Iron Metabolism and Anemia KARTIKA WIDAYATI TAROENO-HARIADI HEMATOLOGY AND MEDICAL ONCOLOGY CONSULTANT

INTRODUCTION Iron deficiency and iron deficiency anemia become a global health problem and common medical condition Top ranking cause of anemia worldwide and effects on the lives of young children and premenopausal women in both low income and developed countries Iron is crucial for biologic function : Respiration Energy production DNA synthesis Cell proliferation

Human body has evolved to conserve iron : recycling iron and retention no excretion mechanisms Iron absorption is limited to 1-2 mg Most of the iron needed daily (about 25 mg per day) is provided through recycling by macrophages that phagocytose senescent erythrocytes. Hepcidin controls the absorption and recycling Iron deficiency refers to the reduction of iron stores Iron-deficiency anemia is a more severe condition in which low levels of iron are associated with anemia and the presence of microcytic hypochromic red cells. N Engl J Med. 1999;341:1986–95 [18].

Regulation of iron absorption and exportation by enterocytes Transfus Med Hemother 2014;41:213–221

Iron cycle – adaptation mechanisms to iron deficiency Camaschella. N Engl J Med 2015 ; 372;1832-1843

Causes of Iron deficiency Camaschella. N Engl J Med 2015 ; 372;1832-1843

Classification of Iron Deficiency (Anemia) Mechanisms Based on Pathophysiology absolute iron deficiency relative iron deficiency Decreased iron stores Iron deficiency in selected tissue with normal iron stores Based on clinical data iron deficiency iron deficiency anemia Decrease iron stores, without anemia Decrease iron stores with various degree of anemia Based on inheritance genetic IRIDA acquired Constitutive excess of hepcidin production Increased iron demands, decreased intake, blood loss, Reduced absorption Camaschella. Blood Review 2017;31:225-233

Prevalence of anemia, ID and IDA Lancet 2016; 387: 907–16

Interpretation of laboratory investigation L. Percy et al. Best Practice & Research Clinical Obstetrics and Gynaecology 2017 40 55-67

Hemoglobin level to diagnose anemia L. Percy et al. Best Practice & Research Clinical Obstetrics and Gynaecology 2017 40 55-67

Clinical Findings Dry rough skin Damaged hair Cardiac murmur Tachycardia Neurologic dysfunction Angina pectoris vertigo Pallor Weak fatigue Dyspnea Loss of energy headache Painless glossitis Dysphagia Koilonychia alopecia

Diagnosis New Test Bone marrow Perl’s staining Erythrocyte zinc protoporphyrin circulating sTFRC Serum hepcidin Old test low ferritin level <30 ng/ml low serum iron low transferrin saturation < 16% microcytic hypochromic MCV, MCH low increased RDW

TREATMENT algorithm Lancet 2016; 387: 907–16

Treatment Intravenous iron Oral iron sulfat, ferrous gluconas Liposomal iron Treatment should be 6 months

oOral iron supplement preparation Amount (mg) Ferrous iron (mg) Max daily intake (mg elemental iron/day) Ferrous fumarate Ferrous gluconas Ferrous sulphate Ferrous sulphate (dried) 200 300 65 35 60 195 105 180 L. Percy et al. Best Practice & Research Clinical Obstetrics and Gynaecology 2017 40 55-67

Parenteral iron L. Percy et al. Best Practice & Research Clinical Obstetrics and Gynaecology 2017 40 55-67

SUMMARY Clinical history, presentation, and findings include fatigue, pallor, dyspnoea on exertion, and pica. Microcytic, hypochromic anaemia; low reticulocyte count. Characteristics include low serum iron, increased total iron-binding capacity (TIBC), less than 16% transferrin saturation, and low serum ferritin. The diagnosis of iron deficiency anaemia necessitates investigation of the underlying cause. Initial treatment includes oral iron, and intravenous iron as indicated