Iron deficiency anemia Dr . YASSER AL-AHMADI

Definition of Anemia A reduction in the concentration of hemoglobin in the PB below the normal for the age and sex WHO criteria Adult male < 13g/dL Adult female < 12g/dL Pregnant female < 11g/dL

Body Iron Distribution and Storage Duodenum Dietary iron (average, 1 - 2 mg Utilization Utilization per day) Plasma (TIBC) transferrin (3 mg) Bone Muscle marrow (myoglobin) Circulating (300 mg) (300 mg) Storage erythrocytes iron (hemoglobin) (Ferritin) (1,800 mg) Iron absorption in the intestine is controlled by signaling mechanisms The liver removes and stores excess iron Iron is transported in the plasma in a complex with transferrin Iron is utilized by the muscles to generate myoglobin and by the bone marrow to generate hemoglobin for red blood cells Iron released by tissue breakdown is absorbed and recycled by the body Traces (1 to 2 mg) of iron are lost each day by sloughing of mucosal cells, loss of epithelial cells, blood loss, and menstruation Iron can increase through greater intake of dietary iron, increased efficiency of intestinal absorption, and blood transfusion The human body has not evolved a mechanism to clear excess iron Reference Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341:1986-1995. Sloughed mucosal cells Desquamation/Menstruation Other blood loss (average, 1 - 2 mg per day) Liver Reticuloendothelial macrophages (1,000 mg) Iron loss (600 mg)

GI Absorption of Iron

The distribution of body iron Amount of iron Male Female % in average adult (g) (g) of total Hb 2.4 1.7 65 ferritin & hemosiderin 1.0 0.3 30 Myoglobin 0.15 0.12 3.5 Heme enzyme 0.02 0.15 0.5 Transferrin-bound 0.004 0.003 0.1 iron

Estimated daily iron requirements, Units are mg/day 0.5-1 1-2 1.5-3 1.1 1.6-2.6 Adult men Postmenopausal female Menstruating female Pregnant female Children Female (age 12-15)

What is iron-deficiency anemia ? It is the lack of iron in the blood, which is necessary to make hemoglobin.

Causes of IDA Increased iron requirement Inadequate iron intake Growth spurt: infants, adolescence Menstruation Pregnancy Inadequate iron intake Low iron diet Malabsorption Increased iron loss GI tract Menorrhagea Others

Diagnosis of Anemia History Physical Examination Laboratory Investigation

Patient History Symptoms and its duration Dietary habits/Pica Fatigue, muscle weakness, headache, vertigo, syncope, dyspnea, palpitations, indigestion, etc Dietary habits/Pica Blood loss: Melena, Hematochezia, Hemorrhoid, Menstruation(Menorrhagea) Medications Previous record Family history

Physical Examination Skin pallor Pale conjunctiva/Jaundice Smooth tongue/Stomatitis Splenomegaly/Hepatomegaly Koilonychia (Nail spooning) Esophageal Web

Laboratory Investigation First Line Studies - CBC:Hb, Hcrit, Rbc indices, Cell count, Reti count - PB morphology examination - Chemistry(with LDH ) Second Line Studies - Iron/TIBC/Ferritin - Stool occult blood(3 times) - BM study, others

BLOOD AND BONE MARROW SMEAR microcytosis, hipochromia, anulocytes, anisocytosis poikilocytosis BONE MARROW high 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

Serum iron & iron binding capacity Fe TIBC TRANSFERIN SATURATION FERRITIN

Treatment of IDA Correct underlying cause, if present Iron supplementation Oral iron: The best preperation is ferrous sulphate which contains 67mg of iron in each 200mg (anhydrous) tablet and is best given on an empty stomach in doses spaced by at least 6 hours.if side effects occur (e.g.nausea,abd pain ,costipation or diahrea) these can be reduced by giving iron with food or by using a preparation of lower iron content e.g. ferrous gluconate which contains less iron 37mg per 300mg tablet. The hb should rise at the rate of about 2g/dl every 3 weeks.

Parentral iron - Iron –sorbitol-citrate (jectofer) is given as repeated i.m injections whereas ferric hydroxide-sucrose (venofer) is administered by slow i.v inj or infusion. There may be hypersensitivity or anaphylactoid reactions and parentaral iron is therefore only given when it is considered necessary to replenish body iron rapidly (late pregnancy or p.t on hemodialysis and erythropoietin therapy or when oral iron is ineffective (e.g. severe malabsorption ).the hematological response is the same as in oral therapy.

Q & A When do we prescribe iron for pregnant women ? When ferritin < 8 ng/mL Not when ferritin > 12 ng/mL When do we expect normalization of hemoglobin in patients with IDA undergoing iron treatment (if no continued iron loss) ? Usually in 4 – 6 weeks Does intramuscular or intravenous iron restore hemoglobin level faster than oral iron ? No

Helicobacter pylori infection H. pylori infection usually acquired by oral ingestion in childhood Prevalence 20-50% in industrialized countries Prevalence inversely related to socioeconomic conditions May be inadvertently cured by antibiotics treatment for other reasons Causes continuous gastric inflammation in all infected subjects Well characterized at the molecular biochemical and clinical levels. Effect of this genetic polymorphism is highly penetrant when TPMT-deficient patients are treated with std doses of thiopurine. Dr. Barry Marshall, Nobel laureate

Effects of H. pylori infection High acid output Antral gastritis Duodenal ulcer Low acid output Atrophic gastritis Gastric ulcer Gastric cancer MALT lymphoma Well characterized at the molecular biochemical and clinical levels. Effect of this genetic polymorphism is highly penetrant when TPMT-deficient patients are treated with std doses of thiopurine. Rugae are almost completely lacking

H. pylori infection and iron deficiency anemia Epidemiologic studies show H. pylori (+) associated with decreased ferritin levels Well characterized at the molecular biochemical and clinical levels. Effect of this genetic polymorphism is highly penetrant when TPMT-deficient patients are treated with std doses of thiopurine. Herschko, C Best Practice Clin Hemat 2005 18:363

H. pylori infection: Mechanism of iron deficiency Occult GI bleeding Competition for dietary iron - would expect more patients to be iron deficient Effect on gastric secretion High intragastric pH Low gastric juice ascorbic acid Well characterized at the molecular biochemical and clinical levels. Effect of this genetic polymorphism is highly penetrant when TPMT-deficient patients are treated with std doses of thiopurine. Possible cause of iron deficiency in H. pylori2€ection mediated by achlorhydria Annibale, B. et al. Gut 2003; 52:496

Treatment of H. pylori infection: Effect on pH and ascorbic acid Treatment of H. pylori depends on presence of atrophy Well characterized at the molecular biochemical and clinical levels. Effect of this genetic polymorphism is highly penetrant when TPMT-deficient patients are treated with std doses of thiopurine. Annibale, B. et al. Gut 2003; 52:496