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Iron Deficiency anemia

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Presentation on theme: "Iron Deficiency anemia"— Presentation transcript:

1 Iron Deficiency anemia
Rakhi Naik, MD, MHS Assistant Professor of Medicine & Oncology, Division of Hematology

2 Disclosures None

3 Objectives Understand the basic physiology of iron absorption, transport and storage Understand the causes of iron deficiency and the compensatory responses seen in clinical lab tests Understand modalities of treatment of iron deficiency and anemia

4 Global Burden of Anemia
Global burden of disease survey KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5


Despite improvements in prevalence rates over the last 2 decades, iron deficiency remains the #1 cause of anemia in the world It accounts for 50% of the global burden of anemia in the world

7 Iron Distribution Adult male has ~4g total body iron stores
Andrews NEJM, 23 DEC 1999 x VOLUME 341, Number 26 5

8 Hemoglobin in RBC Heme is a porphyrin ring containing an iron atom
Each Hgb molecule can bind 4 oxygen molecules at heme site Schechter BLOOD, 15 NOVEMBER 2008 VOLUME 112, NUMBER 10 Schechter BLOOD, 15 NOVEMBER 2008 VOLUME 112, NUMBER 10

9 Iron Absorption Food sources supply: 10 - 25 mg / day
Absorbed in the brush border of the upper small intestine Enhanced by gastric acid Inhibited by tannins, systemic inflammation Most dietary iron is nonheme form, <5% bioavailability < 10% dietary iron is heme form, >25% bioavailability 6 6

10 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 Non-heme iron Heme iron

11 Ferritin – intracellular storage of iron
Transferrin – plasma iron transporter protein. Carries less than 1% of total body iron Ferritin – intracellular storage of iron Hemosiderin – long term iron storage pool Iron must cross two membranes to be transferred across the absorptive epithelium. Each trans membrane transporter is coupled to an enzyme that changes the oxidation state of iron. The apical transporter has been identified as DMT1 (divalent metal transporter 1) . It acts in concert with a type of ferrireductase activity. The basolateral transporter Ferroportin 1 requires hephaestin, a ferroxidase. Iron within enterocytes is stored as ferritin. Transferrin transports from enterocytes and macrophages to the normoblasts in the marrow

12 Iron Storage Ferritin Hemosiderin multi-subunit protein
primarily intracellular some in plasma Hemosiderin insoluble form of ferritin visible microscopically

13 The iron cycle Pietrangelo, NEJM 2004:350:2383
20mg a day of iron is generated every day by destruction of RBC which is then reused for red cell production in the bone marrow Body losses of iron are normally 1-2 mg/day which is made up for by similar amount of iron absorption from the gut. Pietrangelo, NEJM 2004:350:2383

14 Iron Losses Iron is closely conserved in humans
<0.05% of iron is lost per day normally Very small amounts in urine, bile and sweat Cells shed from skin, intestinal and urinary tracts Menstrual blood loss Pregnancy and lactation Humans have NO other physiologic means to excrete excess iron 7 7

15 Pathogenesis of Iron Deficiency
Blood loss Occult or overt GI losses, traumatic or surgical losses Failure to meet increased requirements Rapid growth in infancy and adolescence Menstruation, pregnancy Inadequate iron absorption Diet low in heme iron Gastrointestinal disease or surgery Excessive cow’s milk intake in infants 8 8

16 Andrews NEJM, 23 DEC 1999 x VOLUME 341, Number 26

17 Features of Iron Deficiency Anemia
Depends on the degree and the rate of development of anemia Symptoms common to all anemias: pallor, fatigability, weakness, dizziness, irritability 13 13

18 Other features of IDA 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 14

19 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) 15 15

20 Marked hypochromasia, microcytosis

21 Bone Marrow Circulation Low Hgb High sTfR Iron Deficiency
Reticulocyte Low Hgb High sTfR Erythroblast TfR+ Erythrocyte Iron Deficiency Serum Fe Transferrin Low sFt/Liver Fe Low Serum Fe/TS Macrophage Spleen

22 Sequential Changes in IDA

23 Differential for low serum ferritin
Iron Deficiency

24 CBC in Iron Deficiency Anemia
White blood count normal Hemoglobin < 14 g/dl, Hematocrit < 36% Mean corpuscular volume < 80 fl Mean corpuscular hemoglobin < 26 pg Platelet count normal or high Reticulocyte % low Absolute reticulocyte count generally low

25 Lab values in severe IDA

26 Differential Diagnosis of IDA
Thalassemia trait (low MCV, normal RDW) Imbalance of globin chain production Anemia of inflammation Decreased iron utilization in the face of adequate iron stores Low ferritin / serum transferrin receptor 21 21

27 IDA vs. Inflammation No D Ferritin IDA Inflammation Serum Iron
Transferrin sat sfTR / log Ferr Marrow Iron No D TfR-ferritin index <1.0 suggests the diagnosis of ACD, while an index >2.0 suggests either IDA or the combination of IDA and ACD

28 Punnonen, K, Blood 1997; 89:1052 TfR-ferritin index <1.0 suggests the diagnosis of ACD, while an index >2.0 suggests either IDA or the combination of IDA and ACD

29 Iron stain of bone marrow
Normal Marrow Prussian Blue Stain Iron Deficient Marrow Prussian Blue Stain

30 Treatment Most patients are treated initally with oral iron unless there is an absorptive problem. Dietary sources + FeSo4 BID. TID is very constipating and causes gastric distress; commonest cause for noncompliance Iv iron is no longer ‘dangerous’. The newer formulations such as iron sucrose, lmw iron dextran and ferric gluconate have minimal risks of infusion reactions In very severe cases, RBC transfusion

31 Oral Therapy of Iron Deficiency
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 18 18

32 Journal of Family Practice JUNE 2002 VOL.51, NO.6
Price Matters! Journal of Family Practice JUNE 2002 VOL.51, NO.6

33 Response to oral Iron Therapy
Peak reticulocyte count d. Increased Hb and Hct d. Normal Hb and Hct 2 months Normal iron stores months 19 19

34 Hgb response and MCV response parallel each other after iron replacement

35 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 Bastit et al JCO 26: Henry et al The Oncologist 2007;12:231–242

36 Intravenous Iron formulations
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) (formula dose not account for repletion of body stores)

37 Ferric Carboxy maltose
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 1020 mg 3d apart 1500mg 7d apart Cost Inexpensive Expensive Indication IDA IDA in CKD IDA in CKD/HD +epo + Test dose Yes 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

38 Iv iron for fatigued nonanemic women with serum ferritin <15mg/dl
In patients with baseline serum ferritin < 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P <.005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P<.03). BLOOD, 22 SEPTEMBER 2011 VOLUME 118, NUMBER 12

39 In Conclusion…. IDA is a highly prevalent, but easily treatable condition Oral iron therapies are mostly equivalent in efficacy Infusion reaction rates are very low in iv iron products other than HMW dextran Costs and indication for therapy are important to help decide the best iv iron replacement product for a patient.

40 Iron studies in inflammation and CKD
There is no established goal as to what lab parameters are considered iron deficiency Functional iron deficiency is where iron stores are present in the body but not usable due to Hepcidin Usually normocytic but microcytic anemia in severe cases

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

42 Questions

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