Sandra I. Austhof, MS, RD, LD, CNSC
2015 Dietitians in Nutrition Support Symposium
Baltimore, MD
June 12, 2015
1

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.
2

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;38:656-672.
Abbaspour N, et al. J Res Med Sci 2014; 19(2):164-174.
deBack DZ, et al. Front Physiol 2014;5:1-11.
3




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:
Ascorbic acid and meat,
poultry, fish.
Hinders absorption:
Milk and dairy products,
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;38:656-672.
4
5

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;371:1324-1331.
Chan LN, et al. JPEN 2014;38:656-672.
Abbaspour N, et al. J Res Med Sci 2014;19(2):164-174
6

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;371:1324-1331.
7

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


1Aigner
Inflammatory state – increased Hepcidin
Impaired duodenal absorption
E, et al. Nutrients 2014;6:3587-3600.
8

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;23:128-141
9

Increased loss



Increased demand


Acute or chronic bleeding
Multiple surgeries
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.
10

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;23:128-141.
11
Lab Test
Normal values
Comments
Hemoglobin
• Women ≥12.0 g/dL
• Iron-containing protein in RBC
that carries oxygen.
• Most commonly used.
• Inexpensive.
• Easy to perform.
• Pregnant women ≥11.0 g/dL
• Men ≥13.0 g/dL
Hematocrit
• Women >36 %
• Pregnant women >33 %
• Percentage of blood volume
that is made up of red blood
cells.
• Men >39 %
Mean Corpuscular Volume
• 80-100 fL
• Average volume of red cells.
• Low in iron deficiency anemia
indicating small RBCs.
Red Cell Distribution Width
• 11.5-15 %
• 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; http://www.who.int/vmnis/indicators/hemoglobin.pdf
12
A
Component
WBC
RBC
Hemoglobin
Hematocrit
MCV
MCH
MCHC
RDW-CV
B
Latest Ref Rng
Component
Latest Ref Rng
3.70 - 11.00 k/uL
3.90 - 5.20 m/uL
11.5 - 15.5 g/dL
36.0 - 46.0 %
80.0 - 100.0 fL
26.0 - 34.0 pG
30.5 - 36.0 g/dL
11.5 - 15.0 %
WBC
RBC
Hemoglobin
Hematocrit
MCV
MCH
MCHC
RDW-CV
3.70 - 11.00 k/uL
3.90 - 5.20 m/uL
11.5 - 15.5 g/dL
36.0 - 46.0 %
80.0 - 100.0 fL
26.0 - 34.0 pG
30.5 - 36.0 g/dL
11.5 - 15.0 %
4.87
4.91
13.3
39.7
80.9
27.1
33.5
13.5
C
Component
Latest Ref Rng
WBC
RBC
Hemoglobin
Hematocrit
MCV
MCH
MCHC
RDW-CV
3.70 - 11.00 k/uL
4.20 - 6.00 m/uL
13.0 - 17.0 g/dL
39.0 - 51.0 %
80.0 - 100.0 fL
26.0 - 34.0 pG
30.5 - 36.0 g/dL
11.5 - 15.0 %
8.77
3.83 (L)
11.1 (L)
34.6 (L)
90.3
29.0
32.1
13.5
D
5.27
3.95 (L)
9.4 (L)
30.3 (L)
76.7 (L)
23.8 (L)
31.0
15.9 (H)
Component
Latest Ref Rng
5/7/2014
WBC
RBC
Hemoglobin
Hematocrit
MCV
MCH
MCHC
RDW-CV
3.70 - 11.00 k/uL
3.90 - 5.20 m/uL
11.5 - 15.5 g/dL
36.0 - 46.0 %
80.0 - 100.0 fL
26.0 - 34.0 pG
30.5 - 36.0 g/dL
11.5 - 15.0 %
5.98
3.56 (L)
11.0 (L)
35.8 (L)
100.6 (H)
30.9
30.7
17.4 (H)
13
Lab Test
Normal values
Comments
Iron
• Male: 60-170 mcg/dL
• Female: 50-170 mcg/dL
•
•
Ferritin
• Male: 12-300 ng/mL
• Female: 12-150 ng/mL
•
•
•
•
•
TIBC
• 240-450 mcg/dL
Measure of all iron in the body
bound mostly to transferrin
Low in iron deficiency anemia
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)
• Measures amount of circulating
transferrin that is available to bind
iron
• Elevated in iron deficiency anemia
14
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
• 0.5-1.5%
• 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
15
Lab Test
Normal Values
Comments
Serum Transferrin Receptors
(TfR)
• Male: 2.2-5 mg/L
• A glycoprotein that transfers
circulating iron into RBCs
• Female: 1.9-4.4 mg/L
• Levels not established for
pregnant women,
children.
• 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
16
B
A
Component
Iron
TIBC
Transferrin Saturation
Ferritin
Latest Ref Rng
30 - 140 ug/dL
210 - 415 ug/dL
11 - 46 %
9.0 - 150.0 ng/mL
89
348
26
90.9
Component
Latest Ref Rng
11/21/2013
Iron
TIBC
Transferrin Saturation
Ferritin
30 - 140 ug/dL
210 - 415 ug/dL
11 - 46 %
18.0 - 300.0 ng/mL
18 (L)
406
10 (L)
17.0 (L)
C
Component
Iron
TIBC
Transferrin Saturation
Ferritin
Latest Ref Rng
30 - 140 ug/dL
210 - 415 ug/dL
11 - 46 %
18.0 - 300.0 ng/mL
11/25/2008
19 (L)
221
9 (L)
419.8 (H)
17
LAB
NORMAL LEVELS
FE DEFICIENCY
without ANEMIA
FE DEFICIENCY
with ANEMIA
ANEMIA of
CHRONIC DISEASE
Hemoglobin (g/dL)
Men
Women
>13
>12
>13
>12
<13
<12
<13
<12
MCV (fL)
80-100
80-100
(normal)
<80
(low)
<80
(low to low normal)
Ferritin (ng/mL)
100 ± 60
10 – 20
(low)
<10
(low)
>100
(high)
Iron (µg/dL)
115 ± 50
<60 – 115
(low)
<40
(low)
Low
TIBC (µg/dL)
330 ± 30
360
(high)
410
(high)
Low
Transferrin Sat (%)
35 ± 15
<15 – 30
(low)
<15
(low)
Low-normal
Camaschella C. NEJM. 2015;372:1832-1843.
Clark S. Nutr Clin Prac. 2008;23:128-141.
18
Oral therapy
IV therapy
•
Preferred line of treatment
•
Provides faster response rate
•
Safer, cost-effective
•
Hgb <10 g/dL
•
GI-related side effects common
•
Lack of response to oral iron
•
Elemental iron/d dose 100-200
mg
•
Malabsorption states (e.g., IBD,
Celiac disease, SBS)
•
Ferrous salts best absorbed
•
•
Take with ascorbic acid 250 mg
(or ½ cup OJ)
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;38:656-672.
Bayraktar UD et al. World J Gastroenterol 2010;16:2720-2725.
19
Oral Iron
Treatment
Brand Name
Tablet dose
Elemental
Iron
Ferrous sulfate
Feosol
325 mg
65 mg
Feosol elixir
5 mL
44 mg
Fergon
325 mg
36 mg
Fergon elixir
5 mL
34 mg
Feostat
325 mg
106 mg
oral suspension
5 mL
100 mg
Iron
polysaccharide
Niferex
150 mg
100 mg
(better tolerated)
Niferex Elixir
5 mL
100 mg
Ferrous
gluconate
Ferrous fumarate
 Goal: 100 – 200 mg Elemental Iron per day
 Enteric-coated iron tabs better tolerated but less effective (may not release in
duodenum)
20
IV Iron
Treatment
Brand Name
Iron Dextran –
high molecular weight
DexFerrum
Iron Dextran –
low molecular weight
INFeD
Ferric Gluconate
Ferrlecit
Nulecit
(50 mg/mL elemental
Fe)
(12.5 mg/mL elemental
Fe)
Iron Sucrose
Venofer
(20 mg/mL elemental
Fe)
Ferumoxytol
Feraheme
(30 mg/mL elemental
Fe)
Ferric
carboxymaltose
Injectafer
(50 mg/mL elemental
Fe)
Single Dose
No longer
recommended.
(Black Box Warning)
Comments
>Compatible with 2 in1 PN
>Can be given in 1 high dose
>Highest reaction rate
>Test dose required
500-1000 mg over
1 hr
>Compatible with 2 in1 PN
>Can be given in 1 high dose
>Test dose required
Max 125 mg
over 20-30
mins
>No test dose required
>Can cause hypotension
>Administration requires several
clinic visits to provide 1000 mg
200 mg over
60 mins
>No test dose required
>Best tolerated
>Can cause hypotension
>Expensive
>Administration requires several
clinic visits to provide 1000 mg
510 mg over
15 mins
>Can cause severe hypotension
>Administration: 2 doses 3-8
days apart
Up to 750 mg
over 15 mins
>Approved by FDA July 2013
>Can cause hypophosphatemia
and HTN
(<50 kg give 15 mg/kg
on 1st day)
21
Iron (mg) = 0.3 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
13.5
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
22
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
23
•
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
0.7 -1 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;23:128-141.
Chan LN, et al. JPEN 2014;38:656-672.
DeLoughery TG. NEJM 2014;371:1324-1331.
24

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.
25
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
26
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
27
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
28
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
29
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
30

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
31
32