1. Iron Deficiency Anemia: What the Dietitian Needs to Know
Sandra I. Austhof, MS, RD, LD, CNSC
2015 Dietitians in Nutrition Support Symposium
Baltimore, MD
June 12, 2015

2. Objectives
Discuss iron metabolism and the etiology of iron deficiency anemia.
Be able to interpret the Complete Blood Count (CBC) and iron laboratory tests to determine iron deficiency anemia verses anemia from inflammation.
Identify the correct iron treatment for oral and intravenous therapy.

3. Iron Metabolism Found in every living cell
60% in the form of hemoglobin in circulating erythrocytes
20% stored as ferritin, primarily in the liver
15% myoglobin
~5% enzymes and other proteins
Transports oxygen, DNA synthesis, electron transport, cell proliferation
Major iron supply for hemoglobin synthesis:
Diet
Recycling from old erythrocytes by macrophages
Tightly regulated to prevent iron toxicity > tissue damage
1-2 mg lost and absorbed daily to maintain normal homeostasis
No excretory pathway for iron except blood loss & basal losses (sloughing of skin cells & mucosal surfaces, sweat, urine, stool)
Chan LN, et al. JPEN 2014;38:
Abbaspour N, et al. J Res Med Sci 2014; 19(2):
deBack DZ, et al. Front Physiol 2014;5:1-11.

4. Iron Absorption Duodenum and proximal jejunum (~1-2 mg iron daily)
Colon - only one tenth of duodenal iron absorbed in colon.
Heme: animal sources (15-35% absorbed)
Non-Heme: plant sources (2-20% absorbed)
Enhances absorption: Hinders absorption:
Ascorbic acid and meat, Milk and dairy products,
poultry, fish. calcium, eggs, tea, coffee,
spinach, legumes, and fiber.
Antacids, H2 antagonists, proton pump inhibitors.
Concurrent intake of zinc or manganese supplement.
Chan LN, et al. JPEN 2014;38:

5. Absorption

6. Erythropoiesis
Erythropoietin triggers stimulation of red blood cell production stimulating heme and globin synthesis.
Hemoglobin synthesis not only requires adequate supply of iron, but also, Copper, Vitamin B12, Folate, Biotin, Vitamin B6, Zinc, and Vitamin A, and normal production of protoporphyrin and globin.
Rate of hemoglobin synthesis is determined by
the availability of transferrin iron and levels
of intracellular heme.
Heme synthesis begins in mitochondria by
a series of biochemical reactions
Fe++ combines with protoporphyrin to form Heme
Excess porphyrin binds to zinc (zinc protoporphytin)
Globin synthesized in cytosol combines with Heme once it exits the mitochondria.
Khan AA, et al. Biochim Biophys Acta. 2011; 1813(5): 668–682
DeLoughery TG. NEJM 2014;371:
Chan LN, et al. JPEN 2014;38:
Abbaspour N, et al. J Res Med Sci 2014;19(2):

7. Iron Deficiency Anemia
Most common form of anemia
A condition where there is a lack of iron delivery to the heme group of hemoglobin, the protein that transports oxygen in blood
Blood cells are abnormally small (microcytic) and pale (hypochromic)
DeLoughery TG. NEJM 2014;371:

8. Anemia from Inflammation
The restriction of iron delivery to the heme group
Renal production of Erythropoietin suppressed
Hepcidin production blocks release of iron from enterocytes & other cells
Obesity – emerging as risk factor for Fe def anemia1
Inflammatory state – increased Hepcidin
Impaired duodenal absorption
1Aigner E, et al. Nutrients 2014;6:

9. Stages of Iron Deficiency Anemia
Stage 1 – Negative iron balance (iron intake does not meet daily need; normocytic, normochromic)
Stage 2 - Iron Depletion (iron stores exhausted; Hgb still normal)
Stage 3 – Iron-deficient erythropoiesis (erythrocytes deficient in iron; hypochromic)
Stage 4 – Iron deficiency anemia (severe iron depletion blood levels cannot meet daily needs; Hgb depleted)
Clark S. Nutr Clin Prac.2008;23:

10. Etiology of Iron Deficiency
Increased loss
Acute or chronic bleeding
Multiple surgeries
Increased demand
Rapid periods of growth – pregnancy, newborns, infants, young children, adolescents, menstruating women.
Decreased intake or absorption
Lack of dietary iron or consuming foods that inhibit absorption
Reduction of gastric acid (due to proton-pump inhibitors, H2 blockers)
Damage to intestinal lining of duodenum/prox jejunum (e.g., Crohn’s, Celiac disease)
Long-term parenteral nutrition therapy without iron therapy
Decreased production of red cells
Erythropoietin deficiency (ESRD) – due to lack of erythropoietin production by kidneys to promote formation of RBC in bone marrow
It’s important to know the cause of anemia before treating.

11. Clinical Manifestations
Feeling weak or tired more often
than usual.
Headaches / Problems concentrating.
Brittle or spoon-shaped nails (koilonykia).
Desire to eat ice or other non-food things (pica).
Pale skin, gums, and nail beds.
Shortness of breath.
Rapid or irregular heartbeats.
Glossitis - Smooth, shiny, reddened tongue.
Clark S. Nutr Clin Prac. 2008;23:

12. Laboratory Data Complete Blood Count (CBC)
Lab Test
Normal values
Comments
Hemoglobin
Women ≥12.0 g/dL
Pregnant women ≥11.0 g/dL
Men ≥13.0 g/dL
Iron-containing protein in RBC that carries oxygen.
Most commonly used.
Inexpensive.
Easy to perform.
Hematocrit
Women >36 %
Pregnant women >33 %
Men >39 %
Percentage of blood volume that is made up of red blood cells.
Mean Corpuscular Volume fL
Average volume of red cells.
Low in iron deficiency anemia
indicating small RBCs.
Red Cell Distribution Width %
Represents the heterogeneity of
red blood cell volume width.
Helps determine cause of anemia.
Elevated in Fe Def Anemia (anisocytosis-red blood cells of unequal sizes).
WHO;

13. examples of Complete Blood Count
Component
Latest Ref Rng
WBC
k/uL
4.87
RBC
m/uL
4.91
Hemoglobin
g/dL
13.3
Hematocrit %
39.7
MCV fL
80.9
MCH pG
27.1
MCHC
g/dL
33.5
RDW-CV %
13.5
Component
Latest Ref Rng
WBC
k/uL
8.77
RBC
m/uL
3.83 (L)
Hemoglobin
g/dL
11.1 (L)
Hematocrit %
34.6 (L)
MCV fL
90.3
MCH pG
29.0
MCHC
g/dL
32.1
RDW-CV %
13.5 C D
Component
Latest Ref Rng
WBC
k/uL
5.27
RBC
m/uL
3.95 (L)
Hemoglobin
g/dL
9.4 (L)
Hematocrit %
30.3 (L)
MCV fL
76.7 (L)
MCH pG
23.8 (L)
MCHC
g/dL
31.0
RDW-CV %
15.9 (H)
Component
Latest Ref Rng
5/7/2014
WBC
k/uL
5.98
RBC
m/uL
3.56 (L)
Hemoglobin
g/dL
11.0 (L)
Hematocrit %
35.8 (L)
MCV fL
100.6 (H)
MCH pG
30.9
MCHC
g/dL
30.7
RDW-CV %
17.4 (H)

14. Iron Studies Lab Test Normal values Comments Iron Male: 60-170 mcg/dL
Female: mcg/dL
Measure of all iron in the body bound mostly to transferrin 
Low in iron deficiency anemia
Ferritin
Male: ng/mL
Female: ng/mL
Stored iron 
Low in iron deficiency anemia 
Most sensitive and cost-effective indicator of iron deficiency anemia  
May be elevated during
infection even if iron
stores are low 
High levels may suggest anemia of chronic disease since normal or elevated levels can occur during inflammation, malignancy
or conditions causing organ or
tissue damage (e.g., arthritis,
hepatitis)
TIBC
mcg/dL
Measures amount of circulating transferrin that is available to bind iron
Elevated in iron deficiency anemia

15. Iron Studies (CON’T) Lab Test Normal values Comments
Transferrin saturation
20-50%
The percentage of how much iron is actually bound to available transferrin
Serum iron ÷ TIBC x 100 = % Sat
Example: 50 ÷ 475 x 100 = 10.5%
Low in iron deficiency anemia
Reticulocyte count %
Measures circulating immature RBC
Low in Fe def anemia.
Zinc (Erythrocyte) Protoporphytin (ZPP)
≤40 µmol/mol heme
Elevated in Fe Def Anemia
(>70 mmol/mol heme)
If iron levels low, zinc binds with protoporphyrin IX to produce ZPP instead of heme

16. Iron Studies (CON’T) Lab Test Normal Values Comments
Serum Transferrin Receptors (TfR)
Male: mg/L
Female: mg/L
Levels not established for pregnant women, children.
A glycoprotein that transfers circulating iron into RBCs
Elevated in Fe Def Anemia due to increase in transferrin receptors on RBCs to maximize Fe uptake
Sensitive and not affected by
inflammation
Not widely available

17. Examples of iron studiesB A
Component
Latest Ref Rng
Iron
ug/dL 89
TIBC
ug/dL
348
Transferrin Saturation % 26
Ferritin
ng/mL
90.9
Component
Latest Ref Rng
11/21/2013
Iron
ug/dL
18 (L)
TIBC
ug/dL
406
Transferrin Saturation %
10 (L)
Ferritin
ng/mL
17.0 (L) C
Component
Latest Ref Rng
11/25/2008
Iron
ug/dL
19 (L)
TIBC
ug/dL
221
Transferrin Saturation %
9 (L)
Ferritin
ng/mL
419.8 (H)

18. LAB
NORMAL LEVELS
FE DEFICIENCY without ANEMIA
FE DEFICIENCY with ANEMIA
ANEMIA of CHRONIC DISEASE
Hemoglobin (g/dL)
Men
Women
>13
>12
<13
<12
MCV (fL)
80-100
(normal)
<80
(low)
(low to low normal)
Ferritin (ng/mL)
100 ± 60
10 – 20
<10
 (low)
>100
(high)
Iron (µg/dL)
115 ± 50
<60 – 115
<40
Low
TIBC (µg/dL)
330 ± 30
360
410
Transferrin Sat (%)
35 ± 15
<15 – 30
<15
Low-normal
Camaschella C. NEJM. 2015;372:
Clark S. Nutr Clin Prac. 2008;23:

19. Treatment > Goal to restore Hemoglobin and iron stores
Oral therapy
Preferred line of treatment
Safer, cost-effective
GI-related side effects common
Elemental iron/d dose mg
Ferrous salts best absorbed
Take with ascorbic acid 250 mg (or ½ cup OJ)
IV therapy
Provides faster response rate
Hgb <10 g/dL
Lack of response to oral iron
Malabsorption states (e.g., IBD, Celiac disease, SBS)
Iron loss too great (ongoing bleeding)
Given as intermittent IV or injection
Blood transfusion indicated if Hbg <7.0 g/dL with SOB, extreme fatigue.
Chan LN, et al. JPEN 2014;38:
Bayraktar UD et al. World J Gastroenterol 2010;16:

20. Oral Treatment Oral Iron Treatment Brand Name Tablet dose
Elemental Iron
Ferrous sulfate
Feosol
Feosol elixir
325 mg
5 mL
65 mg
44 mg
Ferrous gluconate
Fergon
Fergon elixir
36 mg
34 mg
Ferrous fumarate
Feostat
oral suspension
106 mg
100 mg
Iron polysaccharide
(better tolerated)
Niferex
Niferex Elixir
150 mg
Goal: 100 – 200 mg Elemental Iron per day
Enteric-coated iron tabs better tolerated but less effective (may not release in duodenum)

21. IV Treatment IV Iron Treatment Brand Name Single Dose Comments
Iron Dextran –
high molecular weight
DexFerrum
No longer
recommended.
(Black Box Warning)
>Compatible with 2 in1 PN
>Can be given in 1 high dose
>Highest reaction rate
>Test dose required
low molecular weight
INFeD
(50 mg/mL elemental Fe)
mg over
1 hr
Ferric Gluconate
Ferrlecit
Nulecit
(12.5 mg/mL elemental Fe)
Max 125 mg
over 20-30
mins
>No test dose required
>Can cause hypotension
>Administration requires several clinic visits to provide 1000 mg
Iron Sucrose
Venofer
(20 mg/mL elemental Fe)
200 mg over
60 mins
>Best tolerated
>Expensive
>Administration requires several clinic visits to provide 1000 mg
Ferumoxytol
Feraheme
(30 mg/mL elemental Fe)
510 mg over
15 mins
>Can cause severe hypotension
>Administration: 2 doses 3-8
days apart
Ferric
carboxymaltose
Injectafer
Up to 750 mg
over 15 mins
(<50 kg give 15 mg/kg on 1st day)
>Approved by FDA July 2013
>Can cause hypophosphatemia and HTN

22. Calculating IV Iron Repletion Dose
Iron (mg) = x Body weight (lbs) x (100 – [actual Hgb (g/dl) x 100/desired Hgb]
Example: (Weight-154 lbs; Hgb–10.3g/dL; Target Hemoglobin: Men
Women 12.5
Iron (mg) = 0.3 x 154 lbs x (100 – [10.3 g/dL x 100/12.5]
Iron (mg) = 46.2 x (100 – [82.4])
Iron (mg) = 813 mg

23. IV Iron Treatment Two examples of how to give 813 mg IV iron…
1.) IV Iron Sucrose: 200 mg per dose per week given over 60 mins for a total of 4 doses
2.) IV Iron Dextran (LMW):
a.) Test dose required (25 mg by slow IV push)
b.) 1000 mg per dose given over 1 hour.
i.) extra mg iron given can go to stores

24. Monitoring
Pica or restless leg syndrome should disappear once therapy begun.
Hemoglobin should begin to improve by 1-2 g/dL the first 2 weeks then
g/dL per week.
Ferritin may take up to 32 weeks to improve.
If Reticulocyte count increases within 4 weeks, treatment is probably effective.
Inadequate response may be related to continued blood loss (e.g., heavy menses or analgesic use), inflammation, ineffective absorption, or poor compliance.
Once hemoglobin normal, monitor CBC and iron studies every 3-4 months up to a year.
Continue therapy until iron stores replete.
Clark SF. Nutr Clin Prac. 2008;23:
Chan LN, et al. JPEN 2014;38:
DeLoughery TG. NEJM 2014;371:

25. Case Study
A 42 year old female with a history of ulcerative colitis and heavy menstrual losses was admitted to the hospital for fatigue and weakness. Her surgical history showed that she had total abdominal colectomy one year ago.
A diet history is obtained which shows that she consumes hot cereal with a banana and hot tea for breakfast; pasta and canned fruit for lunch; and chicken or fish, potatoes or rice with a cooked vegetable for dinner. She avoids red meat and craves ice chips.
Her CBC reveals: Hemaglobin-10.3, Hematocrit-25.0, Mean Cell Volume-77, Red Cell Distribution Width-17%, C-reactive protein: 1.0.
Weight: 60 kg (132 lbs); Heart rate: 105; Respiratory rate: 19; Blood pressure: 125/85.
You suspect iron deficiency anemia. You examine the patient using the Nutrition-focused physical assessment.

26. Question 1
What physical characteristics are you looking for to confirm a diagnosis of iron deficiency anemia?
A.) Pallor, easy pluckable hair, koilonychia
B.) Pallor, koilonychia, glossitis
C.) Koilonychia, angular stomatitis, dry skin
D.) Koilonychia, bleeding gums, glossitis

27. Question 2
What laboratory data would be best to order next to confirm iron deficiency anemia?
A.) Ferritin, red blood cell count, serum iron, transferrin saturation percent
B.) Ferritin, serum iron, red cell distribution width, total iron binding capacity
 C.) Ferritin, total iron binding capacity, serum iron, transferrin saturation percent
D.) Ferritin, transferrin saturation percent, total iron binding capacity, mean cell volume

28. Question 3 What is the most effective iron treatment for this patient?
A.) Oral ferrous sulfate one 325 mg tab three times per day
B.) Intravenous iron sucrose 200 mg/dose each week for 5 doses over 5 weeks.
C.) Oral ferrous gluconate one 125 mg tab per day
D.) Intravenous infusion of low molecular weight iron dextran 1000 mg over 3 hours

29. Question 4
The patient received 325 mg ferrous sulfate TID, however, developed nausea and constipation 3 weeks into the therapy and had to stop. What would be the next best iron therapy?
A.) Intravenous iron sucrose 200 mg/dose each week for 5 doses over 5 weeks. 
B.) Oral ferrous gluconate one 150 mg tab twice per day 
C.) Oral iron polysaccharide two 150 mg tabs per day
D.) Oral ferrous fumarate one 325 mg tabs four times per day

30. Question 5 A.) Ferritin and hemoglobin
The patient tolerated her new iron treatment and has been taking it for 2 months. Which of the labs listed below would you expect to be in normal range at this point?
A.) Ferritin and hemoglobin
B.) Reticulocyte count, ferritin
C.) Hemoglobin, reticulocyte count   
D.) Hemoglobin, serum iron

31. Summary Fe Deficiency Anemia most common form of anemia
Diagnosis is confirmed with Hemoglobin and Ferritin levels due to highest accuracy in identification
Dietitian completes Nutrition Focused Physical Exam to confirm clinical diagnosis
Oral iron attempted first
IV iron used if oral iron not tolerated, malabsorptive state, severe case of iron deficiency anemia
Close monitoring required to restore Hemoglobin and iron stores

32. Questions