Iron deficiency anemia in pregnancy.pptx

iron deficiency anemia in pregnancy and its management

1. ANEMIA IN PREGNANCY (IRON DEFICIENCY ANEMIA) Dr.G.VENKATA RAMANA MBBS DNB HOD FAMILY MEDICINE RDT HOSPITAL BATHALAPALLI

2. ANEMIA IN PREGNANCY DEFINITION Anemia is defined as a reduction in the oxygen transporting capacity of blood, resulting from a decrease in the red cell mass to subnormal levels Hemoglobin level below 10 g/dl at any time during pregnancy is considered anemia in pregnancy (WHO,1993; CDC,1990) Hb level at or below 9 g/dl requires detailed investigations and appropriate treatment CLASSIFICATION Physiological anemia of pregnancy Pathological anemia

3. Normal hematologic changes in pregnancy   Expanded plasma volume (in excess of the increase in red blood cell mass) and resultant physiologic anemia Mild neutrophilia Mild thrombocytopenia Increased procoagulant factors and decreased natural anticoagulants Diminished fibrinolysis

4. Hematologic changes associated with pregnancy Plasma volume Increased 30 to 50 percent Red blood cell mass Increased 20 to 30 percent Hemoglobin concentration Decreased Red cell lifespan Decreased slightly Erythropoietin Increased Mean corpuscular volume Increased slightly Platelet count No change to decreased slightly White blood cell count Increased ( neutrophilia ) Lymphocyte count No change Monocyte count No change

5.   Hematologic changes associated with pregnancy Basophil count No change to decreased slightly Eosinophil count No change to increased slightly Prothrombin time Decreased slightly Bleeding time No change Total protein S antigen, free protein S antigen, protein S activity Decreased Resistance to activated protein C Increased Fibrinogen, factors II, VII, VIII, X, XII, XIII Increased 20 to 200 percent Antithrombin , protein C, factor V, factor IX No change to increased slightly von Willebrand factor Increased Thrombin activatable fibrinolytic inhibitor, PAI-1, PAI-2 Increased D-dimer Increased

6. Dilutional or physiologic anemia In normal pregnancies, greater expansion of plasma volume relative to the increase in RBC mass is associated with a modest decrease in hemoglobin concentration, which is referred to as physiologic or dilutional anemia of pregnancy CRITERIA OF PHYSIOLOGICAL ANEMIA: The lower limit of physiological anemia during the second half of pregnancy should fulfill the following hematological values : Hb - 10 gm % RBC - 3.2 million/mm3 PCV - 32% Peripheral smear showing normal morphology of the RBC with central pallor

7. Classification of Pathological Anemia Underlying Mechanism Blood Loss Increased Red Cell Destruction ( Hemolysis ) Decreased Red Cell Production Morphology Microcytic anemia Normocytic anemia Macrocytic anemia

8. RBC size/ MCV Reticulocyte count Low or normal* Increased Microcytic MCV <80 fL Iron deficiency (late) Anemia of chronic disease/inflammation Sideroblastic anemias Thalassemia Hemolysis Normocytic MCV 80 to 100 fL Bleeding (acute) Iron deficiency (early) Anemia of chronic disease/inflammation Bone marrow suppression (cancer, aplastic anemia, infection) Chronic renal insufficiency Hypothyroidism Hypopituitarism Excess alcohol Copper deficiency/zinc poisoning Bleeding (with bone marrow recovery) Hemolysis Bone marrow recovery ( eg , after infection, vitamin B12 or folate replacement, and/or iron replacement) Macrocytic MCV >100 fL Vitamin B12 or folate deficiency Excess alcohol Myelodysplastic syndrome Liver disease Hypothyroidism HIV infection Medications that interfere with nuclear maturation ( hydroxyurea , methotrexate, some chemotherapy agents) Hemolysis Bone marrow recovery ( eg , after infection, vitamin B12 or folate )  

9. MICROCYTIC ANEMIA Microcytosis is a descriptive term for red blood cell (RBC) size smaller than the normal range ASSESSMENT OF RBC SIZE Automated hematology instrument Measured in femtoliters ( fL ; 10 -15  L) Determined by passing cells one-by-one through a small aperture in an automated instrument that uses light scattering, refraction, or diffraction to estimate size in three dimensions P eripheral blood smear The normal RBC diameter 7 to 8 microns, approximately the size of the nucleus of a small lymphocyte RBCs that have a diameter less than that of the nucleus of a small lymphocyte on a peripheral smear are considered microcytic  

10. CAUSES OF MICROCYTOSIS Iron deficiency Thalassemia Anemia of chronic disease/anemia of inflammation (ACD/AI) Lead poisoning Sideroblastic anemia

11. IRON DEFICIENCY ANEMIA N ormal total body iron mass: 2.5 g for women,3.5 g for men Approximately 80% of functional body iron is present in hemoglobin, with the remainder located in myoglobin and iron-containing enzymes (e.g., catalase, cytochromes) The iron storage pool , consisting of hemosiderin and ferritin-bound iron in the liver, spleen, bone marrow , and skeletal muscle, contains on average 15% to 20 % of total body iron Because serum ferritin is largely derived from this storage pool, the serum ferritin level is a good measure of iron stores Assessment of bone marrow iron is another reliable but more invasive method for estimating iron stores

12. Iron is transported in the plasma bound to the protein transferrin In normal persons, transferrin is about 33% saturated with iron, yielding serum iron levels that average 120 μg / dL in men and 100 μg / dL in women N ormal total iron-binding capacity of serum is 300 to 350 μ g/ dL Iron is lost at a rate of 1 to 2 mg/day through the shedding of mucosal and skin epithelial cells, and this loss must be balanced by the absorption of dietary iron, which is tightly regulated The normal daily Western diet contains 10 to 20 mg of iron Most is found in heme within meat and poultry, with the remainder present as inorganic iron in vegetables About 20% of heme and 1% to 2% of nonheme iron are absorbable ; hence, the average Western diet contains sufficient iron to balance fixed daily losses

13. Schematic showing iron homeostasis Fe circulates bound to transferrin, which receives most Fe from macrophages that phagocytize senescent RBCs and by enterocytes that absorb a minimal amount of dietary iron, to compensate for the amount of iron lost through cell desquamation and blood loss Most Fe is supplied to the bone marrow for RBC production Excess Fe is stored in the liver and macrophages as a reserve

14. Factors influencing the absorption and bioavailability of dietary iron Absorption of heme iron Amount of heme iron, especially in meat Absorption of nonheme iron Factors facilitating iron absorption Acid : by favouring dissolution and reduction of ferric iron Reducing substances : ascorbic acid, amino acids containing SH radical. R educe ferric iron and form absorbable complexes Meat : by increasing HCI secretion and providing haeme iron Factors impeding iron absorption Alkalies (antacids) render iron insoluble,oppose its reduction Phosphates (rich in egg yolk) Phytates (in maize, wheat) Tetracyclines Presence of other foods in the stomach

15. Recommended dietary allowance of iron   Children 9 to 13 years – 8 mg daily Adolescents 14 - 18 years – 11 mg daily for males 15 mg daily for females

16. Causes of Iron deficiency Low intake and poor bioavailability because of predominantly vegetarian diets Chronic blood loss G astrointestinal tract (e.g., peptic ulcers, colon cancer, hemorrhoids, hookworm infestation) F emale genital tract (e.g., menorrhagia, metrorrhagia , endometrial cancer ) Increased demands not met by normal dietary intake occur during pregnancy, infancy ,adolescence and erythropoietin therapy Malabsorption can occur with celiac disease , crohn’s disease or after gastrectomy

17. Regardless of the cause, iron deficiency develops insidiously Iron stores are depleted first , marked by a decline in serum ferritin and the absence of stainable iron in the bone marrow These changes are followed by a decrease in serum iron and a rise in the serum transferrin Ultimately, the capacity to synthesize hemoglobin, myoglobin, and other iron-containing proteins is diminished, leading to microcytic anemia, impaired work and cognitive performance, and even reduced immunocompetence

18. STAGES OF IRON DEFICIENCY

19. CLINICAL FEATURES W eakness, headache, irritability, syncope, and varying degrees of fatigue and exercise intolerance S ymptoms of pica (intense craving for nonfood items) Cognitive function   Iron deficiency can impair cognitive function in adolescents Restless legs syndrome   Dysphagia Glossitis Angular cheilitis koilonychia

20. Pallor in left side (upper photo: conjunctiva, middle: hypoglossal area, and lower: hand) as compared with normal right side

21. KOILONYCHIA ATROPHIC GLOSSITIS

22. Arbitrary grading of pathological anemia is done according to the level of hemoglobin: Mild  between 8 gm % and10 gm % Moderate  less than 8 to 7 gm % Severe  less than 7 gm %

23. Diagnostic criteria Microcytic and hypochromic red cells L ow serum ferritin and iron levels L ow transferrin saturation I ncreased total iron-binding capacity R esponse to iron therapy For unclear reasons, the platelet count often is elevated Erythropoietin levels are elevated, but the marrow response is blunted by the iron deficiency; thus, marrow cellularity usually is only slightly increased

24. Microcytic , hypochromic red blood cells Small (microcytic) red blood cells are shown, many of which have a thin rim of pink hemoglobin ( hypochromia ) Occasional "pencil"-shaped cells are also present A small lymphocyte is shown for size comparison (arrow) Normal red blood cells are similar in size to the nucleus of a small lymphocyte (arrow), and central pallor in normal red blood cells should equal approximately one-third of the cell diameter

25. Serum ferritin   A subnormal level is most often due to iron deficiency or, very rarely, hypothyroidism or vitamin C deficiency A n acute phase reactant , increase independently of iron status in disorders associated with inflammation, infection, liver disease, heart failure, and malignancy  Serum iron Low in iron deficiency as well as in anemia of chronic disease/anemia of inflammation Raised in liver disease and hemolysis S erum iron may be transiently affected by absorption of dietary or pharmacologic iron, it is recommended that the sample be drawn after an overnight fast

26. Serum transferrin   Circulating transport protein for iron It is increased in iron deficiency & decreased in ACD Levels of transferrin are lowered by malnutrition, liver disease, the acute phase response and nephrotic syndrome, but raised by pregnancy and the oral contraceptive pill The transferrin concentration (in mg/ dL ) can be converted to the TIBC (in mcg/ dL ) by multiplying by 1.389 Transferrin saturation   Ratio of serum iron to TIBC: (serum iron  ÷  TIBC  x  100) Normal values are in the range of 25 to 45 percent Lower transferrin saturation In iron deficiency

27. Soluble transferrin receptor ( sTfR )   Derived from cleavage of the membrane transferrin receptor on bone marrow erythroid precursor cells I ron-deficient patients generally have increased levels of sTfR U sed to distinguish storage iron depletion in the presence of an acute phase response or liver disease, when a raised level indicates iron deficiency RBC protoporphyrin C auses of increased red cell protoporphyrin levels are absolute or relative iron deficiency and lead poisoning Normal values are <30 μg / dL of redcells . In iron deficiency, values >100 μg / dL are seen  

28. RBC zinc protoporphyrin In iron deficiency, intestinal zinc absorption increases, and zinc is incorporated into protoporphyrin in developing RBCs Thus, elevated erythrocyte (RBC) zinc protoporphyrin ( eg , >80 mcg/ dL ) is consistent with iron deficiency However, zinc protoporphyrin is not specific for iron deficiency as it may be elevated in inflammatory states, hemodialysis, and lead poisoning Bone marrow iron stain   Staining of the bone marrow aspirate smear for iron provides a qualitative assessment of iron in bone marrow cells ( eg , macrophages, red blood cell precursors ) Stainable bone marrow iron is considered the gold standard for assessing iron stores but is rarely required for diagnosis

29. Investigation of the cause Upper and lower gastrointestinal tract should be investigated by endoscopy or radiological studies E xclusion of coeliac disease by antibody testing at an early stage of investigation of iron deficiency S tool and urine should be examined for parasites

30. Prussian blue staining of bone marrow   Prussian-blue staining of bone marrow Positive iron stores (arrow) seen on left and negative on right

31. Diagnosis of iron deficiency in adults

32. COMPLICATIONS OF ANEMIA IN PREGNANCY During pregnancy: The following complications are likely to increase : ( 1) Preeclampsia ( 2) Intercurrent infection (3 ) Heart failure at 30–32 weeks of pregnancy ( 4) Preterm labor During Labor: ( 1) Uterine inertia (2 ) Postpartum hemorrhage (3 ) Cardiac failure (4 ) Shock PUERPERIUM : There is increased chance of : (1) Puerperal sepsis (2) Subinvolution (3) Poor lactation (4) Puerperal venous thrombosis (5) Pulmonary embolism

33. Risk periods : The risk periods when the patient may even die suddenly are: ( 1) At about 30–32 weeks of pregnancy ( 2) During labor ( 3) Immediately following delivery ( 4) Any time in puerperium especially 7–10 days following delivery due to cardiac failure or pulmonary embolism EFFECTS ON BABY : Amount of iron transferred to the fetus is unaffected even if the mother suffers from iron deficiency anemia. So the neonate does not suffer from anemia at birth ( 1) There is increased incidence of low birth weight babies ( 2) Intrauterine death  due to severe maternal anoxemia The sum effect is increased perinatal loss

34. TREATMENT PROPHYLACTIC Avoidance of frequent child-births : A minimum interval between pregnancies , should be at least 2 years, if not three, to replenish the lost iron during childbirth process and lactation This can be achieved by proper family planning guidance Supplementary iron therapy : Daily administration of 200 mg of ferrous sulfate (containing 60 mg of elemental iron) along with 1 mg folic acid Tea should be avoided within 1 hour of taking iron tablet Dietary prescription: B alanced diet, rich in iron and protein The foods rich in iron are liver, meat, egg, green vegetables, green peas, figs, beans, whole wheat and green plantains , onion stalks, jaggery , etc

35. Iron utensils should preferably be used for cooking and the water used in rice and vegetable cooking should not be discarded Adequate treatment should be instituted to eradicate hookworm infestation, dysentery, malaria, bleeding piles, and urinary tract infection Early detection of falling hemoglobin level is to be made Hemoglobin level should be estimated at the first antenatal visit , at the 30th week and finally at 36th week

36. CURATIVE Choice of therapy depends on: ( 1) Severity of anemia ( 2) Duration of pregnancy (time available before delivery ) ( 3) Associated complicating factors Treatment options Iron therapy : 1. Oral therapy 2. Parenteral therapy Blood transfusion

37. Oral therapy Iron is best absorbed in the ferrous form Preparations: Ferrous sulfate, ferrous gluconate , ferrous fumarate or ferrous succinate Ferrous sulfate is widely used Fersolate tablet contains 325 mg ferrous sulfate which contains 60 mg of elemental iron, trace of copper and manganese Initial dose is one tablet thrice daily 30 minutes before meals If larger dose is necessary (maximum six tablets a day), it should be stepped up gradually in 3–4 days The treatment should be continued till the blood picture becomes normal Thereafter a maintenance dose of one tablet daily is to be continued for at least 100 days following delivery to replenish the iron stores

38. Iron tolerance test Two iron tablets are given to the patient on an empty stomach, and the serum iron is measured serially over the subsequent 2–3 h Normal absorption will result in an increase in the serum iron of at least 100 μg / dL If iron deficiency persists despite adequate treatment, it may be necessary to switch to parenteral iron therapy Response of therapy is evidenced by: ( 1) Sense of well-being ( 2) Increased appetite ( 3) Improved outlook of the patient ( 4) Hematological examination: (a) Rise in hemoglobin level, (b) hematocrit value returning to normal, (c) reticulocytosis within 7–10 days

39. The elemental iron content and not the quantity of iron compound per dose unit should be taken into consideration. Liquid formulations may stain teeth Should be put on the back of tongue and swallowed Side effects : Epigastric pain, heartburn, nausea, vomiting, bloating, staining of teeth, metallic taste, colic, etc. Tolerance to oral iron can be improved by initiating therapy at low dose and gradually escalating to the optimum dose Constipation is more common (believed to be due to astringent action of iron) than diarrhoea (thought to reflect irritant action)

40. Draw backs Intolerance Unpredictable absorption rate Contraindications of oral therapy : ( 1) Intolerance to oral iron (2 ) Severe anemia in advanced pregnancy Considering the unpredictable absorption and utilization following oral therapy, parenteral therapy is the preferred choice

41. Parenteral iron - Indications Indications of parenteral therapy : Contraindications of oral therapy Patient is not cooperative to take oral iron Cases seen for the first time during the last 8–10 weeks with severe anemia Estimation of the total requirement For iron sucrose 2.4 × Pre pregnancy weight (kg) × (Target Hb – patient’s Hb , g/ dL ) + 500 or 1000 mg (for stores ) For iron dextran 0.3 × W (100– Hb %) mg of elemental iron.Where W = patient’s weight in pounds. Hb % = observed hemoglobin concentration in percentage Additional 50% is to be added for partial replenishment of the body store iron

42. IRON DEXTRAN It is a high molecular weight colloidal solution containing 50 mg elemental iron/ml O nly preparation that can be injected i.m . as well as i.v . Intramuscular Injection is given deeply in the gluteal region using Z track technique (to avoid staining of the skin ) Iron dextran can be injected 2 ml daily, or on alternate days, or 5 ml each side on the same day (local pain lasting weeks may occur with the higher dose ) Intravenous After a test dose of 0.5 ml iron dextran injected i.v. over 5–10 min, 2 ml can be injected per day taking 10 min for the injection Alternatively , the total calculated dose is diluted in 500 ml of glucose/saline solution and infused i.v. over 6–8 hours under constant observation Because dextran is antigenic, anaphylactic reactions are more common

43. IRON DEXTRAN Adverse effects Local Pain at site of i.m . injection, pigmentation of skin, sterile abscess-especially in old and debilitated patient Systemic Fever, headache, joint pains, flushing, palpitation, chest pain, dyspnoea , lymph node enlargement An anaphylactoid reaction resulting in vascular collapse and death occurs rarely

44. IRON SUCROSE H igh molecular weight complex of iron hydroxide with sucrose Dose of 100 mg (max 200 mg) can be injected i.v. taking 5 min, once daily to once weekly till the total calculated dose is administered I ncidence of hypersensitivity reaction is very low . P articularly indicated for anaemia in kidney disease patients Oral iron should not be given concurrently and till 5 days after the last injection

45. FERRIC CARBOXYMALTOSE It is administered either as daily 100 mg i.v. injection, or up to 1000 mg is diluted with 100 ml saline (not glucose solution ) and infused i.v. taking 15 min or more Infusion may be repeated after a week It should not be injected i.m I ncidence of acute reaction is very low Pain at injection site, and rashes have occurred, but anaphylaxis is rare Headache, nausea, abdominal pain are generally mild Hypotension , flushing and chest pain are infrequent Due to lack of safety data, it is not recommended for children <14 years

46. IRON ISOMALTOSIDE-1000 Iron bound tightly in a matrix of isomaltosie-1000 S ingle dose of 1- 2 g ( upto 20 mg/kg) i.v. over 15- 30 min Alternatively 100-200 mg i.v. may be injected over 5 min daily Side effects Nausea E pigastric pain Abdominal cramps Constipation or loose motion Serious hypersensitivity reaction is very rare

47. Drug Concentration of elemental iron Dosing (adults) Test dose Premedication Ferric carboxymaltose (FCM) * 50 mg/mL Weight ≥50 kg: 1 or 2 doses of 750 mg, given 7 or more days apart or Weight <50 kg: 1 or 2 doses of 15 mg/kg, given 7 or more days apart Not required .we do not routinely premedicate for any of the IV iron products For patients with asthma or multiple drug allergies, we often give methylprednisolone and a histamine 2 (H2) receptor blocker prior to the iron infusion For patients with inflammatory arthritis, we often give methylprednisolone followed by a brief course of oral prednisone We do not give diphenhydramine as a premedication Ferric derisomaltose (previously called iron isomaltoside) 100 mg/mL Weight ≥50 kg: Single dose of 1000 mg or Weight ≥50 kg: Up to 3 doses of 500 mg given over 7 days or Weight <50 kg: Single dose of 20 mg/kg Not required Ferric gluconate (FG) 12.5 mg/mL Multiple doses of 125 to 250 mg Not required, but recommended if the patient has a history of multiple drug allergies

48. Ferumoxytol ¶ 30 mg/mL Single dose of 1020 mg or 2 doses of 510 mg, given 3 to 8 days apart Not required Iron dextran, low molecular weight (LMW ID) Δ 50 mg/mL Single dose of 1000 mg (diluted in 250 mL normal saline) given over 1 hour or Multiple doses of 100 mg Yes, 25 mg (0.5 mL) prior to the first dose Iron sucrose (IS) 20 mg/mL Multiple doses of 100 to 300 mg Not required, but recommended if the patient has a history of multiple drug allergies .  *  Ferric carboxymaltose can cause hypophosphatemia and should be avoided in individuals with hypophophatemia or at increased risk. Monitoring of serum phosphate is needed in individuals receiving more than one dose ¶ Notify radiologist if patient has a magnetic resonance imaging (MRI) scan, including noncontrast scanning, within 3 months of ferumoxytol administration, as the properties of ferumoxytol affect the appearance of different imaging sequences

49. BLOOD TRANSFUSION Indications To correct anemia due to blood loss and to combat postpartum hemorrhage Patient with severe anemia seen in later months of pregnancy (beyond 36 weeks) Refractory anemia: Anemia not responding to either oral or parenteral therapy in spite of correct typing Associated infection

50. Advantages of blood transfusion (1) Increases oxygen carrying capacity of the blood (2) Hemoglobin from the hemolyzed red cells may be utilized for the formation of new red cells (3) Stimulates erythropoiesis (4) Supplies the natural constituents of blood like proteins, antibodies, etc (5) Improvement is expected after 3 days Drawbacks : (1) Premature labor may start which is more related to blood reaction (2) There is increased chance of cardiac failure with pulmonary edema because of overloading of the heart ( 3) Features of transfusion reaction, if occur, are often exaggerated

51. MANAGEMENT DURING LABOR First stage: The following are the special precautions that are to be taken when an anemic patient goes into labor P atient should be in bed and should lie in a position comfortable to her Arrangements for oxygen inhalation is to be kept ready to increase the oxygenation of the maternal blood and thus diminish the risk of fetal hypoxia Strict asepsis is to be maintained to minimize puerperal infection Second stage : Asepsis is maintained Prophylactic low forceps or vacuum delivery may be done to shorten the duration of second stage Intravenous methergine 0.2 mg should be given soon following the delivery of the baby

52. Third stage: One should be very vigilant during the third stage Significant amount of blood loss should be replenished by fresh packed cell transfusion after taking the usual precautions mentioned earlier The danger of postpartum overloading of the heart should be avoided

53. PUERPERIUM (1) Prophylactic antibiotics are given to prevent infection (2) Predelivery antianemic therapy should be continued till the patient restores her normal clinical and hematological states Even in an otherwise normal case, iron therapy should be continued for at least 3 months following delivery (3) Patient should be warned of the danger of recurrence in subsequent pregnancies