Ironing out Anemia
Jason Hart
Family Medicine Rounds
September 17, 2013.
Disclosures

Previously received honorarium from
Celgene
Objectives





What is the approach to managing iron
deficiency?
What is the prevalence and significance of
anemia in the elderly?
What are the common causes?
What are the appropriate investigations for this
group?
When should you investigate for myelodysplastic
syndrome?
Definition of Anemia

Ideal definition of anemia:


A blood count lower than the person in
question needs to maintain in order to stay in
good health
Defined by the World Health Organization
Women, Hb < 120 g/L
 Men, Hb < 130 g/L

Prevalence
**Overall prevalence of anemia over age 65 is 11%
Approach to Anemia
Fe Def’y
ACD (or normo)
Thall.
Pb
Sideroblastic
Renal Failure
ACD
Lack hematinics
Marrow failure
MCV
Anemia
Hb<120, F
Hb<130, M
Retic Count
Liver Dz/EtOH
Reticulocytosis
MDS (or normo)
Folate/B12
Hypothyroidism
4 H’s:
Hemolysis
Hypoxia
Hemorrhage
Hematinic
response
Iron Deficiency



Average dietary intake of iron is 1010-15 mg
daily
But iron absorption only 10% (1(1-2 mg
daily)
Blood loss of 55-10 mL/day exceeds the
amount of iron the gut can absorb from a
normal diet
Causes of Iron Deficiency


Blood loss
Poor absorption



Partial gastrectomy, celiac disease, bacterial
overgrowth, constitutional variation
(everybody's different)
Poor intake
Higher demand (pregnancy)
Case #1






45 y.o. woman
Mother of 3 kids, works full time
Healthy
Hb of 87, MCV 63, Ferritin <5
Fatigue
Iron supplements not effective
Pitfalls of Managing Iron Deficiency

#1 COMPLIANCE



“I took it, but I didn’
didn’t feel any better so I
stopped””
stopped
I rechecked my hemoglobin after a month,
and it didn’
didn’t go up, so I stopped”
stopped”
“It made me constipated so I stopped”
stopped”
PITFALL #2—
#2—Duration of therapy


Needs longlong-term therapy
Can calculate amount of iron deficient



Usually, if Hb less than 90, deficiency is
approximately 1 g of elemental iron
Need to take iron supplements for many
months before a significant change is seen
If there is ongoing blood loss, the iron
supplement needs to be greater than the
ongoing losses
Pitfall #3: Choice of supplement
Are all Iron supplements equal?
PITFALL #3—
#3—Choice of supplement
Supplement
Dose
Elemental iron/dose
Ferrous sulphate
325 mg
65 mg
Ferrous gluconate
325 mg
36 mg
Ferrous fumarate
325 mg
106 mg
Fer--in
Fer
in--sol (syrup)
5 mL
30 mg
Fer--in
Fer
in--sol (drops)
1 mL
15 mg
Slow-Fe (slow
Slowrelease)
320 mg
60 mg
Pitfall #4—
#4—Poor absorption

Need an acidic environment to absorb iron


PPI’s lessen absorption of iron
PPI’
Take Vitamin C 500 mg with each tablet of
iron
Approach to Managing Iron
Deficiency


Step 1—
1—confirm iron deficiency
Step 2—
2—Investigate and fix underlying
cause


blood loss, poor intake, poor absorption
Step 3—
3—supplement
Distinguishing ACD from Fe Deficiency
Iron
Deficiency
Ferritin
Ferritin < 13
diagnostic
Ferritin >100 not
deficient
Anemia of
Chronic
Disease
Not low
Fe
IBC
Tf Sat.
<15%
>15%
Example of Iron deficiency in the
setting of ACD
Case of
Vasculitis and
renal failure
Anemia of
Chronic
Disease
Ferritin
357
Not low
Fe
3
IBC
33
Tf Sat.
6%
>15%
Step 2: What is the cause?

Rate of GI pathology for iron deficiency is
43--86%
43



Approximately 50% are upper GI cause
Factors predictive of GI pathology are higher
age, positive FOBT, MCV less than 60.
Prevalence of GI malignancy is 66-13%

Predictors are age >50, male gender, Hb less than
90.
Guidelines for GI Investigations

Premenopausal woman with IDA


Rate of malignancy 00-3%
GI pathology seen in 66-30% of premenopausal
woman


Does not require endoscopy unless having:

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Erosive gastritis, H.pylori, NSAID gastropathy
Abdominal symptoms, wt loss >5kg, FOBT positive, or Hb
<100.
Positive family history of two first degree relatives for GI
malignancy, or one first degree relative under age 50
In the absence of symptoms, no investigations
required
Guidelines for GI Investigations

Post-menopausal woman and men with
Postiron deficiency



GI pathology found in 4343-86% of patients
GI malignancies in 66-13%
Look for occult celiac disease

If no response to oral iron then:

Measure tissue antianti-transglutaminase level (TTG)
and IgA level
Gut 2011;60:1309.
Step 3—
3—Supplements



Start with ferrous fumarate 300 mg once
or twice a day
Ferrous fumarate >ferrous
sulphate>ferrous gluconate
Treat a compliant patient for 22-3 months
then check for response.
Heme Complex Iron Supplements




Proferrin
Heme--iron polypeptide
Heme
Evidence of improved
absorption compared to
ferrous fumarate1
Equivalent to IV iron in
anemia in nonnon-dialysis
dependent renal disease2.
Expensive


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Feramax
Polysaccharide iron
complex
Clinical data from 19683.
Presumed to be better
tolerated
Expensive
1 Seligman et al. Nutrition research. 2000;20:1279;
2 Nagaraju et al. BMC Nephrology. 2013;14:64;
3 Sanders JF. Michighan Medicine. 1968;67:726.
IV Iron

Iron Sucrose (Venofer)



Less infusion related reactions compared to
iron dextran
Still carries the risk of anaphylaxis
If giving 200 mg or less, infusion time 30
minutes
Typical infusion is 200 mg IV weekly x 44-5 doses.
 If giving >200 mg then 33-4 hour infusion

Adverse Events with Parenteral
Iron
Chertow et al. Nephrol Dial Transplant 2006;21:378.
Iron Sucrose (Venofer) vs. Iron
Dextran


In the US, if iron sucrose were to replace
low molecular weight iron dextran, 27
fewer life threatening reactions, and 6
fewer deaths per year
Disadvantage—
Disadvantage
—Iron sucrose costs more
Cost of IV Iron in VIHA
Start elemental iron
(Ferrous fumarate 300 mg
qd or bid)
Tolerant to
Treatment?
NO
Switch to second
line* oral therapy
YES
*Second line therapy:
Consider Proferrin,
Feramax,
alternate elemental iron
Responding
to therapy?
(after 2-3 months)
YES
NO
Consider IV Iron
Treat until normal Hb
PLUS 3 months
Monitor for
Recurrence in
6 months
Questions about Iron Deficiency?
Case #2

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74 y.o. male
Hb 107.
Known of anemia for 3 years. No blood
loss, stools negative.
Fatigues by the end of the day, but no
limits to his activities.
No fevers/chills/sweats, Wt stable
Case #2

Past Medical History

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CAD, angioplasty in August 2005
Recurrent renal stones over 5 years. Last
attack 6 months ago

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Has obstructed ureter on CT—
CT—awaiting surgery
Chronic renal failure—
failure—Cr =140, GFR 42
Hypertension, high cholesterol
Meds: Lipitor, micardis, ASA, atenolol
Case #2

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Physical exam=normal except a 2/6 midmidsystolic murmur
Labs: Hb 107, MCV 90, rest of CBC
normal, Cr 140, ferritin 40.
Why is this man anemic?
How would you investigate?
Causes
Causes
 1/3
ACD or Renal Failure
 1/3 Nutritional
 1/3 are Unexplained
Anemia of Chronic Disease

Common causes are cancer, infection,
heart disease, diabetes and chronic
inflammatory disease
Investigations
(Fishing expedition)
Investigations

Nutritional


Malignancy


Ferritin, Fe, IBC, B12, folate
CXR, U/S abdomen, stool for OB, SPE, PSA, mammogram
Anemia of Chronic Disease

Inflammatory condition

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Organ dysfunction

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History and PE for CTD, OA, chronic infection
Hep B/C/HIV
TSH, DM, heart failure (H and PE), Cr, Testosterone
Bone Marrow Disorder

MDS, infiltrative process
Case #2
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Hb 108, MCV 92, rest of CBC normal
Ferritin 158, Fe normal, TIBC normal
Vit B12 low (178), folate normal
Cr 158, GFR 42
SPE normal, U/S abdomen/CXR normal
Testosterone low (5.6), TSH normal
Case #2


Conclusion:
Multifactorial anemia

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
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B12 deficiency
Male menopause
Renal failure
Anemia of chronic disease
?MDS
BONE MARROW BIOPSY?
Unexplained Anemia

Perhaps this is bone marrow etiology?



MDS?
Infiltrative process?
Indication for a bone marrow biopsy:



Severe unexplained anemia
Progressive drop in Hb
If it will change management
Unexplained Anemia


One study (Sweden, 1988) performed
bone marrow biopsies on all elderly
patients with unexplained anemia
The resulting rate of unexplained anemia
remained constant (33%)


Specific diagnosis unlikely
“Early
Early”” myelodysplastic syndrome is a difficult
diagnosis to make
Will a biopsy change management?


All therapies for myelodysplastic syndrome
begin once transfusion dependent.
Early treatment does not lead to better
outcomes

No urgency to make the diagnosis
Anemia Of The Elderly
Summary



Investigation should be geared to identifying the
common, treatable causes while ruling out
serious causes
Manage other comorbidities
Regular surveillance of CBC looking for warning
signs of bone marrow disease


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Hb less than 100
Neutrophils less than 1.0
PLT less than 50
Anemia Of The Elderly
Summary


Up to 2525-30% of elderly patients are
anemic
Etiology Rule of Thirds:



1/3 nutritional
1/3 ADC or renal insufficiency
1/3 Unexplained anemia
Questions?