iron deficiency anemia rakhi naik, md, mhs assistant professor of medicine & oncology, division...
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IRON DEFICIENCY ANEMIA
Rakhi Naik, MD, MHS
Assistant Professor of Medicine & 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
• Understand modalities of treatment of iron deficiency and anemia
Global Burden of Anemia
KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5
KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5
KASSEBAUM et al BLOOD, 30 JANUARY 2014 x VOLUME 123, NUMBER 5
Iron Distribution
Adult male has ~4g total body
iron stores
Andrews NEJM, 23 DEC 1999 x VOLUME 341, Number 26
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
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
Iron absorption from food
Iron Absorption (% of dose)
0 5 10 15 20 25
Veal muscle
HemoglobinFish muscle
Veal liverFerritin
Soy beansWheat
LettuceCorn
Black beansSpinach
Rice
Non-hemeiron
Hemeiron
• 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 Storage
• Ferritin• multi-subunit protein• primarily intracellular• some in plasma
• Hemosiderin• insoluble form of ferritin
• visible microscopically
The iron cycle
Pietrangelo, NEJM 2004:350:2383
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 sweat2. Cells shed from skin, intestinal and urinary tracts3. Menstrual blood loss4. Pregnancy and lactation• Humans have NO other physiologic means to excrete excess iron
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
Andrews NEJM, 23 DEC 1999 x VOLUME 341, Number 26
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
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
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)
Marked hypochromasia,
microcytosis
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
ErythroblastTfR+
Fe
Transferrin
Sequential Changes in IDA
NORMALDEPLETED
IRONSTORES
IRONDEFICIENCY
IRONDEFICIENCY
ANEMIA
FERRITIN
IRON SATURATION
MCV & Hb & Hct
Differential for low serum ferritin1. Iron Deficiency
2. Iron Deficiency
CBC in Iron Deficiency Anemia
Lab values in severe IDA
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
IDA vs. Inflammation
Ferritin
IDA Inflammation
Serum Iron
Transferrin sat
sfTR / log Ferr
Marrow Iron No D
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
Iron stain of bone marrow
Iron Deficient MarrowPrussian Blue Stain
Normal MarrowPrussian Blue Stain
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
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
Price Matters!
Journal of
Family Practic
e JUNE 2002
VOL.51,
NO.6
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 months
Hgb response and MCV response parall
el each other after iron
replacement
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: 1511-1618 2008 Henry et al The Oncologist 2007;12:231–242
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)
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 no 1020 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 infusion
Iv iron for fatigued nonanemic women with serum ferritin <15mg/dl
BLOOD, 22 SEPTEMBER 2011 VOLUME 118, NUMBER 12
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.
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
Iron deficiency in inflammation and CKD
Transferrin sats % Ferritin
Inflammation <20% <100
CKD <20% <100
ESRD <30% <500
