemia Ibu Hamil

Program suplementasi zat besi belum berhasil menurunkan anemia Rendahnya kepatuhan minum tablet besi merupakan kendala utama Alasan tidak patuh:
Kebanyakan lupa Efek samping yang tidak disukai

CAUSES OF ANEMIA DURING PREGNANCY

Acquired Iron-def anemia Acute blood loss Inflammation or malignancy Folic acid def/megaloblastic anemia Hemolytic anemia Aplastic/hypoplastic anemia

CAUSES OF ANEMIA DURING PREGNANCY

Hereditary Thalassemias Sickle-cell hemoglobinopathies Other hemoglobinopathies Hereditary hemolytic anemias

EFFECT OF ANEMIA ON PREGNANCY

Increased risk of : Abortion Preterm IUGR Stillbirth Obstetrical hemorrhage Maternal deaths

Efek anemia terhadap ibu

Mudah lelah Kinerja menurun (10% vs 5%) Stres kardiovaskular (hb dan saturasi oksgen rendah) palpitasi, sesak nafas dekompensasi jantung Tidak tolerans thd kehilangan darah shock hemoragik MMR meningkat Kesulitan persalinan: partus lama, partus dengan tindakan Infeksi postpartum meningkat Transfusi meningkat risiko tertular penyakit
Muncul setelah kadar Hb turun di bawah 7-8 g/dL

Efek terhadap janin dan neonatus

Dasar: berkurangnya pasokan oksigen ke rahim, plasenta dan janin Efek: Persalinan preterm, BBLR &JMDR (Evidence: II-b) Ibu hamil dengan defisiensi besi tidak menaikkan risiko kelahiran janin dengan defisiensi besi
Plasenta menyediakan cukup cadangan besi untuk janin Delayed cord cramping (3 menit) menaikkan

IRON-DEFICIENCY ANEMIA
The two most common causes of anemia during pregnancy and the puerperium: iron deficiency and acute blood loss Associated with poor nutritional status Maternal need for iron induced by pregnancy average: 800 mg, about 300 mg for the fetus and placenta and about 500 mg for maternal Hb mass expansion and about 200 mg are shed through the gut, urine and skin This total amount 1.000 mg exceeds the iron stores

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With the rather rapid expansion of blood volume duing second trimester, iron deficiency is often manifested In the third trimester, additional iron is needed to augment maternal Hb and for transport to the fetus.

DIAGNOSIS
Classical morphological evidence of iron deficiency anemia: erythrocyte hypochromia and microcytosis is less prominent in the pregnant woman compared with that in the pregnant woman Initial evaluation of a pregnant woman with moderate anemia should include measuremant of Hb, Hmt and red cell indices, serum iron, ferritin. Serum ferritin <15ug/L confirm iron-deficiency anemia

TREATMENT OF IRON-DEF
The objective of treatment: 1. correction of the deficit in Hb mass 2. restitution of iron stores Tx: orally of ferrous sulfate , fumarate, or gluconat, daily dose about 200 mg element iron If can not take oral iron, parenteral Tx is given. Transfusion only for hypovolemia from blood loss, or an emergency operative procedure must be performed on a severely anemic

Studi tentang Pemberian Besi

Ziaei S, Norrozi M, Faghihzadeh S, Jafarbegloo E: A randomised placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with hemoglobin 13.2 g/dl. BJOG vol 114 (6):684-8, 2007

small-for-gestational-age birth rate and the number of women with hypertension disorder increased significantly in the treated group in 15.7% vs 10.3%, P = 0.035, and 2.7% vs 0,8%, P = 0.05 CONCLUSIONS: Our finding proves that routine iron supplementation in nonanemic women is not rational and may be harmful (Evidence Ia)

Studi tentang Pemberian Besi

Wu Y, Weng L, Wu L (1998):

To study the efficacy of iron supplementation during pregnancy and its influences on the outcome of pregnancy. Preventive (Hb >11 g/dL) and treatment (Hb <11 g/dL Iron suplement can increase the iron storage and effectively improve the iron deficiency during pregnancy, and has no impact on the pregnancy outcomes. The serum-ferritin in the umbilical vein had no

Studi tentang Pemberian Besi

Wu Y, Weng L, Wu L (1998):

To study the efficacy of iron supplementation during pregnancy and its influences on the outcome of pregnancy. Preventive (Hb >11 g/dL) and treatment (Hb <11 g/dL Iron suplement can increase the iron storage and effectively improve the iron deficiency during pregnancy, and has no impact on the pregnancy outcomes. The serum-ferritin in the umbilical vein had no

K Mahomed. Folate supplementation in pregnancy. The Cochrane Database of Systematic Reviews 1997, Issue 3. Art. No.: CD000183. 83 Evidence based of routine folate supplementation
21 studies, comparing placebo or no supplementation increased or maintained serum folate levels & red cell folate reduction in the proportion of women with low haemoglobin level in late pregnancy & megaloblastic erythropoiesis (odds ratio 0.65, 95% confidence interval 0.45 to 0.95). a possible reduction in the incidence of low birthweight have no measurable effect on any other substantive measures of pregnancy outcome. Where there is evidence that megaloblastic anaemia in pregnancy is a common problem, particularly in areas where malarial infection is common for example, routine supplementation may well be justified. Evidence: Ia

LG Cuervo, K Mahomed. Treatments for iron deficiency anaemia in pregnancy. The Cochrane Database of Systematic Reviews 2001, Issue 2. Art. No.: CD003094.
Five trials, involving 1234 women One trial (n=125) , Oral iron treatment a reduction in the number of women with hemoglobins under 11g/dl , mean hemoglobin level 11.3g/dl compared to 10.5 g/dl (cmp to plasebo) There were no data on clinically relevant outcomes 1 trial (n=74), the intravenous (IV) route of administration was associated with an increased risk of venous thrombosis Authors' conclusions This review provides inconclusive evidence on the effects of treating iron deficiency anaemia in pregnancy due to the shortage of good quality trials Evidence: Ia

Pena-Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid for women during pregnancy. Cochrane Database of Systematic Reviews

2006, Issue 3. Art. No.: CD004736 (Evidence Ia)

Forty trials, involving 12706 women, were included in the review The data suggest that daily antenatal iron supplementation increases hemoglobin levels in maternal blood both antenatally and postnatally Women who receive daily antenatal iron supplementation are less likely to have iron deficiency and iron-deficiency anemia at term as defined by current cutoff values. Side-effects and hemoconcentration are more common in women who receive daily iron supplementation vs weekly. Very limited information related to clinical maternal and infant outcomes was available in the included trials.

Reveiz L, Gyte GML, Cuervo LG. Treatments for irondeficiency anaemia in pregnancy. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD003094.
Randomized controlled trials comparing treatments for irondeficiency anemia in pregnancy. 17 trials, involving 2578 women. Oral iron in pregnancy showed a reduction in the incidence of anaemia (one trial, 125 women; relative risk 0.38 No scientific basis to suggest that in otherwise healthy women, the benefits of treatments for mild anemia in pregnancy will outweigh the adverse effects associated with them. No evidence that in women with iron-deficiency anemia in pregnancy, improvement in womens hematological indices translate into clinical improvements for them or their children Treatments are associated with frequent adverse effects such as gastrointestinal disturbances and poor compliance.
Evidence: Ia

FOLIC ACID DEFICIENCY

Megaloblastic anemia/pernicious anemia Megaloblastic anemia may have developed nausea, vomiting and anorexia Folic acid deficiency during prepregnancy and 1st trim is a cause of NTD Daily folic acid requirement is about 400 ug is recommended Tx: 1 mg folic acid and a nutritious and iron

VIT B12 DEFICIENCY

Megaloblastic anemia caused by lack of vit B12 Addisonian pernicious anemia: failure yo absorb vit B12 because of lack of intrinsic factor Following partial or total gastric resection Crohn disease, ileal resection and bacterial overgrowth in the small bowel Decrease of transcobalamin, serum B12-carrier protein

ANEMIA CAUSED BY ACUTE BLOOD LOSS

Early in pregnancy anemia caused by abortion, ectopic pregnancy and hydatiform mole Trim-III of pregnancy and puerperium anemia resulting from hemorrhage, antepartum bleeding: abruptio placentae and placenta previa Early post partum bleeding and late post partum bleeding

ANEMIA ASSOCIATED WITH CHRONIC DISEASE

Chronic disease recognized as characteri: weakness, weight loss and pallor Wide variety of disorders: chronic infection and malignant neoplasms, hypochromic and microcytic erythrocytes Tbc, endocarditis, osteomyelitis, SLE Chronic renal failure, cancer and chemotherapy, HIV are most common

CHRONIC RENAL DISEASE

Chronic renal insufficiency can be accomp by anemia, due to erythrpoietin deficiency During pregnancy , red cell mass is augmented, but less so than normal pregnancy The degree of red cell expansion correspd to the degree of renal impairment Tx: recombinant erythropoietin used for anemia caused by chronic renal insufficien, chronic inflammation and malignancy

ACQUIRED HEMOLYTIC ANEMIA

1. Autoimmune hemolytic anemia: Due to warm-active, cold-active antibody or a combination, classified as primary/idiopathic, Secondary to underlying diseases, or other factors: lymphomas, leukemia, connective-tissue diseases, infections, chronic inflammatory diseases, or drug induced factors Tx: prednison, 1 mg/kg per day

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2. Drug-induced hemolytic anemia: Must be differentiated from other forms of autoimmune hemolytic anemia Hemolysis typically is mild, it resolves upon withdrawing the drug The severity depand on the degree of hemolysis Tx: corticosteroid quesenable efficacy, transfusion for severe anemia Related to a congenital erythrocyte enzimatic defect glucose-6-phosphate dehydrogenase (G6PD) defic

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3. Pregnancy-induced hemolytic anemia: Unexplained hemolytic anemia during pregnancy is a rare, severe hemolysis develop early in pregnancy and resolves within months after delivery Fetus-infant also demonstrated transient hemolysis, immunological cause is suspected Tx: corticosteroid is effective

OTHER ACQUIRED ANEMIAS

Microangiopathic hemolysis: Complicated PE-E: HELLP syndrome Exotoxin of clostridium perfringes or group A-beta-hemolytic streptococcus Gram neg bacterial endotoxin , or liposaccharide especially with severe acute pyelonephritis

INHERITED ERYTHROCYTE DEFECT

Inherited red cell membrane defect or enzyme deficiencies result in destabilizatn of the membrane lipid bilayer Loss of lipid from the erythrocyte membrane, surface area deficiency poorly deformable cells that undergo hemolysis Inherited membrane defect will cause accelerat destruction: hereditary spherocytosis, pyropoikilocytosis, ovalocytosis

RED CELL ENZYME DEFICIENCY

Erythrocyte enzyme are necessary for its anaerobic utilization of glucose Hereditary nonspherocytic anemia G6PD deficiency Pyruvat kinase deficiency, most common enzyme deficiency it is inherited as an autosomal recessive trait Enzyme deficiency are reduced by drugs or infections

APLAST & HYPOPLAST ANEMIA

Dx: anemia with thrombocytipenia, leucopenia, hypocelluler bone marrow Anemia is induced by drugs and other chemicals, infection, irradiation, leukemia and immunological disorders Fanconi anemia and Diamond Blackfan syndrome inherited autosomal recessive Tx: glucocorticoid most are transfusion, severe: bone marrow or stem cell transplantation

HEMOGLOBINOPATHIES
Sickle-cell hemoglobinopathies: 1) Sickle-cell anemia (SS disease),2) Sickle-cell hemoglobin C disease (SC disease), 3)Sickle-cell beta-thalassemia disease (S-beta-thalassema disease) are the most common of sickle-cell hemoglobinopathies, increased matern/perinatal morbidity and mortality, infection, abortion, stillbirth, neonatal death Tx: folic acid and prophylactic transfusion

THALASSEMIA
Alfa-thalassemia: Genetically determined hemoglobinopathiy characterized by impaired production of one or more of the normal globin peptide chain Abnormal synthesis rates may results in ineffective erythropoeisis, hemolysis and anemia 2 major forms alfa-thalassemia and betathalassemia

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Fetus with alfa-thalassemia at 25, 26 and 32 weeks: ascites, hydrops fetalis Alfa-thalassemia minor characteristic by minimal-moderate hypochromic microcytic anemia, tolerate pregnancy quite well Beta-thalassemia: Decrease beta-chain production and excess alfa-chains precipitate to cause cell membrane damage

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Thalassemia major neonate is healthy at birth, but as the hemoglobin F level falls, become severely anemia Beta-thalassemia minor during pregnancy: mother and fetus are satisfactory Prophylactic iron 60 mg, folic acid 1 mg Prenatal Dx: CVS can be carried out at 9 to 13 weeks.

TERIMA KASIH