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
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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