The importance of iron for whole blood donors: a Canadian perspective
- Iron deficiency is common in whole blood donors, particularly female donors, frequent donors, and donors failing their hemoglobin (Hb) screening test.
- In 2017, Canadian Blood Services increased the donation interval for female whole blood donors to 84 days (from 56 days) to reduce the risk of iron deficiency in these donors.
- Whole blood donors should speak to their physician about iron supplementation to replenish lost iron stores from blood donation. A diet rich in iron is recommended for all blood donors but this may not be sufficient to restore normal ferritin levels.
- Physicians should order serum ferritin levels on patients that are frequent whole blood donors (more than three whole blood donations per year for males and more than one whole blood donation per year for females).
- Physicians should consider iron supplementation in all patients that are blood donors. A daily supplement (37.5 mg of elemental iron) for 8 weeks should be sufficient to replenish iron losses from a whole blood donation.
By generously providing blood that can be manufactured into red blood cells, platelets and plasma products, whole blood donors are essential to the blood system and the patients it serves. Canadian Blood Services is committed to maintaining a safe and secure blood supply while also protecting the health of our blood donors. The focus of this article is the effect of red blood cell loss on the iron levels of the donor and the steps taken by Canadian Blood Services to protect the health of its donors.
Red blood cells are the most abundant cell type in blood. They are packed with hemoglobin molecules that are responsible for the transport of oxygen from lungs to the organs and tissues throughout the body. Iron is a vital building block of hemoglobin; each hemoglobin molecule is composed of four iron atoms. Iron is an essential element obtained through the diet and used for biochemical functions throughout the body. This can be illustrated with a passenger car and ferry analogy: the iron provides the seat for oxygen in the hemoglobin vehicle, which is transported in the red blood cell ferry. The ferry delivers its cargo to organs and tissues, after travelling through arteries, veins and capillaries.
Iron stores in the body
Iron is stored in liver cells as well as within a protein shell called ferritin. Serum ferritin reflects the level of iron stores in the body and can be measured by analyzers in the laboratory. Whole blood donors are required to pass a fingerprick hemoglobin screening test using a portable hemoglobinometer; however, ferritin testing is not available at blood donor clinics.
Cooper et al. (2012) report that the prevalence of sufficient serum ferritin (defined as above the reference range) for Canadians in the 20 to 49 year old age group is 98.7% for males (95% confidence interval, CI, 97.5–99.9) and 90.9% for females (95% CI 87.2–94.6).1 Females had a statistically significant (p<0.05) lower ferritin level than males and the highest prevalence of insufficient serum ferritin was among females aged 12 to 19 (13%).1 With a single whole blood donation of 500 ml, there is an expected loss of 225–250 mg of iron. This loss may lead to serious health problems if not replenished through an iron-rich diet and/or iron supplementation. It is estimated that 25% to 35% of whole blood donors become iron-depleted (defined as ferritin below 26 µg/l) from regular whole blood donation.2 An iron supplementation (37.5 mg of elemental iron) consumed daily for eight weeks is expected to replenish the iron loss from one whole blood donation.2
Symptoms of iron deficiency and iron deficiency anemia
Iron deficiency can occur with or without anemia (i.e. low hemoglobin). The current donor hemoglobin screening process at Canadian Blood Services will detect and defer donors who have iron deficiency that results in anemia but not those who have non-anemic iron deficiency (NAID).
Symptoms of NAID have mainly been studied in premenopausal women. One-fourth of menstruating women have iron deficiency (defined as ferritin below 15 µg/l); fatigue is the most commonly reported symptom.3-6 According to Kiss et al. (2015), iron depletion is associated with fatigue, decreased exercise capacity, neurocognitive changes, pica and restless leg syndrome.2 Many studies examining NAID describe an association of symptoms rather than a definitive correlation.7 There is evidence that NAID impairs quality of life.3, 8, 9
The physiological manifestations of iron deficiency anemia include reduced immune function, impaired cognitive performance, behavior changes, decreased thermoregulatory performance and energy metabolism, and diminished exercise or work capacity.10,11 The broad range of symptoms related to iron deficiency is attributed to the many physiological uses of iron.
If iron deficiency is not treated, it may progress to iron deficiency anemia. It is important for blood donors and their physicians to be aware of the link between whole blood donation and iron deficiency to avoid unnecessary diagnostic tests for otherwise-healthy individuals developing iron deficiency after blood donation.12-14
|Iron status||Serum ferritin levels|
|Absent iron stores||< 12 µg/l|
|Low iron stores||12–24 µg/l|
|Adequate iron stores||> 25 µg/l|
Iron status of Canadian Blood Services’ whole blood donors
Canada’s fresh blood products are provided by approximately 415,000 volunteer donors. Each year, Canadian Blood Services collects approximately 790,000 units of whole blood. A dedicated group of repeat donors provides close to 87% of donations, while 13% of donations come from first time donors. The average whole blood donation frequency in 2018 was slightly over two donations per donor yearly.
Donor hemoglobin screening is performed on a fingerstick capillary sample prior to each whole blood donation, with a minimum qualifying level of 125 g/l required for female donors and 130 g/l for male donors. In 2018, 8% of female donors and 2% of male donors were temporarily deferred from donation for a low hemoglobin level. A low hemoglobin level can be a late consequence of iron depletion but may also, less commonly, be due to other etiologies (e.g. vitamin B12 deficiency, bone marrow pathology).
Canadian Blood Services does not routinely measure donor iron stores. There is increasing evidence that whole blood donation may cause iron deficiency, particularly in female and frequent male donors.13-17 At Canadian Blood Services, the hemoglobin-related donor deferral rate increases with frequency of whole blood donation. The correlation between blood donor status and iron deficiency may be under-recognized both by donors and their physicians.12-14 Iron status is recognized as a donor safety issue based on the associated symptoms of iron depletion discussed above.
Canadian Blood Services recently performed studies to assess the prevalence of iron deficiency in its whole blood donors by measuring ferritin levels in approximately 13,000 donors (i.e. 2.6% of our donor base).16,18,19 Donor clinics across Canada were randomly selected to have donor ferritin levels tested. Donors with low ferritin received an information sheet and a letter advising them to see their physician or pharmacist about starting iron supplementation. In addition, we evaluated donors’ knowledge of the impact of blood donation on their iron levels, and assessed the discussions that they may have had with their family physician about iron and blood donation.
The main findings of the studies were:
- Donor knowledge about iron is poor, and few donors discuss blood donation with their physician.
- Repeat donors are often iron deficient despite passing a hemoglobin screen (Table 1).
- Most donors failing their hemoglobin screen are iron deficient (Table 1).
- Donors with low ferritin are not always advised to take iron supplements by their physician.
- Many donors will start iron supplementation if advised to do so by their physician.
Adapted from Goldman et al. (2017).18
These results in Canadian donors are similar to those seen in studies performed in the US, Australia, Switzerland, the Netherlands, and Denmark.20-27 As in other countries, donor sex and frequency of donation were the main determinants of iron deficiency in whole blood donors.15, 25-27
Notifying donors about their iron deficiency was effective and resulted in a lower donation frequency in the two-year follow-up period, compared to donors with normal ferritin levels (who were not notified). Qualitative interviews with donors revealed that general comprehension about the relationship between hemoglobin and iron was poor, donors were not well informed to deal with the side effects of iron therapy, and their discussions with physicians were often limited and occurred at their annual check-up.
These internal studies combined with results from international studies were the basis for implementing iron deficiency mitigation steps at Canadian Blood Services. Additional studies are required to successfully implement a ferritin testing strategy for whole blood donors and to develop the optimal intervention in donors found to be iron deficient.
Iron deficiency mitigation steps at Canadian Blood Services
Recommendation 1. Donors failing their hemoglobin screen should follow up with their physicians to have their ferritin levels tested and to discuss iron supplementation.
Our studies demonstrated that the majority of whole blood donors who fail their hemoglobin screen have low iron stores (ferritin 12–24 µg/l) or absent iron stores (ferritin < 12 µg/l). Investigations may include a repeat of the hemoglobin measurement on a venous sample, as part of a complete blood count done on a laboratory analyzer. This test is more accurate than the fingerstick hemoglobin performed on a portable hemoglobinometer in donor clinics. Follow-up testing may include a serum ferritin level. Other investigations may be appropriate, depending on a variety of factors. These include the presence of iron deficiency alone or iron deficiency anemia, the patient’s age and sex, menstrual status, family history of gastrointestinal cancer, and the presence of any symptoms or signs of possible underlying conditions. Guidelines developed by the British Society of Gastroenterology recommend obtaining a history of blood donation as part of the investigation of iron deficiency.28 A trial of iron supplementation, temporary cessation of blood donation, and another evaluation of hemoglobin and ferritin after six months may be appropriate in a young female repeat blood donor, while a gastrointestinal investigation may be indicated in a first-time older male donor.
Those with a personal or family history of hemochromatosis should not be on iron supplementation. On the information sheet (Figure 1), donors are advised not to return to donate until they have seen their physician and determined the cause of the anemia. If donors are placed on iron supplementation for iron deficiency anemia, they are advised not to return to donate until they have completed six months of iron supplementation and the iron deficiency anemia has resolved.
Recommendation 2. Donors who pass their hemoglobin screen should have their ferritin levels tested if they are frequent donors or show symptoms of iron deficiency.
Since iron deficiency is so common in regular whole blood donors, we recommend that donors and physicians discuss blood donations during regular check-up visits. Individuals with possible symptoms of iron deficiency, such as unexplained fatigue, should have serum ferritin levels measured. Additionally, individuals who are donating frequently, particularly females donating at least twice a year and males donating three or more times a year, have a high likelihood of iron deficiency and should have serum ferritin levels measured.
Studies have shown that supplementation of 2000 to 4000 mg of elemental iron as a total dose will replace the iron lost in one whole blood donation.12,29 An iron supplementation dose of 37.5 mg of elemental iron taken daily for eight weeks should replenish the iron loss with a whole blood donation.2 For individuals donating on a regular basis, particularly females, it is very difficult to replace the amount of iron lost in donation by diet alone or by multivitamins that contain a small amount of iron.3 Table 2 shows some iron preparations available in Canada, and the number of tablets necessary to replace the iron lost in each whole blood donation. In most studies of iron supplementation in blood donors, donors have been advised to take one tablet daily at bedtime, preferably on an empty stomach, for a one to three month period to replace iron loss. Individuals with low ferritin levels will require a longer period of iron supplementation to replenish their iron reserves.
As shown in our study and by Statistics Canada, many female donors already have low iron reserves before starting to donate blood. Donors taking iron supplementation (37.5 mg of elemental iron daily) return to their pre-donation hemoglobin levels faster (4–5 weeks) versus those who did not take an iron supplement (11–23 weeks).2 Oral iron supplementation for eight weeks has been shown to improve total body iron after a whole blood donation.30 Individuals taking iron supplements who have been diagnosed with iron deficiency without anemia are advised to resume donation after their iron stores have returned to normal.
|Iron preparation||Tablet (mg)||Elemental iron (%)||Elemental iron per tablet (mg)||# tablets, 2000 mg total dose||# tablets, 4000 mg total dose|
Alternative sources of iron
Several alternative sources of iron are available (beyond food sources, multivitamins and supplementation). A few of these alternatives include mineral water and cooking solutions (e.g. cast-iron cookware, Lucky Iron Fish™). Individuals are reminded to consult with a physician or pharmacist to determine if an adequate amount of iron is available through these alternatives to sustain their particular situation. As noted above, females and frequent whole blood donors require more iron than the recommended daily intake to maintain adequate iron stores. In healthy individuals, there is no anticipated harm in using these alternatives. However, the efficacy of these alternatives for the prevention and treatment of iron deficiency has not been shown in developed countries.
Approximately two per cent of Canadian adults enable lifesaving treatments for Canadian patients by donating blood. Iron deficiency is a common problem in Canada, particularly in women of child-bearing age. Whole blood donation has a significant impact on iron stores in frequent donors, particularly females. Several measures are necessary to prevent, detect, and treat iron deficiency in donors. Canadian Blood Services has implemented a strategy to mitigate the risk of iron loss through whole blood donation. This strategy includes steps to reduce the frequency of whole blood donations by donors most susceptible to iron deficiency, and to better educate both donors and their physicians about iron depletion associated with whole blood donation. Frequent donors are encouraged to discuss blood donation and possible need for ferritin monitoring and iron supplementation with their physicians. Conversely, when assessing iron deficiency or nonspecific symptoms associated with iron deficiency such as fatigue, physicians should ask their patients about blood donation. Regular blood donors may require temporary iron supplementation to replenish the iron lost from blood donation.
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3. Krayenbuehl PA, Battegay E, Breymann C, Furrer J, Schulthess G. Intravenous Iron for the Treatment of Fatigue in Nonanemic, Premenopausal Women with Low Serum Ferritin Concentration. Blood 2011; 118: 3222-7. https://www.ncbi.nlm.nih.gov/pubmed/21705493.
4. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of Iron Supplementation on Fatigue in Nonanemic Menstruating Women with Low Ferritin: A Randomized Controlled Trial. CMAJ 2012; 184: 1247-54. https://www.ncbi.nlm.nih.gov/pubmed/22777991.
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6. Waldvogel S, Pedrazzini B, Vaucher P, Bize R, Cornuz J, Tissot JD, Favrat B. Clinical Evaluation of Iron Treatment Efficiency among Non-Anemic but Iron-Deficient Female Blood Donors: A Randomized Controlled Trial. BMC Med 2012; 10: 8. https://www.ncbi.nlm.nih.gov/pubmed/22272750.
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12. AABB. Association Bulletin #12-03: Strategies to Monitor, Limit, or Prevent Iron Deficiency in Blood Donors, 2012. http://www.aabb.org/programs/publications/bulletins/Pages/ab12-03.aspx.
13. Brittenham GM. Iron Deficiency in Whole Blood Donors. Transfusion 2011; 51: 458-61. https://www.ncbi.nlm.nih.gov/pubmed/21388389.
14. Popovsky MA. Anemia, Iron Depletion, and the Blood Donor: It's Time to Work on the Donor's Behalf. Transfusion 2012; 52: 688-92. https://www.ncbi.nlm.nih.gov/pubmed/22490271.
15. Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Tobler LH, Simon TL, NHLBI Retrovirus Epidemiology Donor Study I. Iron Deficiency in Blood Donors: The Reds-Ii Donor Iron Status Evaluation (Rise) Study. Transfusion 2012; 52: 702-11. https://www.ncbi.nlm.nih.gov/pubmed/22023513.
16. Goldman M, Uzicanin S, Scalia V, O'Brien SF. Iron Deficiency in Canadian Blood Donors. Transfusion 2014; 54: 775-9. https://www.ncbi.nlm.nih.gov/pubmed/23944738.
17. Newman B. Iron Depletion by Whole-Blood Donation Harms Menstruating Females: The Current Whole-Blood-Collection Paradigm Needs to Be Changed. Transfusion 2006; 46: 1667-81. https://www.ncbi.nlm.nih.gov/pubmed/17002622.
18. Goldman M, Uzicanin S, Osmond L, Scalia V, O'Brien SF. A Large National Study of Ferritin Testing in Canadian Blood Donors. Transfusion 2017; 57: 564-70. https://www.ncbi.nlm.nih.gov/pubmed/27943371.
19. Goldman M, Uzicanin S, Scalia J, Scalia V, O'Brien SF. Impact of Informing Donors of Low Ferritin Results. Transfusion 2016; 56: 2193-8. https://www.ncbi.nlm.nih.gov/pubmed/27306595.
20. Booth AO, Lim K, Capper H, Irving D, Fisher J, McNaughton SA, Riddell L, Keller A, Nowson CA. Iron Status and Dietary Iron Intake of Female Blood Donors. Transfusion 2014; 54: 770-4. https://www.ncbi.nlm.nih.gov/pubmed/23876010.
21. Bryant BJ, Yau YY, Arceo SM, Daniel-Johnson J, Hopkins JA, Leitman SF. Iron Replacement Therapy in the Routine Management of Blood Donors. Transfusion 2012; 52: 1566-75. https://www.ncbi.nlm.nih.gov/pubmed/22211316.
22. Gorlin J. Iron Man Pentathlon or "We Have Met the Enemy and They Is Us!". Transfusion 2014; 54: 747-9. https://www.ncbi.nlm.nih.gov/pubmed/24617626.
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24. Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Vij V, Simon TL, NHLBI Retrovirus Epidemiology Donor Study I. Iron Deficiency in Blood Donors: Analysis of Enrollment Data from the Reds-Ii Donor Iron Status Evaluation (Rise) Study. Transfusion 2011; 51: 511-22. https://www.ncbi.nlm.nih.gov/pubmed/20804527.
25. Baart AM, van Noord PA, Vergouwe Y, Moons KG, Swinkels DW, Wiegerinck ET, de Kort WL, Atsma F. High Prevalence of Subclinical Iron Deficiency in Whole Blood Donors Not Deferred for Low Hemoglobin. Transfusion 2013; 53: 1670-7. https://www.ncbi.nlm.nih.gov/pubmed/23176175.
26. Rigas AS, Sorensen CJ, Pedersen OB, Petersen MS, Thorner LW, Kotze S, Sorensen E, Magnussen K, Rostgaard K, Erikstrup C, Ullum H. Predictors of Iron Levels in 14,737 Danish Blood Donors: Results from the Danish Blood Donor Study. Transfusion 2014; 54: 789-96. https://www.ncbi.nlm.nih.gov/pubmed/24372094.
27. Salvin HE, Pasricha SR, Marks DC, Speedy J., Iron Deficiency in Blood Donors: A National Cross-Sectional Study. Transfusion 2014; 54: 2434-44. https://www.ncbi.nlm.nih.gov/pubmed/24738792.
28. Goddard AF, James MW, McIntyre AS, Scott BB, British Society of G. Guidelines for the Management of Iron Deficiency Anaemia. Gut 2011; 60: 1309-16. https://www.ncbi.nlm.nih.gov/pubmed/21561874.
29. Bryant BJ, Yau YY, Arceo SM, Hopkins JA, Leitman SF. Ascertainment of Iron Deficiency and Depletion in Blood Donors through Screening Questions for Pica and Restless Legs Syndrome. Transfusion 2013; 53: 1637-44. https://www.ncbi.nlm.nih.gov/pubmed/23305102.
30. Cable RG, Brambilla D, Glynn SA, Kleinman S, Mast AE, Spencer BR, Stone M, Kiss JE, National Heart L, Blood Institute Recipient E, Donor Evaluation S, III. Effect of Iron Supplementation on Iron Stores and Total Body Iron after Whole Blood Donation. Transfusion 2016; 56: 2005-12. https://www.ncbi.nlm.nih.gov/pubmed/27232535.