BLOOD DONORS AND BLOOD COLLECTION
Handling low hemoglobin and iron deficiency in a blood donor
population: 2 years’ experience
Karin Magnussen1 and Steen Ladelund2
BACKGROUND: Iron deficiency and blood donors with
low hemoglobin (Hb) concentration are well-known
challenges in any blood bank setting. In the Capital
Region of Denmark, a new approach was adopted that
centralized measurement of Hb, initiated ferritin (F)
measurement, and established a center for donor Hb and
iron. An algorithm was created based on Hb and F levels,
which drove decisions on outreach by the donor Hb and
iron resource team to the donor, including whether to
provide iron supplementation or, on rare occasions, a
referral to the donor’s general practitioner.
STUDY DESIGN AND METHODS: The change in Hb
for repeat donors was followed during the first 2 years of
the intervention strategy, which included measurements
of F and offering intermittent iron supplementation to
some of the donors.
RESULTS: In 2 years, 62,663 blood donors donated
193,288 units of blood and 318 donors gave 754 complete
blood count blood samples. Over time in the repeat
donors, the Hb increased from 15.39 to 15.60 g/dL and
13.85 to 14.06 g/dL in male and female donors,
respectively, and the proportion of donors with low Hb
decreased from 0.9% to 0.3% and 3.9% to 2.7% for the
male and female donors, respectively.
CONCLUSION: The program with goal-directed iron
supplementation only to those that would benefit has led
to an increase in Hb concentration and a reduction in the
proportion of donors with low Hb concentration.
I
ron deficiency and blood donors with low hemoglo-
bin (Hb) concentration are well-known challenges in
any blood bank setting. In the Capital region of Den-
mark, a new approach was adopted that centralized
measurement of Hb, initiated ferritin (F) measurement,
and established a center for donor Hb and iron. An algo-
rithm was created based on Hb and F levels, which drove
decisions on outreach by the donor Hb and iron resource
team to the donor, including whether to provide iron sup-
plementation or, on rare occasions, a referral to the
donor’s general practitioner (GP).
We present the results of the first 2 years of our inter-
vention strategy, aimed at reducing iron deficiency and
specifically at reducing the proportion of donors with a
low Hb concentration (<12.5 and 13.5 g/dL in women
and men, respectively) caused by iron deficiency. Since
February 1, 2012, we have had automatic transfer of
hematology and F results to our donor information tech-
nology (IT) system, which enables us to assess the effect
on Hb of our intervention.
MATERIALS AND METHODS
To run the program were six technicians who after special
training, as part of their job, together with one doctor
formed the donor Hb and iron resource team. Monday to
ABBREVIATIONS: CBC 5 complete blood count; F 5
ferritin; GP 5 general practitioner; IT 5 information
technology.
From the 1Department of Clinical Immunology and Blood
Centre, Copenhagen University Hospital, Rigshospitalet,
Copenhagen, Denmark; and the 2Clinical Research Centre,
Copenhagen University Hospital, Hvidovre, Denmark.
Address reprint requests to: Karin Magnussen, Blood Centre
Lab, sec 231, Hvidovre Hospital, 2650 Hvidovre, Denmark;
e-mail: karin.magnussen@regionh.dk.
Received for publication November 1, 2014; revision
received March 29, 2015; and accepted April 1, 2015.
doi:10.1111/trf.13152
C 2015 AABB
V
TRANSFUSION 2015;55;2473–2478
Volume 55, October 2015 TRANSFUSION 2473
MAGNUSSEN AND LADELUND
Fig. 1. Flow chart of the Hb- and F-based algorithm.
Friday on average 1.5 technicians were working with the
program. They lifted the responsibility from the donation
sites and took care of questions related to Hb and F. To
guide the team, an algorithm that takes Hb and F into
account was used (Fig. 1).
From February 1, 2012, to February 1, 2014, a total of
62,663 blood donors (52% women and 48% men) donated
193,288 units of blood and 318 donors gave 754 complete
blood count (CBC) blood samples in our blood centers in
the Capital Regional Blood Center. In the calculations of
Hb and low Hb, the results from the first-time donors
were removed and only the results from 184,075 dona-
tions from repeat donors were used. The Hb limit for don-
ation was 12.5 g/dL for female and 13.5 g/dL for male
donors, but Hb was routinely determined after donation
for most donors. Donors were allowed four donations/
year. The volume donated was 450 mL and approximately
40 mL for samples. Before donation the interviewer
checked the Hb measurements from previous donations,
and if they were above 12.5 or 13.5 g/dL for female and
male donors, respectively, the donor was allowed to
donate. If a previous Hb was below the donation limit, a
predonation Hb was taken and analyzed immediately on
a hematology analyzer (pocH-100i, Sysmex, Ballerup,
Denmark), and then the donor was only allowed to donate
if the current Hb was above the limit. Hb was measured
on a venous sample secured from the presample pouch,
which is an integral part of the quadruple blood pack with
2474 TRANSFUSION Volume 55, October 2015
in-line RCC soft housing filter, from Fresenius Kabi TT
(Copenhagen, Denmark). When only samples were taken,
it would also be venous samples. The Hb samples were
sent from the blood collection sites to the center for donor
Hb and iron where they were analyzed as part of a CBC
on a hematology analyzer (D2100-XE, Sysmex) within 30
minutes to 24 hours. On the hematology analyzer together
with Hb, was measured hematocrit (Hct), mean cellular
Hb, mean cellular Hb concentration, mean cellular vol-
ume (MCV), red blood cell (RBC) count, platelet (PLT)
count, random deviation with-CV, random deviation with-
SD, and white blood cell (WBC) count. F concentration
was measured on the sample also used for analyzing viral
markers and the instrument used was an immunodiag-
nostic system (Vitros 3600 or 5600, Ortho Clinical Diag-
nostics Scandinavia, Sollentuna, Sweden). Hb and F were
measured both on donors that donate a unit of blood and
on donors where because of previous low Hb or clinical
suspicion of low Hb (e.g., if the donor had pale skin or if
the donor expresses fatigue, dizziness, or shortness of
breath), only blood samples were taken. The interviewers
and phlebotomists were trained to look for symptoms of
anemia, but they were only probed for, if the donor looked
anemic or volunteered symptoms. The results were auto-
matically transferred to the donor IT system (Blodflo € det),
and daily lists were produced, according to the algorithm
(Fig. 1). On the lists were donors who needed attention
from the donor Hb and iron resource team, that is, donors

with Hb or F concentrations outside what we had defined
as desirable for blood donors, namely, Hb of less than
12.5 g/dL for female donors, Hb of less than 13.5 g/dL for
male donors, or F of less than 60 mg/L for either sex. The
World Health Organization definition of iron deficiency in
adults is 15 mg/L and a F level of 30 mg/L corresponds to
215 mg of iron stores,1 which is what is lost when a person
with Hb 12.5 g/dL donates 490 mL. Also, with 3-month
donation intervals, the F will be 35% lower at the next
donation.2 Based on this we decided to offer iron supple-
mentation to donors when the F level was below 60 mg/L.
We also routinely examined donors with high Hb3 or F or
abnormal values for Hct, PLTs, or WBCs, but this falls out-
side the scope of this article.
While Hb was assessed at every donation, F was not
due to economic constraints. F was measured at the first
donation and subsequently at every 10th donation4 or
more frequently if, for example, the Hb or F at the last
donation was low or high. In summer 2013 we assessed
the effect and saw that the program was not always suffi-
cient to maintain Hb above the donation limit. Therefore,
we began repeat testing of F in the donors that were
handled by the donor Hb and iron resource team, and the
increase in measurements of F took effect from August
2013. Thus, other than at the first donation, measurement
of F was often not routine but was dependent on prior
results. This means that any change in iron deficiency
cannot be measured directly with change in F, but only
indirectly with possible changes in Hb.
For the donors with a Hb higher than the donation
limit, the aim was to maintain the Hb higher than the
donation limit, by offering iron supplementation to
donors with F of not more than 60 mg/L. Regarding the
donors with Hb of less than the donation limit, some will
have a Hb below the donation limit because of low iron
stores; for some it is their normal Hb and for a few Hb is
low because of disease. To avoid disturbing and worrying
all the donors with low Hb, by referring to the GP, we
looked individually at the low Hb donors with F of less
than 40 mg/L and based on a phone call, the donor history,
and the CBC it was decided whether to send iron supple-
mentation or to refer the donor to the GP. The donors with
F of higher than 40 mg/L were always referred to the GP.
Iron supplementation is known to cause abdominal dis-
comfort, which is why we have two different kinds of iron
tablets. The iron tablets that were offered to the donors
were Jern C (330 mg ferrous fumarate [100 mg of iron]
and 60 mg of ascorbic acid) from Medic Team A/S
(Allerød, Denmark); price $1.60/20 tablets, this was the
first choice to give the donors, due to the slightly lower
costs. If the donor complained of side effects, AminoJern
(ferrous bisglycinate 25 mg iron) from Pharmovital (Char-
lottenlund, Denmark); price $1.67/20 tablets was offered.
We recommended that the donors take one tablet at bed-
time with water, to avoid interaction with food or drinks.
LOW HEMOGLOBIN AND IRON DEFICIENCY
If side effects occurred with both kinds of tablets, we rec-
ommended that they took one tablet of the donor’s choice
every second or third day. The iron leaflet was always sent
together with iron tablets and was also available at the
blood collection sites. To improve compliance, the donors
were contacted by phone when sending 100 iron tablets
or if there seemed to be no or insufficient effect of previ-
ous sent iron supplementation.
Statistical analysis
Raw data are presented as counts and percentages or
mean values and standard deviations as appropriate.
Time trends were modeled with study time in two seg-
ments, one starting at the time of the first donation and a
second one starting in August 2013. These two time seg-
ments form the basis for modeling changes over time in
two linear, but continuous, stages according to algorithm
change. The models used for continuous endpoints for,
for example, Hb, are mixed linear regression with random
intercepts and slopes to account for correlation between
measurements within individuals. For the binary outcome
a logistic marginal regression was used, applying an
unstructured correlation matrix. Data management, illus-
trations, and analysis were performed in R.5 p values less
than 5% were considered significant.
RESULTS
The donation frequency was 1.54/year (1.4 for the women
and 1.7 for the men).
Hb
Over time from February 1, 2012, to February 1, 2014, the
Hb increased significantly for both repeat female
(p < 0.0001) and male donors (p < 0.0001). And even sig-
nificantly more since August 2013 (p < 0.0001), after
measurements of F on indication was increased, leading
to an increase in iron supplementation for both female
and male donors (Fig. 2). The increase in Hb for the
male donors from February 2012 to August 2013 was
0.0033 g/dL/month and from August 2013 to February
2014 the increase was 0.0333 g/dL/month. For the female
donors from February 2012 to August 2013 the increase
was 0.0059 g/dL/month and from August 2013 to Febru-
ary 2014 the increase was 0.0257 g/dL/month. The mean
Hb for the first 3 months was 15.39 g/dL for the male
donors and 13.85 g/dL for the female donors and in the
last 3 months the Hb for the male donor was 15.60 and
14.06 g/dL for the female donors. The fraction of donors
with low Hb decreased over time from 0.9% in the first 3
months to 0.3% in the last 3 months for the male donors
and from 3.9% to 2.7% for the female donors. The
decrease in percentage of donors with low Hb was signif-
icant for both female donors (odds ratio [OR]/
Volume 55, October 2015 TRANSFUSION 2475
MAGNUSSEN AND LADELUND
Fig. 2. Hb by sex and month. Mean of Hb in repeat donors.
month 5 0.97; p < 0.0001) and male donors (OR/month-
5 0.97; p < 0.0001; Fig. 3).
F within 10 donations, a large number of tests were per-
The minimum donation interval was 90 days, so the F
measured during the first 3 months could be considered
as a baseline. In the first 3 months, for the male donors
median F was 63 mg/L (interquartile range [IQR], 40-99),
13% were less than 30 mg/L and 1.5% less than 15 mg/L. In
all 47% of the male donors who donated during the first 3
months were offered iron supplementation. For the
female donors median F was 34 mg/L (IQR, 22-52), 43%
Fig. 3. Low Hb by sex and month. Percentage of donations
and blood samples with Hb below 12.5 and 13.5 g/dL for
female and male repeat donors, respectively.
2476 TRANSFUSION Volume 55, October 2015
Fig. 4. F measurements by sex and month.
were less than 30 mg/L and 11% less than 15 mg/L. In all
82% of the female donors who donated during the first 3
months were offered iron supplementation. Because F
was tested in all donors, where F had not been tested
formed in the first months of the program. Over time the
fraction of tests done on first-time donors and tests done
on indication would increase, as more of the regular
donors were tested (Fig. 4).
In Fig. 5 is shown the percent of donations that was
handled by the donor Hb and iron resource team. If com-
paring Figs. 4 and 5 it is seen that the percentage of
donors with treatment indicated was always higher in
female donors compared with male donors. It was corre-
lated with the number of F measurements, which may not
have been the case if F had been measured at all
donations.
We had with our IT system no way of counting the
number of donors that we recommended to see the GP,
and even though we encourage the donors to call us back,
not all did. Of those that did inform us, a part was not ill
and habitually had low Hb without being anemic, but four
were diagnosed with leukemia, two with bowel cancer,
and one with systemic lupus erythematosus. Another 11
informed their local blood bank and were permanently
deferred as unspecified disease. Among donors with low
MCV not explained by iron deficiency 23 were diagnosed
with heterozygous a or b thalassemia, one heterozygous
for HbS, and one heterozygous for HbE.
DISCUSSION
Iron deficiency and low Hb concentration is a problem
in all blood centers and can be found among all

Fig. 5. Percentage with F of less than 60 mg/L and/or low Hb
by sex and month. Percentage of donations and blood sam-
ples, with F of less than 60 mg/L and/or Hb of less than 12.5
and 13.5 g/dL for female and male donors, respectively, and
therefore had the attention of the donor Hb and iron
resource team.
groups of whole blood donors, but is most often seen
in frequent donors and female donors and is also
dependent on the genetic makeup of the individual
donor.4,6-11
The rate of erythropoiesis is dependent on iron avail-
ability, and furthermore iron deficiency reduces the
responsiveness of erythroid progenitors to erythropoie-
tin;12 therefore, iron-deficient blood donors will take lon-
ger to replace the RBCs lost by donation. Also iron
deficiency is associated with decreased physical endur-
ance capacity,13 fatigue,14 and impaired cognitive func-
tions15,16 and, not the least, fertile female donors risk
being iron-deficient already at the beginning of preg-
nancy, with increased risk of preterm delivery and low
birthweight of their newborn.17
In blood donors low Hb is more often than not due to
iron deficiency; however, in apparently healthy blood
donors it may also be a sign of disease. In a previous study
on 879 blood donors with low Hb, 1.7% were permanently
deferred due to disease, for example, cancer, cardiac dis-
ease, and cirrhosis.18 Delaney and colleagues19 found
1.9% of donors with disease among 104 anemic donors;
they suffered from leukemia and metastatic lung cancer,
and also in this study we found donors with low Hb that
were permanently deferred due to, for example, leukemia,
cancer of the colon, and systemic lupus erythematosus.
Many have recognized the problem with iron deficiency
and low Hb among blood donors and suggested longer
LOW HEMOGLOBIN AND IRON DEFICIENCY
donation intervals and/or iron supplementation to reduce
the problem.4,7-9,20
Based on previous experience and literature studies
and since our donation interval and volume were already
lower than what was used in the United States, we chose a
proactive approach with intermittent and graded iron
supplementation based on Hb and F. In the first 3 to 4
months there was a lot of work, with many F measure-
ments and many letters to be sent to donors with iron tab-
lets and information, but it has leveled off with around
30% of female donors and less than 5% of the male donors
needing attention. The proportion of donors in need of
attention will probably increase as the donors reach their
10th donation, but with the amount of prophylactic iron
supplementation offered to the donors, we do not expect
it to reach the level of the initial months. The systematic
and standardized approach has resulted in an overall
increase in Hb and a reduction in the proportion of
donors with low Hb, and we have avoided offering iron
supplementation to donors with hemochromatosis, dis-
ease, or habitual low Hb. The increase in Hb probably
reflects both the reduced proportion of donors with low
Hb and the fact that some donors previously have
donated with a Hb higher than the donation limit, but
due to iron deficiency lower than their habitual Hb, which
was later normalized with iron supplementation. Our
experience was that in donors with lower than their nor-
mal Hb due to iron deficiency, with the iron supplementa-
tion according to our algorithm, the Hb would easily
increase before the next donation, while it would take
considerably longer for the F to increase. A normal Hb
and reduced risk of iron deficiency are not only beneficial
for the donors’ well-being, but also for the patients
because a higher Hb in the donor means more Hb in the
RBC unit. Branda ~o and coworkers21 found impaired
deformability of iron-deficient RBCs, which could mean
additional negative influence on the quality of RBC prod-
ucts from iron-deficient donors compared with non–iron-
deficient donors. The program was possible to implement
with additional education to existing staff, and the price of
iron tablets and F measurements ($1.8/test) was probably
at least partly outweighed by the cost savings obtained by
centralizing the Hb measurements and the improved
quality for both donors and patients. The fact that F was
not measured at every donation is a limitation to the pro-
gram and a hindrance to show a possible development in
F. But even with the rare measurements of F, it did secure
that iron supplementation was only given to donors who
would benefit. In conclusion, the program with goal-
directed iron supplementation has led to an increase in
Hb and a reduction in the proportion of donors with low
Hb, and while the aim was to keep the donors within our
limit for Hb and F, the main benefit of the program was to
have a well-functioning program for when the donors did
fall outside anyway.
Volume 55, October 2015 TRANSFUSION 2477
MAGNUSSEN AND LADELUND
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