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The Uniferon Handbook

A pen-side resource tool for accurate


diagnosis and effective treatment
of iron deficiency anaemia.

Table of Contents
Introduction and the F.A.C.T Program
About this handbook......................................................................3
About Pharmacosmos and Uniferon.........................................4-5
What is the F.A.C.T program and its benefits?...........................6-7
Industry-Accepted Iron Standards
Why high Hb levels matter............................................................8
Benefits of high haemoglobin level . .............................................9
Is your pig at risk of an iron gap?................................................10
Benefits of second iron injection.................................................. 11
Iron Deficiency Anaemia Detection and Treatment
How do you know if a piglet is suffering from anaemia?............. 12
How iron treatment sources differ................................................13
The benefits of injection and technique..................................14-15
Every drop counts.......................................................................16
When and how to select pigs for evaluating herd level anaemia....... 17
How to test your selected pigs....................................................18
Blood test for diagnosing anaemia (pen-side and lab)...........19-20
Other Anaemia Contributors and Conditions
What if my pigs get infected with a virus?...................................21
About vitamin E deficiency and mycotoxins in feed?.............22-23
Resources and References
Uniferon benefits........................................................................24
Iron expert board.........................................................................25
Pharmacovigilant anaemia care..................................................26
The basics of adverse events in parenteral Iron......................... 27
Resources and references.....................................................28-29
Contacts......................................................................................30

About this handbook


This pen-side resource tool enables the modern swine operation
to evaluate and improve their production with basics in the iron
status of the piglets. Helpful diagnostic and treatment protocols are
presented as a convenient resource to ensuring best practices.
What you will find on the following pages:
Information on our F.A.C.T iron deficiency anaemia
assessment program
How and why pigs become iron deficient
Industry-accepted iron level standards
How to clinically assess a herd
Effective iron treatment program and administration
Best practices

About Pharmacosmos
Pharmacosmos is the leading manufacturer and developer of
prevention and treatment of iron deficiency anaemia in humans
and animals. Our Uniferon (Iron(III) Dextran) is the only prevention
and treatment of piglet anaemia approved by health authorities in
Europe, Asia and by FDA in the US.
Uniferon is manufactured according to highest quality in our
manufacturing facilities in Denmark. Pharmacosmos works closely
with pig breeders, veterinarians and partners around the world to incorporate best practice solutions into our treatments - and Uniferon
is a simple way to realize higher production yields and higher profits.
Learn more about Pharmacosmos, the leading treatment and
prevention of iron deficiency anaemia in piglets.
Learn more - visit www.pharmacosmos.com

About Uniferon
Uniferon from Pharmacosmos is an iron supplement for piglets
containing 200 mg iron per ml. Uniferon promotes better health and
faster growth.
It is well known that iron supplementation of pigs on day 3 post
farrowing has been the industry standard for addressing iron
deficiency anaemia through injection of 200 mg iron.
Uniferon is the only world wide brand for preventing and treatment
of iron deficiency anaemia, and:
Ensure high haemoglobin levels1
Helps ensure optimal average daily gain (ADG)1
Promotes higher growth post weaning1,3
Completely absorbed with a high safety profile7
Global approval
Only high dose (200 mg/ml) FDA approved iron product in US8

What is the F.A.C.T program?


Our F.A.C.T program has been designed to provide a 360 view
of the iron status of piglets on the modern swine operation.
In close cooperation with production managers and farm
veterinarians, the F.A.C.T program:
P
 rovides a holistic view on the production facility on factors
impacting iron status in piglets
Introduces a convenient pen-side test for iron deficiency anaemia
Provides accurate and convenient identification of the iron
deficiency anaemia status of piglets and the herd
Eliminates guesswork and risk of misdiagnosis
Aspires toward an industry best practice
Provides the knowledge resources for the industry

F.A.C.T
The acronym F.A.C.T stands for

Farm Anaemia Certification and Training


Enrolling in F.A.C.T is easy by visiting
www.uniferon.com

What are the F.A.C.T benefits?


F.A.C.T has benefits for farmers and provides access to a large data
base of information and the support to begin making a significant difference in your herd. Do not leave your piglets at risk of misdiagnosis.
Be certain about your herds iron status, implement F.A.C.T today.
Our F.A.C.T program features three key features:
Assessment
Accurate haemoglobin pen-side measurements
Clinical results in 30 seconds
Tools for getting started
Training
Education on role of iron in physiology
Calculating iron requirements of individual piglets
Piglet handling
Iron administration/injection techniques
Field training for staff, advisors and consultants
Overview
360 view of welfare and health status of piglets
Access to research reports
Conducting trials and studies as necessary

Why high Hb levels matter


Anaemia is a condition with lack of iron-carrying haemoglobin in the
red blood cells. It typically occurs when the piglets iron stores are
depleted or when the exposure to stress conditions either inhibits
the build-up of haemoglobin or increases the degradation of
haemoglobin in the piglet. Iron deficiency is either a sub-clinical or
clinical manifest of anaemia.
Haemoglobin is a critical protein that enables red blood cells
to carry oxygen throughout the body. Haemoglobin along with
myoglobin, are proteins that require adequate levels of iron to
maximize growth and support immune system development.
Clinical benchmarks for optimal Hb levels and the relationship to
piglet anaemia status are:
<90 = Clinical anaemia
90-110 = Subclinical
>110 = Optimal
For optimal pig health
and performance,
haemoglobin level must
be at or above 110 g/l2

Benefits of high haemoglobin level


Elevated haemoglobin levels are important as these are known to
further benefit oxygen transport, immune function, vitality and
metabolism in piglets. A recent study has shown remarkable
associations of the haematological status at weaning and the weight
gain post-weaning and it is believed that optimized post weaning
growth requires haemoglobin levels above 110 g/l2.
It has been demonstrated that increasing levels of Hb were
positively associated to growth rate of piglets post-weaning
(p=0.0003, estimate=1.8 g ADG/gHb/l). Thus, a variation of 10 g/l
in haemoglobin at weaning results in a variation of 18 g/day in
weight gain 3 weeks after weaning3.

Estimated ADG (g/day)

300
250
200
150
100
50
0
70

80

90

100

110

Hb

120

130

140

150

Each time the pre-weaning haemoglobin level is increased with


10 g/l the weight gain post-weaning increases with 18 g/day3.
9

Is your pig at risk of an iron gap?

300

200 mg administration (day 1-3)

250
200
150

-100
-150
-200
-250

Iron consumption in
relation to growth

50

24

98

8,

72

46

8,

7,

20

7,

94

69

7,

7,

43

6,

17

91

6,

6,

6,

39

5,

13

Point where iron


requirements
exceed availability

5,

87

61

5,

35

5,

4,

09

83

4,

4,

57

4,

31

06

3,

3,

80

3,

54

28

3,

2,

02

2,

76

2,

2,

1,

0
-50

50

50

65

Second administration
(before day 17)

100

1,

Hypothetical
model for
Iron Gap5

Fe 3+ reserve (mg)

Improved weight gains on an all-milk ration increase the risk of the


developing iron deficiency and, hence, may well prevent optimal
weight gains as well. This increased productivity can contribute to a
potential iron gap due to the depletion of iron stores from birth and
low levels of iron in the sows milk (approx. 1 ml/daily intake) which
are diminished to even lower levels due to increased litter sizes.4

Iron Gap

Kg body weight (kg)

One 200 mg dose of iron day 1-3 after birth accommodates


approximately 4 kg of gain. An additional 200 mg dose at about
day 14 is recommended to help meet growth demands for the
next 4 kg.5
Calculate piglet iron requirement to avoid iron gap
Visit fact.uniferon.com for a convenient calculator to help
with assessments.

10

Benefits of second iron injection


One 200 mg dose of iron day 1-3 after birth accommodates
approximately 4 kg of gain. An additional 200 mg dose at about
day 14 is recommended to help meet further growth demands.
Recent trial data revealed significant increases in weight gain and
haemoglobin levels in pigs when treated with a second 200 mg/ml
dose over pigs provided only a single dose.1

325

306
2 injections of Uniferon
1 injection of Uniferon

Day 34-50
(post weaning)

Haemoglobin (g/l)

Weight gain (g/d)

Effect of second Uniferon injection

123

113

Day 34
(at weaning)

(Weight gain and Haemoglobin results show statistical significance


of p=0.01* and p=0.0001*** respectively.)

Administration of a second dose of iron prior to weaning has shown


benefits in growth rates and overall performance especially in pigs
exceeding 4 kg of growth after birth.1, 6

11

How do you know if a piglet is


suffering from anaemia?
Early iron deficiency often goes unnoticed since it is difficult to detect until severe. Therefore, testing haemoglobin levels is the most
practical and conclusive sign of anaemia detection.
Pen-side or laboratory evaluation of the haemoglobin level in a
blood sample taken from a vein will show whether the pig suffers
from iron deficiency anaemia.
First signs of anaemia:
Poor growth
Paleness of the mucous membranes
Severe signs of anaemia:
Listlessness (piglets slow to move, tired, remain lying)
Rough hair coat and wrinkled skin
Labored breathing (ex. piglets out of breath during weaning day
movement to transport truck)
Increased heart rate
Increased respiratory rate or spasmodic movement of the
diaphragm muscles following exercise (ex. piglets gasping for
air when walking, especially when walking to transport truck)
Once visual signs of anaemia appear, growth rates have already
been negatively affected.
12

How iron treatment sources differ


Colostrum and milk from the sow are both good sources of iron
however the iron concentration levels are inadequate. Therefore,
iron supplementation is required.
Iron from the sow
Swabbing the sows udder with an iron-rich solution is an option
but is typically too labor intensive to be an effective long-term
option.4
Iron from the environment
Piglets on commercial swine operations have no or little access to
natural soil habitat in which innate rooting behaviors would provide
a source of iron and other minerals.4
Parenteral iron supplementation
Widely recognized as the most accurate and effective treatment
solution due to precision.4
Oral supplementation
The challenge for orally administered iron treatments (whether
paste, pill or liquid) is inefficient absorption of iron from the gut,
especially in the immature gut of piglets. Furthermore, when iron
is only available orally there is no assurance that an equal or
adequate dose will be available for the individual piglet.4

13

The benefits of injection


Parenteral administration
The most precise and assured method of administering iron is
through injection. With proper technique this dosing protocol offers
the following advantages:4
Precise dosing
Maximum efficacy
Cost-efficient workflow with dose shortly after birth
Minimized risk of iron deficiency anaemia
Supports optimal growth rates on an all-milk diet
Increased general health
Administering a single
200 mg dose of iron
to all piglets shortly
after birth can begin
addressing anaemia
from the low iron levels
available at birth.

14

Injection technique
For successful anaemia care, it is important to practice correct
injection technique. This is necessary in order to ensure that
the iron is dosed correctly and that the iron medication enters
effectively via the tissue. Otherwise you will likely experience
anaemia in the pig. Ensure that all involved persons are aware of
the proper injection techniques to help ensure optimal iron care.
1. Choose injection site.
Parenteral administration
can be either intramuscular
or subcutaneously and the
approved/recommended site
can vary by country:
Intramuscular:
Hold the piglets body towards
you. Injection should be
intramuscular in the neck
2.5 - 5 cm behind the ear.
Subcutaneously:
Hold the piglet in its hind
legs, so it hangs head down
with its abdomen facing
you. Injection should be
subcutaneously in the
inguinal skin fold.
2. Check that the injection
site is clean and dry. If the
piglets skin is dirty or wet,

wipe it clean with cotton wool


soaked in surgical spirit. Allow
the skin to dry before injection
3. Use a small needle, 20
gauge 15 mm that has been
sterilized
4. Pull skin slightly forward
before inserting the needle
5. Quickly and firmly insert
the needle
6. Release the skin, give the
injection, and remove the
needle. The skin then springs
back in place, covers the hole
in the muscle and seals the
injected material in place,
minimizing the risk of leakage
7. Change needles after every
ten piglets or after each litter.
15

Every drop counts


A high degree of concentration and treatment discipline separates
success from failure in the delivery of correct amount of iron.
Pharmacists generally consider 1 drop equivalent
to 0.05 ml, which means that 1 ml makes up 20
drops. With a 200 mg/ml product each 0.05 ml
drop contains 10 mg iron. If 4 drops fail to be
injected this corresponds to approximately 40 mg
less iron available and the piglet would get only
160 mg of iron and remains at risk of anaemia.
In low dose applications such as when 100 mg/ml is being
administered several challenges can occur including:
Insufficient iron to meet requirements without multiple injections
Increased backflow and leakage with multiple injections - often
causing greater losses of 8-10 drops and still leaving the piglet
short of iron requirements
Increased risk of muscle trauma
Greater risk of injury and undue stress
Losing just 1 drop of Uniferon, means losing 10 mg of iron and
the pig remains at risk of anaemia.

16

When and how to select pigs for


evaluating herd level anaemia
Iron supplementation regimes for piglets are most often very
standardized with little focus on variations in birth weight, growth
rate or weaning age in individual herds.
When to test pigs
A critical time for iron deficiency anaemia development is
immediately before weaning, when the iron stores from the initial
dosing has been depleted and the uptake through feed is still of
minor importance.
How to select pigs
To establish an overall prevalence of anaemia within a herd, blood
samples should be taken from random piglets in random litters
within the oldest batch of piglets in the farrowing unit.
In a herd with 5% of animals suffering from anaemia (<90 g Hb/l)
a sample size of 20 animals is sufficient to determine the
prevalence with an allowable error of +/- 10 %.

17

How to test your selected pigs


To determine the prevalence of anaemia and iron deficiency
within the herd, a haematological examination is needed.
Haematological examinations can be done by handheld
photometer or a reference laboratory.
Method 1 - pen-side testing using Hb photometer:
A single drop of blood is taken from the ear vein with a simple
pin prick. The blood is introduced into a disposable cuvette by
capillarity and then placed in the Hb photometer. Results for
haemoglobin concentration are obtained in less than a minute.
Method 2 - lab testing using vacutainer tube:
Take approximately a 3 ml blood sample by puncture of vena cava
or the jugular vein using an EDTA stabilized vacutainer tube.
Cool the samples immediately after termination of sampling.
Testing for haemoglobin concentration at a reference lab should
be carried out as soon as possible and preferably no later than the
following day.

18

Pen-side blood test for


diagnosing anaemia
Measuring the haemoglobin with the handheld device HemoCue
201+ Hb photometer is a fast and reliable way to determine the
prevalence of anaemia and iron deficiency within the herd.9
Blood sampling for pen-side testing using HemoCue 201+:
The HemoCue 201+ Hb photometer is technically and
economically well suited for pen side haemoglobin examination.
1. A single drop of blood is taken
from the ear vein by puncturing
the vein

2. The blood is introduced into


a disposable cuvette

3. P
 lace the cuvette in the
HemoCue 201+ Hb photometer

4. R
 esults for haemoglobin concentration
are obtained in less than a minute

19

Blood test in lab for


diagnosing anaemia
If blood samples are drawn by puncture of vena cava or the jugular vein, extended analysis can be carried out.
Take approx. 3 ml in EDTA stabilized and plain vacutainer
tubes and cool blood samples in refrigerator immediately after
termination of sampling. Testing at a reference lab is carried out as
soon as possible and preferably no later than the following day.
Tests

Significance

Notes

Blood
Measures amount of Hb in blood Blood Hb may be
normal in initial stages
haemoglobin
Value <90 g/l suggestive of
of IDA
severe IDA
Value <110 g/l suggestive of IDA
RBC count

Quantifies red blood cells


in blood
Value <6.4-8.4 x 1012 /l
suggestive of IDA

Hematocrit

Measures volume % of RBC


in blood
Value <0.26 - 0.41 l/l is
suggestive of IDA

TIBC

Measures bloods capacity to


bind iron with transferrin

Normal count of RBCs


with low Hb content
may be predominant
in IDA
Due to slow turn over
(62 days) of RBC, initial
iron deficiency may be
missed
Better indicator of IDA
than Hb measurement
in piglets
Indicates % of iron
bound

Value 104-188 mmol/l


is suggestive of IDA
20

What if my pigs get infected


with a virus?
In many herds the presence of a viral infection such as porcine
reproductive and respiratory syndrome (PRRS) or porcine circovirus type 2 (PCV2) often means the pigs are also anemic, due to
immunosuppression in spite of appropriate iron supplementation.
Trial results show significant better mean weight gain and
haemoglobin levels in viremic pigs treated with two 200 mg doses
versus the placebo pigs treated with only one 200 mg dose.6
Effect of a second Uniferon injection in immunosuppressed pigs

Weight gain (g/d)

473

2nd Uniferon injection


Saline injection

6.38

Haemoglobin (mmol/l)

6.62

523

Day 12-32

Day 12-32

(Weight gain and Haemoglobin results show statistical significance p=0.01*)

Piglets are often anemic due to viral infection


Optimal iron supplementation ensures improved haemoglobin
levels, which are a prerequisite for a strong immune system
It may be advantageous to give further iron treatment to
immunosuppressed pigs

21

What about vitamin E deficiency?


There are various conditions which can cause iron absorption in
pigs to be reduced. One of them is vitamin E deficiency induced
anaemia.
As the sow is determinant for the piglets vitamin E level, the sows
vitamin E status is also of importance for optimal anaemia care.
A sows ability to absorb and transfer vitamin E to the milk varies
greatly from sow to sow. Variation in vitamin E uptake is also seen
among piglets, and may even vary within the same litter.
If the sows are vitamin E deficient this approach is
recommended:

Analyze/control feeds content of vitamin E

Make sure that gestation mixture contains min. 80 mg


vitamin E / Fes and lactation diet min. 92 mg vitamin E / Fes

Synthetic vitamin E (acetate bound) may be added with up


to 250 mg/sow

If the piglets are vitamin E deficient this approach is


recommended:

Provide natural vitamin E (peroral administration) to each
piglet. It is recommended to use natural vitamin E for
improved bioavailability

22

What about mycotoxins in feed?


There are various conditions which can cause iron absorption in pigs
to be reduced. One of them is mycotoxins induced anaemia.
Mycotoxins in feed
Mycotoxins in swine feed is a well-known problem all over the world;
however, more prevalent some places than others. Especially in
humid climates problems with fusarium toxins in the crops may
occur, which causes a strain on the animals and leads to potential
anaemia.
The reason for this is that mycotoxins weaken the immune system
and inhibit the bone marrow as well as the vital organs. This causes
the pigs to reduce their production of red blood cells and leads to
anaemia.
Mycotoxins in swine feed not only weaken the immune system of
the pigs; it may also cause loss of vitamin E in the feed. As vitamin
E is essential for the uptake of iron in both sows and piglets it further
enhances the mycotoxins induced anaemia.
It is recommended to solve the mycotoxins problem by tracing the
sources of toxins and eliminate/inhibit these. This can be done
with toxin binders.

23

Uniferon benefits
Uniferon 200 mg/ml parenteral iron injection has proven beneficial
for preventing iron deficiency anaemia
Uniferon 200 mg/ml is research-proven to boost haemoglobin
levels and average daily gain
Uniferon is the only iron supplement supported by research
trials worldwide
Uniferon adheres to the highest standards of quality, safety and
efficacy, and has approval in Europe, Asia and North America
(including FDA approval in the United States)
#1 iron supplement in the world

24

Iron Expert Board


Pharmacosmos has established the Iron Expert Board (IEB) with
a dedicated panel group consisting of international Key Opinion
Leaders, representing some of the best minds in the field of pig
health and iron supplementation.
The goal of the IEB is:
To ensure adequate iron supplementation for all piglets
- avoiding the iron gap
To widen the understanding of anaemia and the relation between
anaemia and growth in particular
To avoid inappropriate use of iron and iron overload
To make up-to-date recommendations for iron supplementation
in order to prevent anaemia

25

Pharmacovigilant anaemia care


Each national health care system has a pharmacovigilance system
associated with the prescription and administration of medicines
in humans and animals, which ensures a satisfactory handling of
adverse events in compliance with local laws and guidelines.
Pharmacosmos has the overall responsibility for maintaining a
highly compliant and skilled safety surveillance of Uniferon.
Pharmacosmos has organized worldwide reporting of adverse
events via Uniferon partners and in compliance with local
legislation. In parallel, Pharmacosmos systematically reviews the
worldwide scientific literature for the product and is responsible for
signal detection.
Comparison over time of the ratio of animals reported for adverse events/
lack of efficacy (ABON, including 01)7
Ratio (number of
animals/number of doses)

0.0002%

0.00003%

Periodic Safety Update Report (PSUR)


Product: Veterinary iron dextran, solution for injection
Period of reporting: 01.08.2009 31.07.2012

26

The basics of adverse events in


parenteral iron
Intramuscular injections of parenteral irons in general may
cause transient discoloration/calcifications at the injection site
or hypersensitivity reactions normally considered non-serious
adverse events.10
Intramuscular injections of parenteral irons can very rarely cause
a serious adverse event (deaths).
The most likely reason for a serious adverse event following the
administration of parenteral iron is:10
Exposure to an intravenous injection
Iron shock associated with genetic factors; vitamin E and/or
selenium deficiency
Contamination with Clostridia bacteria due to improper handling/
storage conditions
The Active Pharmaceutical Ingredient (API) from Pharmacosmos
is produced in batches each of a volume equivalent to approximately 6 million doses Uniferon. In the event of an adverse event,
the elimination of any likelihood of production related failure is
of high concern to Pharmacosmos. Several scenarios could be
expected. Maximum care and caution have been exercised in
product manufacturing to achieve European MRP10 approval and
FDA approval in the US.8

27

Resources
To learn more about Uniferon and Iron Deficiency Anaemia
please visit:
uniferon.com
Determine the potential mean iron need within a litter with our online
Iron/Weight Gain Optimizer (I/WGO):
uniferon.com/iwgo
Determine the investment advantage of iron supplementation for
your operation with our online F.A.C.T Calculator:
fact.uniferon.com

28

References
1

H
 augegaard, J. et al., 2008: Effect of supplementing fast-growing,
late-weaned piglets twice with 200 mg iron dextran intramuscularly
The Pig Journal (2008) 61, 69 73

N
 ielsen, J.P. et al., 2013: Herd diagnosis of iron deficiency in piglets.
In: Proc. 5th ESPHM Cong., May 2013

N
 ielsen, J.P. & S. Bhattarai 2014: Association of haematological status
at weaning and weight gain post-weaning in piglets.
In: Proc. 23rd IPVS Cong., June 2014

4  Herschel, H.J. et al., 2012: A review of recent supplemental iron industry


practices and current usage of uniferon (iron dextran complex injection,
200 mg/ml) in baby pigs. In: Proc. 43th AASV Cong., March 2012
5  Van Gorp, S. et al., 2012: Preventing iron deficiency by avoiding an iron
gap in modern pig production. In: Proc. 43th AASV Cong., March 2012
6

B
 ach, J. et al., 2006: Effect of an additional iron injection in a PMWS
positive herd in respect to hematocrit, haemoglobin and growth rate.
In: Proc. 19th IPVS Cong., June 2006

P
 eriodic Safety Update Report (PSUR); Product: Veterinary iron dextran,
solution for injection; Period of reporting: 01.08.2009 31.07.2012

8  ANADA 200-256 Iron Dextran Injection-200 (NADA # 134-708)


9

h
 ttp://www.hemocue.com/

10 Procedure No. DK/V/0114/01/MR

29

Contacts
Pharmacosmos Corporate Headquarters:
Pharmacosmos A/S
Roervangsvej 30
DK-4300 Holbaek
Denmark
T: +45 59 48 59 59
F: +45 59 48 59 60
E: uniferon@pharmacosmos.com
If you have any questions, or want to share your thoughts or
advice, we would like to hear from you.
For a complete global Uniferon partners please visit:
uniferon.com

30

T: +45 59 48 59 59
E: uniferon@pharmacosmos.com

V2015-03 v 1.0

#1 iron supplement in the world

T: +45 59 48 59 59
E: uniferon@pharmacosmos.com

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