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Iron  Deficiency anemia Rakhi Naik, MD, MHS Iron  Deficiency anemia Rakhi Naik, MD, MHS

Iron Deficiency anemia Rakhi Naik, MD, MHS - PowerPoint Presentation

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Iron Deficiency anemia Rakhi Naik, MD, MHS - PPT Presentation

Assistant Professor of Medicine amp Oncology Division of Hematology Disclosures None 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 ID: 677213

ida iron anemia deficiency iron ida deficiency anemia blood ferritin volume absorption number serum inflammation oral heme marrow transferrin

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Slide1

Iron Deficiency anemia

Rakhi Naik, MD, MHSAssistant Professor of Medicine & Oncology, Division of HematologySlide2

Disclosures

NoneSlide3

Objectives

Understand the basic physiology of iron absorption, transport and storageUnderstand the causes of iron deficiency and the compensatory responses seen in clinical lab testsUnderstand modalities of treatment of iron deficiency and anemiaSlide4

Global Burden of Anemia

KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5Slide5

KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5Slide6

KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5Slide7

Iron Distribution

Adult male has ~4g total body

iron stores

Andrews

NEJM, 23 DEC 1999 x VOLUME 341, Number 26Slide8

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 10Slide9

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% bioavailabilitySlide10

Iron absorption from food

Iron Absorption (% of dose)

0

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

ironSlide11

Transferrin – plasma iron transporter protein. Carries less than 1% of total body iron

Ferritin – intracellular storage of ironHemosiderin – long term iron storage poolSlide12

Iron Storage

Ferritinmulti-subunit proteinprimarily intracellularsome in plasma

Hemosiderin

insoluble form of ferritin

visible microscopicallySlide13

The iron cycle

Pietrangelo,

NEJM

2004:350:2383Slide14

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 ironSlide15

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 infantsSlide16

Andrews

NEJM, 23 DEC 1999 x VOLUME 341, Number 26Slide17

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, irritabilitySlide18

Other features of IDA

P

agophagia - craving ice

Pica - craving of nonfood substances

e.g., dirt, clay, laundry starch

G

lossitis - smooth tongue

Restless Legs

angular stomatitis - cracking of corners of mouth

K

oilonychia - thin, brittle, spoon-shaped fingernailsSlide19

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)Slide20

Marked hypochromasia, microcytosisSlide21

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

TransferrinSlide22

Sequential Changes in IDA

NORMAL

DEPLETED

IRON

STORES

IRON

DEFICIENCY

IRON

DEFICIENCY

ANEMIA

FERRITIN

IRON SATURATION

MCV & Hb & HctSlide23

Differential for low serum ferritin

Iron DeficiencyIron DeficiencySlide24

CBC in Iron Deficiency AnemiaSlide25

Lab values in severe IDASlide26

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 receptorSlide27

IDA vs. Inflammation

Ferritin

IDA

Inflammation

Serum Iron

Transferrin sat

sfTR / log

F

err

Marrow Iron

No

DSlide28

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

Punnonen, K, Blood 1997; 89:1052Slide29

Iron stain of bone marrow

Iron Deficient Marrow

Prussian Blue Stain

Normal Marrow

Prussian Blue StainSlide30

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 transfusionSlide31

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 absorptionSlide32

Price Matters!

Journal of Family Practice JUNE 2002 VOL.51, NO.6Slide33

Response to oral Iron Therapy

Peak reticulocyte count 7 - 10 d.

Increased Hb and Hct 14 - 21 d.

Normal Hb and Hct 2 months

Normal iron stores 4 - 5 monthsSlide34

Hgb response and MCV response parallel each other after iron replacementSlide35

Indications for iv ironSevere symptomatic anemia requiring accelerated erythropoesis

Failure of oral iron from g.i intolerance Failure of oral iron due to absorption issuesH 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: 1511-1618 2008

Henry et al The Oncologist 2007;12:231–242Slide36

Intravenous Iron formulationsHigh 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)Slide37

Lmw Iron

DextranIron Sucrose

Ferric

Gluconate

Ferumoxytol

Ferric Carboxy maltose

Administered Dosage

100mg

200

mg

125 mg

510mg

750mgTotal Dose Infusion1000 mgnono1020 mg 3d apart 1500mg 7d apart

Cost

Inexpensive

Inexpensive

Inexpensive

Expensive

Expensive

Indication

IDA

IDA in CKD

IDA in CKD/HD +epo

IDA in CKD

IDA

+

IDA in CKD

Test dose

Yes

none

none

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 infusionSlide38

Iv iron for fatigued nonanemic

women with serum ferritin <15mg/dl

BLOOD, 22 SEPTEMBER 2011 VOLUME 118, NUMBER 12Slide39

In Conclusion….

IDA is a highly prevalent, but easily treatable conditionOral iron therapies are mostly equivalent in efficacyInfusion reaction rates are very low in iv iron products other than HMW dextranCosts and indication for therapy are important to help decide the best iv iron replacement product for a patient.Slide40

Iron studies in inflammation and CKDThere 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 HepcidinUsually normocytic but microcytic anemia in severe casesSlide41

Iron deficiency in inflammation and CKD

Transferrin

sats

%

Ferritin

Inflammation

<20%

<100

CKD

<20%

<100

ESRD

<30%

<500Slide42

Questions

rakhi@jhmi.edu