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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 23-May-2008, Vol 121 No 1274

Iron status and risk-profiling for deficiency in New Zealand blood donors
Krishna G Badami, Kate Taylor
Abstract
Aim To assess the iron status of New Zealand blood donors using the serum ferritin (ferritin) assay and the impact of gender, age, and donation history on iron status.
Methods Ferritin levels were measured in 5006 subjects attending two New Zealand Blood Service (NZBS) blood donor sites between October and December 2006. The influence of three major determinants of iron status (gender, age, and blood donation history) in the previous 12 months was assessed.
Results Ferritin levels tended to be lower in younger people, females, and those with more intensive blood donation history. Levels lower than 12 mcg/L were found in 14.1% of subjects overall, 19.9% of females, 19.0 % of those aged under 20 years, and 25.1% of those who had donated 3–4 whole blood units during the previous 12 months had ferritin levels lower than 12 mcg/L. Risks were additive and total risk correlated inversely with ferritin levels.
Conclusions Iron deficiency is a significant problem in New Zealand blood donors. Prevention or treatment, as appropriate, would help both donors and the long-term supply of blood. A stratified approach to testing, prevention and treatment taking into account risk factors, ferritin and Hb levels is likely to be the most effective strategy.

Iron deficiency is a major health problem throughout the world including New Zealand. Indeed, some evidence shows that deficiency, even if insufficient to cause anaemia, may affect physical and mental performance and health. An individual’s iron status is a balance between intake, absorption, and loss.
Blood donation is a well-recognised risk factor for iron deficiency. Iron deficiency is probably the most significant impact of blood donation on donors. Current, ‘one size fits all’ protocols may be insufficient to prevent iron deficiency in some blood donors.
Published information on the iron status of New Zealand blood donors is limited.1 A study from the United States suggested that up to 8 and 23% of male and female donors respectively may be iron deficient.2
We report results from a two-site observational study on New Zealand blood donors which aimed to determine:
  • The iron status of current donors using the serum ferritin (hereafter termed ‘ferritin’) assay;
  • How iron status correlates with three important determinants—gender, age, and blood donation history; and
  • Groups at particular risk of becoming iron deficient.

Methods

The study was undertaken between October and December 2006 at the Christchurch and Waikato New Zealand Blood Service (NZBS) sites after approval by the multi-region ethics committee, Wellington.
Intending blood donors attending static and mobile venues were given an information leaflet and asked if they wished to participate. Inclusion in the study required:
  • Signed informed consent;
  • Satisfactory pre-donation health assessment (with the sole exception of a ‘low’ Hb—i.e. one that is less than acceptable for donation: <130 g/L and 120 g/L in males and females respectively);
  • Satisfactory post-donation blood test results (among others, antibody to and nucleic acid testing for HIV 1 and 2, HBsAg, antibody to and nucleic acid testing for HCV and the TPHA serological test for syphilis and, in first-time donors, antibody to HTLV I and II, in O negative donors and a proportion of other donors, antibody to CMV);
  • No adverse post-donation information.
Note: Blood donors routinely undergo health assessment which includes a questionnaire, an interview, pre-donation haemoglobin measurement and post-donation blood tests.
Ferritin was measured using a validated enzyme immunoassay (Abbot Axsym®). For the purposes of this study the iron status of subjects, based on the ferritin level was classified as:
  • ‘High’ (males >300 mcg/L; females >250 mcg/L);
  • ‘Normal’ (males >20–300 mcg/L; females >20–250 mcg/L),
  • ‘Borderline’ (males and females 12–20 mcg/L) or
  • ‘Low’ (males and females <12 mcg/L).
Subjects with normal results were not informed but were given the opportunity to discuss their results by telephone. Those with abnormal results were informed and advised to see their own doctors.
Demographic data and blood test results were taken from computer records and collated electronically. Data were analysed using the Epi Info 2000 statistics package.

Results

Of the 5046 participants approached, 5006 (99.2%) participants were recruited: 3001 from Waikato and 2005 from Christchurch. Figure 1 shows the study flow chart.
Characteristics of study subjects are shown in Table 1. They were comparable with those for New Zealand blood donors as a whole and subjects at the two sites were essentially comparable with each other.
Correlations between the three main variables (age, gender, and donation history) for the 5006 subjects are shown in Figures 2–4. Ferritin levels and the iron status of subjects are shown in Tables 2 and 3.
While the majority of subjects with a ‘low’ Hb (as previously defined) had a low ferritin, a substantial minority of those with acceptable Hb also had a low ferritin (Table 3); 99.0% of all subjects had an Hb that was acceptable for blood donation (Table 3) as did 1694/1730 (97.9%) of subjects with a low or borderline iron status.
Gender, age, and prior donation history influence the risk of becoming iron deficient (Tables 2 and 3). Risk categorisation by cumulative risk scores based on these variables is shown in Table 4 and the correlation between risk category and ferritin level is shown in Table 5. Though this model has not been validated and is incomplete (not having taken in to account other determinants of iron status), it has biological basis3 and our results suggest that there is a good correlation.
In the scheme described above, cumulative risk scores 5 and 4 (together 6.1% of all subjects) might represent ‘high risk’, 3 and 2 (55.0%) ‘intermediate risk’, and 1 and 0 (38.7%) ‘low risk’ for iron deficiency.

Figure 1. Study flow chart

Note: Includes 48 ineligible to donate on account of ‘low’ Hb but eligible for the study; DA testing=donor accreditation testing (post-donation blood tests), Hb=haemoglobin.

Table 1. Characteristics of subjects in the study compared to New Zealand blood donors in 2006. All values are shown as n (%)

Variables
Study subjects
All NZBS donors 2006
5006
94288
Donation
Venue
static
mobile
2817 (56.2)
2189 (43.7)

Gender
males
females
2395 (47.8)
2611 (52.1)
44267 (46.9)
50021 (53.0)
Age group
<20
21–50
>51
415 (8.2)
2867 (57.2)
1724 (34.4)
14955 (15.8)
52129 (55.2)
27204 (28.8)
Blood donation
history in previous 12 months
3–4 whole blood (WB)
1–2 WB / >15 pheresis (ph)
927 (18.5)
2758 (55.0)
28053 (29.7)
27357 (29.0)
1–14 ph
Nil
300 (5.9)
1021 (20.3)
3168 (3.3)
35710 (37.8)
Blood group
O negative
other
583 (11.6)
4423 (88.3)
9849 (10.4)
84439 (89.5)

Table 2. Serum ferritin levels (mcg/L) and subject characteristics

Variables
Mean (SD)
Median
P value
Location
(n, %)
Waikato (3001, 59.9)
Christchurch (2005, 40.0)
51.2 (52.7)
41.7 (30.7)
35.6
29.8
<0.001
Gender
(n, %)
males (2395, 47.8)
females (2611, 52.1)
64 (58.4)
32.2 (30.7)
47
24.6
<0.001
Age
(n, %)
<20 (415, 8.2)
21-50 (2867, 57.2)
>51 (1724, 34.4)
33.5 (29.8)
47.3 (49.3)
51.0 (50.9)
26.6
31.9
36.7
<0.001
Donation history
(n, %)
3–4 WB (927, 18.5)
1–2 WB/>15 ph (2758, 55.0)
<14 ph/nil (1321, 26.3)
29.1 (27.6)
45.3 (45.9)
70.2 (64.9)
22.1
33.2
49.9
<0.001
Blood group
(n, %)
O negative (583, 11.6)
other (4423, 88.3)
41.3 (45.1)
48.3 (49.1)
27.5
33.7
<0.0001
Hb (n, %)
‘low’ (49, 0.9)
adequate (4957, 99.0)
17.8 (24.2)
47.7 (48.6)
7.7
33.2
<0.0001
Overall (n=5006)
47.5 (48.7)
33.0


Table 3. Iron status and subject characteristics

Variables
Iron status (% in each category)
high
normal
borderline
low
p value
Location (n, %)
Waikato (3001, 59.9)
Christchurch (2005, 40.0)
0.6
0.3
68.7
59.1
17.5
24.6
13.0
15.8
<0.001
Gender (n, %)
males (2395, 47.8)
females (2611, 52.1)
0.8
0.2
71.0
59.2
20.2
20.5
7.8
19.9
<0.001
Age (n, %)
<20 (415, 8.2)
21–50 (2867, 57.2)
>51 (1724, 34.4)
0.2
0.5
0.6
54.4
63.3
69.9
26.2
20.4
18.9
19.0
15.6
10.4
<0.001
Donation history (n, %)
3–4 WB (927, 18.5)
1–2 WB / >15 ph (2758, 55.0)
<14 ph/nil (1321, 26.3)
0
0.4
1.3
40.2
65.2
81.0
34.6
20.1
11.2
25.1
14.1
6.2
<0.001
Blood group (n, %)
O negative (583, 11.6)
other (4423, 88.3)
0.3
0.6
57.8
65.8
25.0
19.8
16.8
13.8
0.001
Hb (n, %)
‘low’ (49, 0.9)
0
0.5
24.4
65.2
12.2
20.4
61.2
13.6

adequate (4957, 99.0)
Overall (n=5006)
0.5
64.9
20.4
14.1


Figure 2. Proportions (%) of males and females in the 3 age groups

Figure 3. Gender and prior donation history

Figure 4. Age and prior donation history

Table 4. Cumulative risk (risk categories) based on gender, age, and prior donation history

Variables
Prior donation history
Gender
Age
3–4 WB
(2 points)
1–2 WB / >15 ph
(1 point)
<14 ph/nil (0 points)
Female
(1 point)
<20 y
(2 points)
5
4
3
21–50 y
(1 point)
4
3
2
>51 y
(0 points)
3
2
1
Male
(0 points)
<20 y
(1 point)
3
2
1
>21 y
(0 points)
2
1
0

Table 5. Ferritin levels (mcg/L) according to cumulative risk (risk category) for iron deficiency)—all subjects combined

Variables
Cumulative risk (risk category)
5
4
3
2
1
0
Number (%) in each risk category
19 (0.37)
292 (5.8)
1132 (22.0)
1605 (32.06)
1463 (29.22)
478
(9.54)
Mean ferritin
11.4*
18.1
26.1*
37.7
63.8
101.0
SD
7.2
14.4
25.9
31.6
53.6
73.2
Median ferritin
8.0
14.3
20.4
29.0
49.7
76.4
*P value <0.0001 comparing the mean ferritin for categories 3 and 5.

Discussion

This is the first systematic assessment of iron status in a broad range of New Zealand blood donors. Our results show that iron deficiency is a significant problem in this group (Tables 2 and 3). Overall 14.1% and 20.4% of subjects had low or borderline iron status respectively. Current standards (see later), protect donors poorly in this regard. The vast majority (97.9%) of subjects with a low or borderline iron status had an Hb that was adequate for donation
The proportion of iron-deficient subjects in this study is similar to those in previous reports on blood donors1,2,4–6 but higher than those in New Zealand population-based reports (with some exceptions).7–10 Direct comparisons are difficult because of inconsistencies in the use of terms such as ‘donor’ and ‘non-donor’ and in the ferritin levels defining iron deficiency.
As expected, females, subjects aged under 20 years (y) and those with more intense prior donation history had lower ferritin levels and significantly worse iron status (Tables 2, 3). While the relationship between gender and prior donation history is not clear-cut (Figure 3), it is unlikely that prior donation history alone is sufficient to explain the worse iron status of female subjects.
Factors not evaluated in the present study such as diet and menstruation are likely to be more important. The relatively poor iron status of <20 y subjects is possibly due to the combined effect of increased iron requirements during growth and inadequate intake. Indeed, several studies have confirmed the relatively poor iron intakes and iron status in adolescents—especially, girls.11–13
Intensity of blood donation during the previous 12 months was inversely and significantly related to ferritin (Tables 2, 3).Those with the highest two levels of prior donations, constituting 73.5% of all subjects (Table 1) accounted for 687/751 (91.4%) of those with low ferritin.
Red RBC (and hence iron) loss depends on the number and type of donation. NZBS standards permit up to 4 whole blood donations or (at that time) up to 15 L of plasma in a 12-month period with at least 90 days between successive whole blood and 14 days between successive phereses donations subject to satisfactory pre-donation health assessment as described under methods.
Loss of packed RBC is 175–330 ml with a whole blood donation and, in our set-up, 10–15 ml with a pheresis donation. Additional losses of blood occur—for routine blood tests in all donors and, for instance, the initial blood draw into the diversion pouch (to reduce bacterial contamination) in plateletpheresis donors.
The relationship between ABO/RhD group, ferritin levels, and donation frequency has not previously been commented on. In this study, O negative subjects had significantly lower ferritin levels (Tables 2 and 3) perhaps because they donate blood more intensively than those of other groups. 54.2% and 26.5% of O-negative subjects donated 3–4 WB units and 1–2 WB / >15 ph units respectively during the previous 12 months compared to 48.5% and 15.4% respectively for those of other groups.
Waikato subjects had significantly higher ferritin levels than Christchurch subjects, lower proportions of those with low and borderline ferritin, and higher proportions of those with normal and high ferritin (Tables 2 and 3). The reasons are not clear. Christchurch had slightly more O negative donors and subjects donating more intensively in the previous 12 months compared to Waikato. Waikato though, had a slightly higher proportion of females and <20 y subjects than Christchurch (results not shown) and possibly also a higher proportion of Māori subjects.
In the last National Nutrition Survey (NNS 97),7 Māori (especially women) appeared to have a worse iron status than that of their ‘European and Other’ counterparts. Factors not considered in the current study (such as ethnicity, dietary iron intake and absorption, body-mass index, menstruation, oral contraceptive vs intrauterine device use, and causes of ‘falsely’ elevated ferritin) may explain the difference between the two sites.
Individuals with latent iron deficiency (low ferritin but ‘normal’ Hb and red cell indices) may show increase in both Hb and indices as iron status improves. Furthermore, latent iron deficiency may be associated with a variety of significant, though sometimes subtle, health problems such as fatigue,14 low physical endurance,15,16 impaired cognition,17,18 and the restless leg syndrome.19
A small minority of subjects with borderline or normal ferritin (6/1022 and 12/3249 respectively) but none with raised ferritin also had ‘low’ Hb but they were not further investigated by us. Explanations include:
  • Hb that was normal for the individual concerned but less than acceptable for donation;
  • Technical causes affecting either the Hb or ferritin assays;
  • Iron deficiency anaemia masquerading as normo-ferremic anaemia because of associated anaemia of chronic disease, acute phase reaction or other causes; and
  • Anaemia due to causes other than iron deficiency.
While the majority of subjects with a ‘low’ Hb had a low ferritin, a substantial minority of those with acceptable Hb also had a low ferritin (Table 3) thus confirming again that anaemia develops late in iron deficiency. It is sobering to note that 13.6% and 20.4% of the 4957 subjects who actually donated blood had low or borderline iron status respectively on the day they donated blood (Table 3).
Only 1% of all subjects (and 4.3% of those with a low ferritin) had a ‘low’ Hb. Normally we would detect a higher proportion of intending blood donors with a low Hb. The low numbers of ‘Hb failures’ in this study may have resulted from the low enrollment of subjects with low Hb. Nevertheless, our results suggest that the magnitude of the problem of iron deficiency amongst New Zealand blood donors is perhaps no less than stated.
In this connection it is interesting to consider ferritins routinely checked in 1077 intending blood donors with a low Hb at the Christchurch centre between July 2001 and February 2007 (not part of the current study). This ranged from 1–464 mcg/L, the mean was14.9 mcg/L and the median 6.0 mcg/L. Of these, 2 (0.18%), 148 (13.7%), 138 (13.7%), and 789 (78.3%), would have been classified as iron status high, normal, borderline and low respectively according to the criteria used in this study.
Risks for iron deficiency are additive and a combination of factors determines overall risk (Table 5). In this study, gender, age, and prior donation history were evaluated. As expected, male donors, in general, are able to maintain iron levels better than females. For example, the mean serum ferritin in males aged >21 y donating 3–4 WB units during the previous 12 months was comparable (results not shown), not to that of females >51 y with a similar donation history, but to >51 y female subjects with a past history of 1–2 WB or pheresis equivalents.
Interestingly 27/5006 (0.5%) subjects had higher than normal ferritin including 13/2758 (0.4%) of those who had donated 1–2 whole blood units or >15 phereses units, 6/2611 (0.2%) of females and 1/415 (0.2%) of those <20 y [Table 3].
In blood donors, raised or high-normal ferritin for reasons other than genetic haemochromatosis (HC) are possible but unlikely. Indeed, some subjects may have been patients with known HC (but accepted as blood donors) and some who were previously undiagnosed have since had HC formally confirmed. While the serum ferritin assay is not a good test for early HC, in blood donors it is likely to uncover at least some cases of HC—an example of ‘value addition’ to the donation process (from the perspective of the donor) that has recently been mooted.20

Conclusions and Recommendations

A significant proportion of New Zealand blood donors have poor iron status. As expected, female gender, lower age, and more intensive blood donation history predict poor iron status. Current protocols protect blood donors poorly from iron deficiency.
Iron deficiency affects donor health, donor retention, and blood supply. The latter possibility been discussed in a previous publication.21 Amongst New Zealand blood donors, Hb failure is the prime single reason for deferral accounting for 20% of all deferrals in 2006–2007 (internal NZBS data). Most of these are likely to be due to iron deficiency.
This study has not considered all the risk factors for iron deficiency and a further study is planned to consider factors such as diet, menstruation, ethnicity, and BMI. However, even on the basis of the information currently available, individually tailored protocols can be created that are better able to preserve donor iron status.
Changes to donation protocols, if stratified by risk should not prove too difficult to implement because only a minority of subjects (6.1%) in our study were in a putative ‘high risk’ group requiring particular attention while 55.0% and 38.7% respectively were in ‘intermediate’ and ‘low’ risk categories (Table 5).
Reducing donation frequency alone, in order to improve donor iron status, may lead to unacceptable reduction in supply—at least in the short-term. A stratified protocol taking into account risk, (but also Hb and ferritin) and incorporating testing for deficiency, prophylaxis or, treatment with iron supplements as appropriate and follow-up is the one most likely to reconcile the conflicting demands of blood supply and donor well-being.
Competing interests: None known.
Author information: Krishna G Badami, Transfusion Medicine Specialist, New Zealand Blood Service, Christchurch; Kate Taylor, Medical Officer, New Zealand Blood Service, Hamilton
Acknowledgements: We are grateful to the following people and organisations for their assistance:
  • Donor room and reception staff at NZBS Christchurch and Waikato
  • Donor accreditation laboratory staff at NZBS Christchurch and Auckland
  • Carolyn Jeffrey and colleagues, IT Dept, NZBS National Office
  • NZBS Clinical Advisory Group
  • Dr Sue Levin (Medical Officer, NZBS Christchurch)
  • Dr Anita Bell (Public Health Physician, Waikato District Health Board)
  • Maree Clarkin (Collections Support Officer, NZBS Waikato)
  • Olive Utiera (National Manager, Donor Services, NZBS)
  • Rosie Hawes (Manufacturing Support Officer, NZBS Christchurch)
  • Glenys Whitelaw (Executive Assistant, Donor Administration, NZBS Christchurch)
Correspondence: Dr Krishna G Badami, Transfusion Medicine Specialist, New Zealand Blood Service, 87 Riccarton Rd., Christchurch, New Zealand. Email: krishna.badami@nzblood.co.nz
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