Iron defciency anemia and recent advances in management

Iron defciency anemia and recent advances in management - nutrition bleeding IDA occult blood stool

1. Iron defciency anemia and Recent advances in management Chair person:- Dr Seetaram N K Student:- D r M d Juned

2. Anemia is defined as reduction in total circulating red cell mass below normal limit Anemia reduces the oxygen carrying capacity of the blood leading to tissue hypoxia It is absolute when red cell mss decreases and relative when plasma volume increases

3. Causes of anemia

4. Iron metabolism Dietary iron Absorbtion Transport Distribution Storage Physiologic regulation

5. Iron is required by every cell in the body It has vital role in Oxidative metabolism Cellular growth and proliferation O2 transport and storage Iron must be bound to protien Inorganic or ionic form is dangerous

6. Iron exceeds the body capacity – toxicity Too littlte -- metabolic process inhibited

7. Heme is an iron-chelated porphyrin ring that functions as a prosthetic group ( nonamino acid component) of a protein protoporphyrin IX, is composed of a flat tetrapyrrole ring with ferrous iron inserted into the center .

8. Hemoglobin (Hb)

9. IRON REQUIREMENTS Requirements are determined by obligatory physiological losses and the needs imposed by growth. men require only 13 m g/kg/day (~1 mg of iron), menstruating women ~21 m g/kg/day (~1.4 mg). In the last two trimesters of pregnancy, ~80 m g/kg/day (5–6 mg), infants have similar requirements due to their rapid growth.

10. DIETARY IRON There are 2 types of iron in the diet; haem iron and non- haem iron Haem iron is present in Hb containing animal food like meat, liver & spleen Non- haem iron is obtained from cereals, vegetables & beans Milk is a poor source of iron, hence breast-fed babies need iron supplements

11. AVAILABILITY OF DIETARY IRON Foods high in iron (>5 mg/100 g) include organ meats such as liver and heart, brewer’s yeast, wheat germ, egg yolks, oysters, and certain dried beans and fruits; foods low in iron (< 1 mg/100 g) include milk and milk products and most vegetables.

12. Iron absorption Food sources supply: 10 - 25 mg / day Absorbed in the brush border of the upper small intestine Most dietary iron is nonheme form, <5% bioavailability < 10% dietary iron is heme form, >25% bioavailability

13. Iron absorption from food Iron Absorption (% of dose) 5 10 15 20 25 Veal muscle Hemoglobin Fish muscle Veal liver Ferritin Soy beans Wheat Lettuce Corn Black beans Spinach Rice

14. Factors affecting absorbtion Type of iron:- heme iron vs non heme iron Gastric acid:- promote absorbtion by reducing from ferric to ferrous form Reducing agents:- ascorbate , succinate, SH group of amino acid, Fe3+ to Fe2+ Phosphorous diet:- decrease absorbtion Antacids :- decrease

15. Iron with or after food :- decrease Pancreatic secretion:- decrease Iron deficiency:- increase Infections and GI surgeries:- decrease

16. Iron Distribution

17. Role of Hepcidin in Iron metabolism

18. Proteins involved in iron Homeostasis Hepcidin DMT1 Hephaestin Ferroportin1 Tranferrin receptor HFE Transferrin

19. Iron transport Transferrin – plasma iron transporter protein. Carries less than 1% of total body iron Ferritin – intracellular storage of iron Hemosiderin – long term iron storage pool

20. Storage of iron Ferritin multi-subunit protein primarily intracellular some in plasma Hemosiderin insoluble form of ferritin visible microscopically

21. Iron stain of bone marrow Iron Deficient Marrow Prussian Blue Stain Normal Marrow Prussian Blue Stain

22. Causes of iron defeciency

23. Signs and symptyms Pagophagia - craving ice Pica - craving of nonfood substances e.g., dirt, clay, laundry starch Glossitis - smooth tongue Restless Legs angular stomatitis - cracking of corners of mouth Koilonychia - thin, brittle, spoon-shaped fingernails

24. Koilonychia :- lack of iron structural stress during the keratinisation process of nail formation,a difference in the angle of the distal matrix in comparision to the proxymal matrix , a lack of oxygen to the matrix and atrophy of the matrix, all which would affect the shape of the nail plate

25. Marked hypochromasia, microcytosis

26. Tests for Iron Deficiency Peripheral blood smear Red cell indices (MCV, MCH) Serum ferritin Serum iron / transferrin = iron saturation Bone marrow iron stain (Prussian blue)

27. Differential diagnosis

28. CONDITION SERUM IRON TIBC FERRITIN COMMENT Iron deficiency ↓ ↑ ↓ Responsive to iron Chronic inflammation ↓ ↓  Unresponsive to iron Thalassemia major ↑ N N Reticulocytosis and indirect bilirubinemia Lead poisoning N N N Basophilic stippling of RBCs Sideroblastic anemia ↑ N  Ring sideroblasts in marrow

29. MENTZERS INDEX MCV/RBC >13 - S/O IRON DEFICIENCY ANEMIA 11-13 - INDETERMINATE <11 - THALASSEMIA TRAIT

30. Red cell distribution width RDW measures range of variation of red cell volume Normal range is 11.5 to 14.5 % It is measure of anisocytosis Usually elevated in deficiency of Iron, Folate, B12 Usually normal in Hemoglobinopathy

31. Anaemia of Chronic Disease Thyroid diseases Malignancy Collagen Vascular Disease Rheumatoid Arthritis SLE Polymyositis Polyarteritis Nodosa IBD – Ulcerative Colitis – Crohn’s Disease Chronic Infections – HIV, Osteomyelitis – Tuberculosis Renal Failure

32. Iron deficiency in inflammation and CKD Transferrin sats % Ferritin Inflammation <20% <100 CKD <20% <100 ESRD <30% <500

33. Erythropoeitin Subcutaneous administration is preferred because absorption is slower and the amount of drug req It uired is reduced by 20–40 %. Patients are started on doses of 80–120 U/kg of epoetin alfa , given subcutaneously, 3 times/week. The most common side effect of epoetin alfa therapy is aggravation of hypertension, which occurs in 20–30%

34. Refractory Iron Deficiency Anemia Failure to respond to treatment at a dose of at least 100 mg of elemental iron per day after 4 to 6 weeks of therapy Causes H pylori Autoimmune gastritis Celiac disease Hereditary iron-refractory iron deficiency syndrome (IRIDA)

35. treatment Carbonyl iron (elemental), heme -iron polypeptide (extracted from porcine RBC), polysaccharide-iron complex Ascorbic acid increases oral iron absorption but dose is usually not in significant quantity to make a difference Phytates (cereal grains), tannins (tea) and antacid therapy inhibit oral iron absorption

36. The duration of treatment is depends on the rate of recovery of Hb and the desire to create iron stores. Thus , an individual with an Hb of 5 g/ dL may achieve a normal Hb of 15 g/ dL in about 50 days, whereas an individual with an Hb of 10 g/ dL may take only half that time. after 3–4 months of treatment, stores may increase at a rate of not much more than 100 mg/month .

37. Adjuvants to Iron Therapy vitamin C, cobalt, copper, zinc and manganese. Vitamin C may increase the iron absorption Copper is said to mobilise iron from storage, cobalt is claimed to stimulate erythropoietin production .

38. Adverse reactions to oral iron colicky pain, nausea, vomiting, diarrhoea or constipation, and gastric distress in about 6 to 12% of individuals Iron in liquid form:- blackening of teeth;

39. IRON POISONING Most common in children 1–2 g of iron may cause death, Signs and symptoms of severe poisoning may occur within 30 minutes after ingestion or maybe delayed for several hours. They include abdominal pain, diarrhea, or vomiting of brown or bloody stomach contents containing pills. drowsiness , hyperventilation due to acidosis, and cardiovascular collapse.

40. concentration of iron in plasma:- <63 mm (3.5 mg/L), the child is not in immediate danger. However, vomiting should be induced when there is iron in the stomach, x-ray to evaluate the number of radio-opaque pills remaining in the small bowel . plasma concentration of iron exceeds the total iron-binding capacity >63 mm; 3.5 mg/L), deferoxamine should be administered. Shock , dehydration, and aci

41. Acute Oral Iron Poisoning: (a) Milk and egg yolk mixture is administered to bind the iron. (b) Desferrioxamine 1-2 g IM is administered. (c) Gastric lavage with water containing desferrioxamine is given initially, followed by 5-10g of the same in 100 ml of water being left in the stomach to adsorb any more iron. If desferrioxamine is not available, calcium disodium edetate 35-40 mg/kg may be used .

42. (d)Early replacement of body fluids and electrolytes using isotonic saline, correction of metabolic acidosis and hypotension by using ringer lactate and vasopressor agents, (f) Diazepam to control convulsions

43. In shock:- the drug is administered by IV infusion : 10-15 mg/kg/hour to a maximum of 80 mg/kg in 24 hours. Without shock:- dose of 1-2 g every 3-12 hours; maximum dose 6 g in 24 hours .

44. The average dose for the treatment of iron-deficiency anemia is about 200 mg of iron/day (2–3 mg/kg/day), given in three equal doses of 65 mg. while small children and infants can tolerate relatively large doses of iron (e.g ., 5 mg/kg). The dose used is a compromise between the desired therapeutic action and the adverse effects.

45. For prevention of iron deficiency in pregnant women:- 15–30 mg of iron/d are adequate to meet the 3–6 mg daily requirement of the last 2 trimesters. For treatment of iron-deficiency anemia, a total dose of about 100 mg (35 mg TID) may suffice.

46. Indications for iv iron Severe symptomatic anemia requiring accelerated erythropoesis Failure of oral iron from g.i intolerance Failure of oral iron due to absorption issues H pylori infection, autoimmune gastritis, celiac disease, gastric bypass surgery, inflammatory bowel disease Cancer and chemotherapy associated anemia Anemia with chronic renal disease (with or without[?] dialysis dependance ) Heavy ongoing g.i or menstrual blood losses

47. High molecular weight Iron Dextran is not routinely used anymore due to a much poorer safety profile ( anaphalyctoid reactions) in comparison to newer iron preparations Hemoglobin iron deficit (mg) = Body Wt x (14 - Hgb ) x (2.145)+1000

48. parenteral iron Preparations and dosage (i) Iron-dextran: 15 ml vial, 50 mg of elemental iron/ml. (ii) Iron-Sorbitol-Citric acid complex: 1.5 ml vial, 50 mg of iron/ml. For IV use: (i) High molecular weight iron dextran, 1-2 ml vial, 50 mg iron/ml. (ii) Low molecular iron dextran 2ml vial, 50 mg of iron/ml (iii) Iron saccharate (Ferric hydroxide complexed with sucrose), 5ml vial, 20 mg of iron/ml .

49. (iv) Ferric gluconate , 5 ml vial, 12.5 mg iron/ml. (v) ferric carboxymaltose , 15 ml single use vial, 50 mg iron/ml, given as 2 doses separated by at least 7 days. (vi) Ferumoxytol , 17 ml single use vial, 30 mg iron/ml, given as 2 doses separated by 2-8 days .

50. lron -dextran It is a high molecular weight colloidal solution containing 50 mg elemental iron Route:- i.m . as well as i.v. By i.m . route it is absorbed through lymphatics , circulates without binding to transferrin and is engulfed by RE cells where iron dissociates and is made available to the e rythron for haemesynthesis .. dextran is antigenic:- anaphylactic reactions are more common

51. Test dose:- 25mg (0.5ml) gradually over 30secs an observe for 1hr IM: Injectio n is given deeply in the gluteal region using Z track technique Iron dextran can be injected 2 ml daily, or on alternate days, or 5 ml each side on the same day Intravenous: A dose of 2 ml containing 1OO mg iron is injected per day taking IO 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

52. Ferrous-sucrose This newer formulation is a high molecular weight complex of iron hydroxide with sucrose, on i.v. injection is taken up by RE cells, where iron dissociates and is utilized. It is safer than the older iron dextran dose of 100 mg (max 200mg ) can be injected i.v. taking 5 min, once daily to once weekl y till the total calculated

53. Ferric carboxymaltose :- the ferric hydroxide core is stabilized by a carbohydrate shell. It is rapidly taken up by the RE cells, primarily in bone marrow ( upto 80 %), Iiver and spleen . 15ml single use vial 50mg/ml given as 2 dose separated by atleast 7 days or upto I000 mg is diluted with I00 ml saline ( not glucose solution) and in fused i. v. taking 15 min or more. It should not be injected i.m .

54. it has caused a rapid increase in haemoglobin level in anaemia patients and replenished stores. The incidence of acute reaction is very low . Headache, nausea, abdominal pain are generally mild . Hypotension , flushing and chest pain are infrequent . Due to lack o f safety data, it is not recommended for children < 14 years.

55. Lmw Iron Dextran Iron Sucrose Ferric Gluconate Ferumoxytol Ferric Carboxy maltose Administered Dosage 100mg 200 mg 125 mg 510mg 750mg Total Dose Infusion 1000 mg no no 1020 mg 3d apart 1500mg 7d apart Cost Inexpensive Inexpensive Inexpensive Expensive Expensive Indication IDA IDA in CKD IDA in CKD/HD +epo IDA in CKD IDA + IDA in CKD Test dose Yes none none None None Administration Iv (preferred) or im Iv push or 15m infusion i.v push or 1hr infusion 17s i.v push or 15 m infusion 7.5 m iv push or 15 m infusion

56. Response to oral Iron Therapy Peak reticulocyte count 7 - 10 d. Increased Hb and Hct 14 - 21 d. Normal Hb and Hct 2 months Normal iron stores 4 - 5 months

57. References Harrison 20 th edition Clinical laboratory hematology Shirlyn B. McKenzie 2 nd edition Wintrobes clinical hematology 14 th edition Goodman and gilman’s 13 th edition