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IRON DEFICIENCY ANEMIA Rakhi Naik, MD, MHS Assistant Professor of Medicine & Oncology, Division of Hematology.

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Presentation on theme: "IRON DEFICIENCY ANEMIA Rakhi Naik, MD, MHS Assistant Professor of Medicine & Oncology, Division of Hematology."— 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 KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5

5

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

8 Hemoglobin in RBC Schechter BLOOD, 15 NOVEMBER 2008 VOLUME 112, NUMBER 10 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

9 Iron Absorption Food sources supply: 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 25% bioavailability

10 Iron absorption from food Iron Absorption (% of dose) Veal muscle Hemoglobin Fish muscle Veal liver Ferritin Soy beans Wheat Lettuce Corn Black beans Spinach Rice Non-heme iron Heme iron

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

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

13 The iron cycle Pietrangelo, NEJM 2004:350:2383

14 Iron Losses Iron is closely conserved in humans <0.05% of iron is lost per day normally 1. Very small amounts in urine, bile and sweat 2. Cells shed from skin, intestinal and urinary tracts 3. Menstrual blood loss 4. Pregnancy and lactation Humans have NO other physiologic means to excrete excess iron

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

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

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

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)

20 Marked hypochromasia, microcytosis

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

22 Sequential Changes in IDA NORMAL DEPLETED IRON IRONSTORES IRONDEFICIENCY IRONDEFICIENCYANEMIA FERRITIN IRON SATURATION MCV & Hb & Hct

23 Differential for low serum ferritin 1. Iron Deficiency 2. Iron Deficiency

24 CBC in Iron Deficiency Anemia

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

27 IDA vs. Inflammation FerritinIDAInflammation Serum Iron Transferrin sat sfTR / log Ferr Marrow Iron No 

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

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

32 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 Hct2 months Normal iron stores4 - 5 months

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 Lmw Iron Dextran Iron Sucrose Ferric Gluconate FerumoxytolFerric Carboxy maltose Administered Dosage 100mg200 mg125 mg510mg750mg Total Dose Infusion 1000 mgno 1020 mg 3d apart 1500mg 7d apart CostInexpensive Expensive IndicationIDAIDA in CKDIDA in CKD/HD +epo IDA in CKDIDA + IDA in CKD Test doseYesnone None AdministrationIv (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 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 <20%<100 ESRD <30%<500

42 Questions


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