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Transfusion Medicine, 2010, 20, 22–29 doi: 10.1111/j.1365-3148.2009.00979.

ORIGINAL ARTICLE

Study of iron stores in regular plateletpheresis donors


E. A. Page,1 J. E. Coppock2 & J. F. Harrison3 1 National Blood Service, Tooting, London, UK, 2 Birmingham, UK,
and 3 Colindale, UK

Received 07 May 2009; accepted for publication 16 October 2009

summary. Plateletpheresis donors will lose up to intervals found to be iron depleted. The percentage of
100 mL of blood at each donation, leading to con- iron depleted male subjects decreased as donation inter-
cern that they may become iron deficient, particu- vals increased. Correlation with lifetime donations of
larly if donating at the maximum allowed frequency platelets was not demonstrated, although no donor who
under National Blood Service policy of every 2 weeks. had given fewer than 14 blood and/or platelet donations
The serum ferritin levels of 508 regular plateletphere- was found to be iron depleted. In males there was a
sis donors and 101 non-donors were measured to clear correlation between iron depletion and frequency
indicate the level of their iron stores. About 33·9% of donation. There appeared to be no correlation with
(156/460) of platelet donors had depleted iron stores lifetime number of platelet donations. As a result of this
compared with 3·1% (3/97) non-donors. Results for study, we have advised that volunteers should not donate
male and post-menopausal female donors were similar platelets more than 15 times per year, so that red cell
with 36·2% (131/362) of males and 37·7% (20/53) of loss is no more than the equivalent of three whole blood
donations (1500 mL).
post-menopausal females showing iron depletion. There
was clear correlation with donation frequency in males Key words: donation, iron stores, plateletpheresis donor,
with 63·9% (46/72) of males donating at 2 weekly serum ferritin.

At the time of this study in England and Wales, MATERIALS AND METHODS
plateletpheresis donors could donate at a minimum
Study design
interval of 2 weeks but no more than 24 times a year.
Blood loss within the harness (Gambro BCT, 2004) and The National Blood Service (NBS) collects platelets
at sampling on the Trima Accel cell separator is between by apheresis at 24 static sites. Donors were selected
80 and 100 mL resulting in an annual blood loss of to participate in this study from three of the largest
up to 2400 mL in someone donating at the maximum static sites – Brentwood, Birmingham and Tooting: 508
frequency. This is the equivalent of four to five whole (402 males, 106 females) platelet donors participated
blood donations per annum. in this study and 101 controls (46 males, 51 females).
In order to understand the effect of regular platelet- All of the platelet donors had previously donated whole
pheresis on donor iron stores, a three-centre study blood prior to joining the plateletpheresis programme
was conducted to determine whether regular platelet on which they donate platelets only and refrain from
donors become iron depleted. In addition, the rela- blood donation, and the control subjects had never
tionship between donor iron status and lifetime num- donated platelets or blood. Donors were selected in
ber of donations, donation frequency, gender and other two equally sized groups: 256 donors (203 males, 53
factors such as diet or pre-menopausal status was females) had donated platelets for more than 3 years
examined. and 252 donors (199 males, 53 females) had donated
for less than 3 years. Donors were selected at random
and reflected a range of donation frequencies from those
who donated at 2 weekly intervals to those who donated
Correspondence: Dr Elizabeth Anne Page, National Blood Service
NBS Tooting, 75 Cranmer Terrace, London, United Kingdom.
at 8 or even 12 weekly intervals. The iron stores of
Tel.: 0208 258 8300; Fax: 0208 258 8491; both participating donors and controls were assessed
e-mail: lizanne.page@nbs.nhs.uk by measuring serum ferritin, which is recognized as
© 2009 The Authors
22 Journal compilation © 2009 British Blood Transfusion Society
Iron stores in plateletpheresis donors 23

having a high degree of correlation with the amount of Equipment and assays
storage iron (Walters et al ., 1973) in healthy subjects.
Plateletpheresis was performed on the Trima Accel
Venous blood samples for serum ferritin and a full
Automated Blood Collection System, version 5·1
blood count were taken immediately prior to a platelet
(Caridian BCT, Inc, Lakewood, CO, USA). Hb was
donation.
determined by using a Coulter LH 500 haematology
Individuals entering the study were given an infor-
analyser (Beckman Coulter, Inc, Fullerton, CA, USA)
mation sheet explaining the aims of the study and the
using diluent and reagents from Beckman Coulter.
process they would undergo, and written consent was
Reference values were supplied by Beckman Coulter.
obtained. Subjects who were found to have a serum
The reference range for males was Hb 130–170 g L−1
ferritin level below the normal reference range were
and for females was Hb 120–160 g L−1 .
advised to consult their General Practitioner (GP) who
Ferritin was determined by using a Hitachi Modular E
was given details of the results. Such individuals were
floor model analyser and reagents from Roche Diagnos-
advised to refrain from donation for a period of up to
tics (Mannheim, Germany). Reference values for ferritin
6 months, whilst investigation and treatment was deter-
were established to 95% confidence (two standard devi-
mined by their GP.
ations). The reference ranges for ferritin were males
All those participating in the study were required to
30–400 ng/mL, females age 14 years up to 50 years
complete a questionnaire giving information on diet,
13–200 ng/mL and females older than 50 years of age
iron supplementation and whether they had any con-
30–400 ng/mL.
dition possibly causing blood loss such as haemor-
rhoids or symptoms of gastritis. Additionally, females
were asked to confirm whether they were pre- or
RESULTS
post-menopausal and whether they had heavy periods.
Those who responded positively were excluded from the The results in Table 1 show that 40% (70/175) of
study. males donating regularly by plateletpheresis for less than
All participants in the study, both donors and non- 3 years and 32·6% (61/187) of males donating regularly
donors, were selected according to the standard criteria by plateletpheresis for more than 3 years had low iron
for whole blood and component donors as outlined stores as indicated by having serum ferritin below the
in the Guidelines for the Blood Transfusion Services normal range of 30–400 ng/mL. It can clearly be seen
in the UK and the Donor Selection Guidelines (The in both cohorts that the number of donors with low
Stationary Office, 2005). A minimum haemoglobin level iron stores is related to the frequency of donation. The
of 135 g L−1 for males and 125 g L−1 for females is number of donors showing iron depletion is greater in
required for donation in the UK. Prior to acceptance the group donating for less than 3 years than in the group
on to the study, all participants were tested using a who have donated for more than 3 years. No donor who
gravimetric method with CuSO4 solution to determine donated at intervals of more than 8 weeks had deficient
that they satisfied these criteria. Donors who failed to iron stores.
achieve this standard using the CuSO4 solution test had In the cohort of male donors who had donated by
a further test on a venous sample using a haemoglobin plateletpheresis for less than 3 years, five donors had a
photometer (Hemocue) which was required to show the haemoglobin beneath the acceptance level for donation
desired haemoglobin level in order to allow them to which requires a male donor to have a haemoglobin of
proceed to donation. 135 g L−1 or above. All five subjects had a serum ferritin
concentration below the normal range. Four donors had
a haemoglobin between 130 and 135 g L−1 and one had
Samples
a haemoglobin of 115 g L−1 . This was a 48-year-old
One native 10 ml blood sample and one 5 ml sample man who had given 27 platelet donations at 6 weekly
in ethylenediaminetetraacetic acid (EDTA) were col- intervals and who had a serum ferritin of 25 ng mL−1 .
lected into plastic tubes immediately prior to dona- In the cohort of male donors who had donated by
tion. The native sample was transported to the Whit- plateletpheresis for more than 3 years, three donors had
tington Hospital laboratory for serum ferritin analysis haemoglobin levels between 132 and 134 g L−1 .
where samples were stored unseparated at 4 ◦ C. Sam- Table 2 shows the results for female donors. As
ples were then centrifuged at room temperature prior to expected, the percentage of post-menopausal female
assay. donors with serum ferritin below range is similar
The EDTA samples were stored at room temperature to those found in the male donors. Notably, only
overnight before being analysed for full blood count at 11·1% (5/45) of pre-menopausal female plateletphere-
NBS testing laboratories. sis donors had a serum ferritin below the normal range
© 2009 The Authors
Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29
24 E. A. Page et al.

Table 1. Number and percentage of male platelet donors with serum ferritin below normal reference range of 30 ng/mL∗

Donation Male plt donors Number with serum Male plt donors Number with serum
frequency donated <3 years ferritin <30 ng/mL donated >3 years ferritin <30 ng/mL

Total donors (all 175 70 (40%) 187 61 (32·6%)


frequencies)
2 weekly 34 21 (61·8%) 38 25 (65·8%)
3 weekly 38 18 (47·4%) 49 18 (36·7%)
4 weekly 69 23 (33·3%) 64 14 (21·9%)
5–6 weekly 20 6 (30%) 23 4 (17·4%)
8 weekly 8 2 (25%) 7 0
9–16 weekly 6 0 6 0

Plt, platelet.
∗ Serum ferritin range for males = 30 − 400 ng/mL.

for pre-menopausal women (13–200 ng/mL). There is donors all had normal iron stores as indicated by ferritin
no correlation with frequency of donation though this levels within the normal range.
may reflect the small number of iron depleted subjects Donors were questioned as to whether they were
studied. currently taking iron supplementation. Of the 362 male
Of the non-donors sampled, 3·2% (3/101) – one male plateletpheresis donors, 15 (4·1%) admitted to taking
and two pre-menopausal females – were found to have iron. Of the 15 donors taking iron supplementation,
a serum ferritin below the normal range. two (13·3%) had a serum ferritin level below the
Results were considered in terms of the lifetime num- normal range. One donated at 2 weekly intervals, the
ber of plateletpheresis donations made. Table 3 shows other at 3 weekly intervals and both donors had a
little correlation between the number of plateletpheresis normal haemoglobin level of 141 g L−1 and 159 g L−1 ,
respectively. Four female donors, all post-menopausal,
procedures and donor iron stores in the male donors.
admitted to taking iron supplementation. Two (50%) of
In order to ascertain the influence of previous whole
these had serum ferritin levels below the normal range
blood and plasmapheresis as well as platelet donations
and both donated at 3 weekly intervals. No non-donor
in the donor’s lifetime, data were analysed according
reported taking iron supplementation.
to the donor’s credited numbers of donations on the
NBS computer system. Prior to 1992, donation type is
not itemized so there is no way of identifying whether DISCUSSION
the donations given were of whole blood, plasma or
platelets. The total number of donations (whether whole It has been appreciated that regular blood donors will
blood, plasma or platelets) credited by the computer has become iron depleted, particularly if they donate at
been listed in Table 4. the maximum frequency allowed under NBS, England
The minimum number of donations before any subject and Wales (NBS) policy. The development of ferritin
showed depleted iron stores was 14, the donor having assays (Cook et al ., 1976) in the 1970s led to a
greater understanding of the effects of regular donation
given 11 blood donations prior to three plateletpheresis
with studies showing that regular blood donation is
donations. Otherwise, as shown in Table 4, there is little
accompanied by progressive decline of serum ferritin
correlation between deficient iron stores and the lifetime
concentration (Finch et al ., 1977; Simon et al ., 1981;
number of donations either in males or females.
Milman et al ., 1998). A blood donor donating at the
Of the 460 donors on the study, 11 (2·4%) were maximum frequency allowed under NBS policy of
vegetarian, whilst all other donors ate red meat at least three or four times in a year will lose 1500–2000 mL
once a week. Of the 10 males who were vegetarian, of blood per annum. A study (Taylor & Harrison,
40% (4/10) were iron deficient though not anaemic, a 2000) by the NBS showed 83% of a sample of 41
similar percentage to the whole study population. Two regular male blood donors who had donated a lifetime
of the iron depleted vegetarian donors donate at 2 weekly average of 74 units including eight times within the past
intervals and two at 4 weekly intervals. The one female 2 years had a serum ferritin below the normal range.
donor who was a vegetarian was iron depleted. Three In contrast, 22% of 18 male donors with a lifetime
of the 101 (2·97%) non-donors were vegetarian and average of 14 donations, up to three donations in the
a further two ate no red meat whatsoever. These five past 2 years and no donation in the past 6 months had
© 2009 The Authors
Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29
Iron stores in plateletpheresis donors 25

the past 6 months had a serum ferritin below the normal

<30 ng/mL
Se ferritin

9 (42·9%)
4 (30·1%)
20 (37·7%)
2 (40%)
5 (50%)
range.

0
0
The daily iron requirement for an adult male is
1·0 mg and for an adult menstruating female 1·5–2 mg
menopausal (Harrison, 2008). A blood donation of 470 mL plus
30 mL samples (500 mL blood loss in total) contains
Post-

approximately 250 mg of iron, so that a donor will need


53

10
21
13
5

2
2
to absorb 0·7 mg of iron daily (250/365) for each unit
donated per year. A person eating a western diet can
expect to absorb between 1 and 4 mg of iron per day.
<13 n g/mL
Se ferritin

5 (11·1%)

1 (11·1%)
Thus, anyone who donates blood three to four times
2 (40%)

2 (10%)
0

0
0 per annum may have difficulty maintaining adequate or
normal iron stores.
At the time of this study in England and Wales,
menopausal

plateletpheresis donors were invited to donate at a


minimum interval of 2 weeks but no more than 24
Pre-

45
5
4
20
9
4
3

times a year. Blood loss within the harness (Gam-


bro BCT, 2004) and at sampling on the Trima Accel
cell separator is between 80 and 100 mL resulting in
(post-men) <13 ng/mL
Se ferritin <30 ng/mL

an annual blood loss of up to 2400 mL in some-


Table 2. Number and percentage of female platelet donors with serum ferritin below normal reference range∗

∗ Serum ferritin range for pre-menopausal females = 13 − 200 ng/mL and for post-menopausal females = 30 − 400 ng/mL.

one donating at the maximum frequency. This is the


7 (30·4%)
3 (23·1%)
(pre-men)

equivalent of four to five whole blood donations per


3 (50%)
3 (50%)
16 (32%)

annum. Studies in repeat apheresis donors have shown


0
0

serum ferritin levels decreasing in a donation-frequency


dependent manner, with females showing significantly
decreased ferritin levels with over 21 donations (Furuta
et al ., 1999).
Whilst some authors have questioned the relevance
>3 years
Donated

of iron depletion short of anaemia (Verloop, 1970),


50
6
6
23
13
1
1

others have demonstrated adverse clinical effects in


some situations. There is evidence of reduced intellec-
tual capacity in non-anaemic iron deficient children and
(post-men) <13 ng/mL
Se ferritin <30 ng/mL

adolescents (Gordon, 2003). A joint study from South


Plt, platelet; post-men, post-menopausal; pre-men, pre-menopausal; Se, serum.

Africa and the United States in 2003 (Beard et al ., 2003)


9 (18·8%)

4 (22·2%)
2 (22·2%)
(pre-men)

showed a significant correlation between iron status and


1 (25%)
2 (25%)

impaired cognitive functioning, depression, anxiety and


0
0

anger, in women with iron-deficiency anaemia, and in


iron depleted but non-anaemic women. Furthermore, a
recent case report (Page et al ., 2008) described a regular
plateletpheresis donor who donated at 2 weekly intervals
and who developed an impairment of anterograde mem-
<3 years
Donated

ory coupled with moderate depression in the presence


48

18
4
8

9
5
4

of a non-anaemic iron depletion. Following iron therapy


and a return of his iron stores to normal levels, there was
a marked improvement in his memory testing scores and
Total donors (all frequencies)

a recovery from his depression.


The results from the study reported here show that
33·9% (156/460) of plateletpheresis donors had serum
ferritin concentrations below the normal range, with
those who had donated for less than 3 years showing
12–16 weekly
8–10 weekly
5–6 weekly

similar or even greater levels of iron depletion to those


frequency
Donation

2 weekly
3 weekly
4 weekly

who had been donating for more than 3 years. About


23·8% (5/21) of donors who had given only one to
four platelet donations were iron depleted. However, it
© 2009 The Authors
Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29
26 E. A. Page et al.

Table 3. Number and percentage of platelet donors with serum ferritin below normal reference range according to lifetime number of platelet donations∗

No. platelet Se ferritin <30 ng/mL Se ferritin Pre-men Se ferritin Post-men Se ferritin
donations All donors male Males <30 ng/mL females <13 ng/mL females <30 ng/mL

Total donors 460 156 (33·9%) 362 131 (36·2%) 46 6 (13%) 52 19 (35·5%)
1–4 21 5 (23·8%) 17 5 (29·4%) 3 0 1 0
5–9 31 8 (25·8%) 18 5 (27·8%) 9 1 (11%) 4 2 (50%)
10–14 56 15 (26·8%) 43 14 (32·6%) 5 0 8 1 (12·5%)
15–19 52 15 (28·8%) 38 12 (31·6%) 9 0 5 3 (60%)
20–24 38 17 (44·7%) 30 14 (46·7%) 3 1 (33·3%) 5 2 (40%)
25–29 27 9 (33·3%) 24 8 (33·3%) 1 0 2 1 (50%)
30–39 42 17 (40·5%) 38 17 (44·7%) 2 0 2 0
40–49 32 9 (28·1%) 23 7 (30·4%) 2 0 7 2 (28·6%)
50–74 51 15 (29·4%) 41 10 (24·4%) 4 2 (50%) 6 3 (50%)
75–99 42 23 (54·8%) 33 20 (60·6%) 6 2 (33·3%) 3 1 (33·3%)
100–149 41 11 (26·8%) 33 8 (24·2%) 2 0 6 3 (50%)
150–199 19 8 (42·1%) 16 7 (43·8%) – – 3 1 (33·3%)
200–285 8 4 (50%) 8 4 (50%) – – – –

Plt, platelet; post-menopausal; pre-men, pre-menopausal; Se, serum; post-men.



Serum ferritin range for pre-menopausal females = 13 − 200 ng/mL and for males and post-menopausal females = 30 − 400 ng/mL.

Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29
© 2009 The Authors
© 2009 The Authors
Table 4. Number and percentage of platelet donors with serum ferritin below normal reference range according to lifetime number of total whole blood and pheresis
donations∗

No. platelet + whole Se ferritin<normal Se ferritin Pre-men Se ferritin Post-men Se ferritin


blood donations All donors range Males <30 ng/mL females <13 ng/mL females <30 ng/mL

Total donors 460 156 (33·9%) 362 131 (36·2%) 46 6 (13%) 52 19 (35·5%)
1–9 12 0 4 0 7 0 1 0
10–24 53 12 (22·6%) 39 10 (25·6%) 8 0 6 2 (33·3%)
25–49 103 36 (35%) 79 29 (36·7%) 10 1 (10%) 14 6 (42·9%)
50–74 95 28 (29·5%) 78 26 (33·3%) 7 0 10 2 (20%)
75–99 40 15 (37·5%) 31 12 (38·7%) 5 2 (40%) 4 1 (25%)
100–149 58 25 (43·1%) 50 21 (42%) 3 1 (33·3%) 5 3 (60%)
150–199 38 17 (44·7%) 33 15 (45·5%) 0 0 5 2 (40%)
200–249 12 6 (50%) 7 4 (57·1%) 5 2 (40%) 0 0
250–299 9 3 (29·4%) 9 3 (24·4%) 0 0 0 0
300–349 10 1 (10%) 7 0 0 0 3 1(33·3%)
350–399 3 2 (66·7%) 3 2 (66·7%) 0 0 0 0
400–499 13 4 (30·1%) 8 2 (25%) 1 0 4 2 (50%)

Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29
500–699 14 7 (50%) 14 7 (50%) – – – –

Plt, platelet; post-men, post-menopausal; pre-men, pre-menopausal; Se, serum.



Serum ferritin range for pre-menopausal females = 13 − 200 ng/mL and for males and post-menopausal females = 30 − 400 ng/mL.
Iron stores in plateletpheresis donors
27
28 E. A. Page et al.

was notable that no donor who had donated a total of side effects and donor compliance (Radtke et al ., 2004;
less than 14 blood and/or platelet donations was iron Boulton, 2008).
depleted suggesting the relevance of previous whole As a result of this study, we have advised that
blood donations. Thereafter, there was no correlation volunteers should not donate platelets more than 15
between lifetime number of donations and iron status. A times per year, so that red cell loss is no more than the
study evaluating the iron status of new plateletpheresis equivalent of three whole blood donations (1500 mL).
recruits may provide valuable information as to whether In 2008, the NBS changed its policy to reflect this
donors are already iron depleted at the point of entry on recommendation.
to the platelet programme and indicate whether sampling
of all new platelet recruits to determine their ferritin
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© 2009 The Authors


Journal compilation © 2009 British Blood Transfusion Society, Transfusion Medicine, 20, 22–29

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