IRON DEFICIENCY ANEMIADr. Diah Ari Safitri, SpPD

ANEMIA - DEFINITION

REDUCTION OF HEMOGLOBIN CONCENTRATION BELOW REFERENCE VALUE

BLOOD PARAMETERS

Hemoglobin concentration (Hb)○F: 7,2 –10; M: 7,8-11,3 mmol Fe/l (12-18 g/dl)

Erythrocytes count (RBC)○F: 4-5,5; M: 4,5-6 x1012/l (4-6 x106 /μl)

Hematocrit (Hct)○F: 37-47; M: 40-54; (37-54%)

Platelet count (Plt)○150 – 450 x 103/μl (150-450 x 109/l)

Leukocytes count (WBC)○4-10 x 109/l (4-10 x 103/ μl)

Erythrocytes parameters Mean corpuscular volume (MCV)

N: 80-100 fl RDW(Red cell Distribution Width) ○RDW = (Standard deviation ÷ mean cell volume) x 100 A

high RDW indicates that the red blood cells are more variable in volume than normal.

Mean corpuscular hemoglobin (MCH) N: 27-34 pg

Mean corpuscular hemoglobin concentration (MCHC) N: 310 – 370 g/lRBC (31-37 g/dl)

Reticulocytes

RET: 0,5-2% ARC (absolute reticulocyte count) : 25-75x 109/l CRC (corrected reticulocyte count) RPI (reticulocyte production index)

RETIC COUNT X (HB OBSERVED/HB NORMAL) X 0.5

Reticulocyte index (RI) RETIC INDEX= RETIC COUNT X HMT OBSERVED/HMT

NORMAL

RI 1.0% -2.0%○healthy individual.

RI < 1% with anemia ○indicates decreased production of reticulocytes

and therefore red blood cells. RI > 2% with anemia ○indicates loss of red blood cells (destruction,

bleeding, etc.) leading to increased compensatory production of reticulocytes to replace the lost red blood cells

DIETARY SOURCES OF IRONDIETARY SOURCES OF IRON

Inorganic Iron eg lentils Organic iron eg beef

DAILY IRON REQUIREMENT 10-15mg/day

(5-10% absorbed)

IRON DEFICIENCY ANEMIA

IRON METABOLISM ABSORPTION IN DUODENUM TRANSFERRIN TRANSPORTS IRON TO THE CELLS FERRITIN AND HEMOSYDERIN STORE IRON

10% of daily iron is absorbed

Most body iron is present in hemoglobin in circulating red cells

The macrophages of the reticuloendotelial system store iron released from hemoglobin as ferritin and hemosiderin

Small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily)

BODY IRON CYCLING BODY IRON CYCLING

IRON METABOLISM

Iron concentration (Fe)○N: 50-150 μg/dl

Total Iron Binding Capacity○N: 250-450 μg/dl

Transferrin saturation Transferrin receptor concentration Ferritin concentration

○N: 50-300 μg/l

IRON DEFICIENCY ANEMIA

ETIOLOGY:○CHRONIC BLEEDING

- MENORRHAGIA - PEPTIC ULCER- STOMACH CANCER- ULCERATIVE COLITIS- INTESTINAL CANCER- HAEMORRHOIDS

○DECREASED IRON INTAKE○INCREASED IRON REQUIRMENT (JUVENILE

AGE, PREGNANCY, LACTATION)

IRON DEFICENCY - STAGESPrelatent

reduction in iron stores without reduced serum iron levelsHb (N), MCV (N), iron absorption (↑), transferin saturation (N), serum ferritin (↓), marrow iron (↓)

Latentiron stores are exhausted, but the blood hemoglobin level remains normal

Hb (N), MCV (N), TIBC (↑), serum ferritin (↓), transferrin saturation (↓), marrow iron (absent)

Iron deficiency anemiablood hemoglobin concentration falls below the lower limit of normal

Hb (↓), MCV (↓), TIBC (↑), serum ferritin (↓), transferrin saturation (↓), marrow iron (absent)

BONE MARROW FILM STAINED FOR BONE MARROW FILM STAINED FOR HAEMOSIDERINHAEMOSIDERIN

DIFFERENTIAL DIAGNOSIS: IRON DEFICIENCY ANAEDIFFERENTIAL DIAGNOSIS: IRON DEFICIENCY ANAEMIA

IRON DEFICIENCY ANEMIA GENERAL ANEMIA’S SYMPTOMS:

FATIGABILITY DIZZENES HEADACHE SCOTOMAS IRRITABILITY ROARING PALPITATION CHD, CHF

CHARACTERISTICS SYMPTOMS

GLOSSITIS, STOMATITIS DYSPHAGIA ( Plummer-Vinson syndrome)

ATROPHIC GASTRITIS DRY, PALE SKIN SPOON SHAPED NAILS, KOILONYCHIA, BLUE SCLERAE HAIR LOSS PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS AN ICE, CLAY)

SPLENOMEGALY (10%) INCREASED PLATELET COUNT

Koilonychia

  

CHEILITIS

BLOOD AND BONE MARROW SMEAR

BLOOD:microcytosis, hipochromia, anulocytes, anisocytosis

poikilocytosis

BONE MARROWhigh cellularity mild to moderate erythroid hyperplasia (25-35%; N 16 –18%) polychromatic and pyknotic cytoplasm of erythroblasts is

vacuolated and irregular in outline (micronormoblastic erythropoiesis)

absence of stainable iron

Severe microcytic, hypochromic anemia

ManagementHistory and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents)

- CURE ANEMIAHistory and/or physical examination is insufficient (e.g old men, postmenopausal women)

- FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT)

Benzidine test GastroscopyColonoscopyGynaecological examination

ORAL IRON ABSORPTION TEST

1. baseline serum iron level2. 200 - 400 mg of elemental iron orally3. serum iron level 2-4 hours after ingestion

IRON DEFICIENCY ANEMIA CURE

ORAL 200 mg of iron daily 1 hour before meal (e.g. 100

mg twice daily) How long?○14 days + (Hb required level – Hb current level) x 4

half of the dose - 6 – 9 months to restore iron reserve

Absorption ○is enhanced: vit C, meat, orange juice, fish○is inhibited: cereals, tea, milk

IRON DEFICIENCY ANEMIA CURE

PARENTERAL IRON SUBSTITUTION Bad oral iron tolerance (nausea, diarrhoea) Negative oral iron absorption test Necessity of quick management (CHD, CHF) 50 - 100 mg daily I.v only in hospital (risk of anaphilactic shock) I.m in outpatient department iron to be injected (mg) = (15 - Hb/g%/) x body weight

(kg) x 3

WHEN DOES IRON BECOME A WHEN DOES IRON BECOME A PROBLEM?PROBLEM?

Normally 2.5 – 3.5g of iron in the body.

Tissue damage when total body iron is 7 – 15 g

IRON OVERLOADIRON OVERLOAD

CHRONIC TRANSFUSION CHRONIC TRANSFUSION OVERWHELMS IRON BALANCEOVERWHELMS IRON BALANCE

PRBC is the red cells in a single donation or “unit” of blood

EFFECTS OF IRON OVERLOAD

Non-transferrin-bound iron (NTBI) circulates in the plasma

Excess iron promotes the generation of free hydroxyl radicals,

propagators of oxygen-related tissue damage

Liver cirrhosis/ fibrosis/cancer

Insoluble iron complexes are deposited in body tissues and end-organ

toxicity occurs

Diabetes mellitus

Growth failure

Capacity of serum transferrin to bind iron is exceeded

Iron overload

Cardiac failure

InfertilityHSC senescence

(Fenton Reaction)

O2- + H2O2 O2 + OH- + HO

Types of iron preparationsTypes of iron preparations

Oral iron preparations:Oral iron preparations: Why the oral iron is preferred to preferred to the parenteral?

1. Ferrous sulphate: tablets 300 mg/day (60 mg Elemental iron),20-20-32% iron, 32% iron, Most irritant& Highest bioavailability.

2. Ferrous sulphate syrup 12 mg/5 ml & ped. Drops 25 mg/ml

3. Ferrous fumarate: 200 mg t.d.s. (65 mg)-33% iron

4. Ferrous fumarate pediatric drops.• Ferrous succinate: 200 mg b.i.d. caps (70 mg) 35% iron• Ferrous gluconate: 600 mg/day b.i..d.. (70 mg) 12% iron• Iron choline citrate solution or tablets: Least irritant,suitable for

children.

1. Sustained-release iron preparations.

2. Formulations containing iron + folate

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Dosage, duration, goal, monitorDosage, duration, goal, monitor

Dose:

A.Treatment: 200 mg elemental /day

B. Prophylaxis: 30 mg elemental iron daily What are your goals?

1. Anemia 2. Stores 3. Cause Dose regimen:

Ferrous sulphate 300 mg increasing gradually to be t.d.s during or after meals for 2 months or till normal Hb level is reached and then for another period to fill the stores (3-6 months)

Duration of treatment is from 3-6 months. Why? How can you monitor your therapy?

RC (1w-3w), HB (1.5 gm/3w), Ferritin, transferrin saturation

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Causes of failure of oral iron

1. Incorrect diagnosis (Chronic disorder, thalassaemia)

2. Non-compliance to oral therapy. Solve?

3. Inadequate iron therapy (Slow-release) Solve?

4. Mal-absorption (What are the causes?)

5.5. DrugsDrugs like tetracyclines, methyldopa, thyroxine, Bisphosphonates, Antacids, H2 blockers.

6. Continuing excessive blood loss. Solve?

7. Concurrent deficiency of other hematinics

8. Superimposed infection or inflammation

9. Underlying uremia (CRF)

10.Malignancy

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Indications of iron therapyIndications of iron therapyMild to moderate anemiaMild to moderate anemia

1.  Prophylactic: • Pregnancy, infancy, children, menstruating women, after partial

gastrectomy

2. Therapeutic: • Nutritional deficiency: ▼Intake or absorption• Anemia of infancy and pregnancy• Anemia due to acute or chronic blood loss (100 ml= 50 mg)

1. Megaloplastic anemia: Treated with Vit. B12 or Folic acid. Why?

2. Astringent: ferric chloride is used in throat paints

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Adverse effects of oral iron= GITAdverse effects of oral iron= GIT

1.1. GIT upsets (15-50%): GIT upsets (15-50%): • Nausea, vomiting, epigastric pain, colicky pain,

hyperacidity & constipation or diarrhea.

2.2. Black staining of teethBlack staining of teeth.

3.3. Black stoolsBlack stools.

4.4. FailureFailure of oral iron therapy 

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Contraindications of iron therapy

1. Hemochromatosis and hemosiderosis.2. Anemia of chronic inflammatory disease, 3. Repeated blood transfusions. Hemolytic anemia 4. Active liver or renal disease5. GIT; enteritis, diverticulitis, colitis, ulcerative

colitis, peptic ulcer

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