Iron Deficiency and Blood Donation: Links, Risks and Management

Figures & data

Table 1 Studies of Oral or Parenteral Iron Supplementation in Blood Donors

Authors	Study Design	Iron Products Used	Main Study Outcomes
Kiss JE, et al^Citation53	Randomized	Ferrous gluconate 37.5 mg/day vs no iron for 168 days post donation of 500 mL of whole blood.	Recovery of iron stores in participants who received supplements took a median of 76 days; for participants not taking iron, median recovery time was 168 days (p <0.001). Without iron supplements, 67% of participants did not recover iron stores by 168 days.
Gordeuk V, et al^Citation54	Randomized double-blind	Carbonyl iron 100 mg orally vs no iron at bedtime for 56 days after phlebotomy	At day 56, estimated iron absorption was sufficient to replace iron in 85% of those receiving carbonyl iron but in only 29% of those taking placebo (p < 0.001)
Marks DC, et al^Citation55	Randomized, double-blind, placebo- controlled	Carbonyl iron 45 mg daily vs placebo for 8-weeks post-donation	The mean Hb level in the carbonyl iron group (134.6 ± 8.7 g/L) was significantly higher than in the placebo arm (130.0 ± 9.9 g/L; p < 0.001), significantly improving eligibility to donate at Week 12
Birgegård G, et al^Citation56	Randomized	Iron sucrose 200 mg IV versus 20×100 mg tablets of oral iron sulphate (1 tablet/day) after each blood donation for 1 year	The IV iron group increased storage iron to a greater extent than the oral iron group after 12 months (p=0.0043)
Bryant BJ, et al^Citation57	Single arm study	Deferred donors and iron-deficient control donors were given 60 tablets containing 325mg ferrous sulfate (1tablet/day for 60 days). Another 60 tablets were dispensed at all subsequent visits	Iron-depleted or -deficient donors taking iron showed normalization of iron-related laboratory parameters, even as they continued to donate
Krayenbuehl PA, et al^Citation58	Randomized, double-blind, placebo-controlled	Iron sucrose IV 800 mg vs intravenous placebo	In patients with baseline ferritin ≤ 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (p = 0.005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (p=0.03)
Gybel-Brask M, et al^Citation59	Randomized double blind, placebo-controlled	First-time female blood donors randomized 1:1 to iron isomaltoside 1000 mg IV vs placebo	The increase in Hb was significantly higher for iron isomaltoside compared with placebo right before both the second (p = 0.0327) and the third blood donation (primary endpoint, p < 0.0001)
Cable RG, et al^Citation60	Randomized	Donors randomized to oral ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation	At 24 weeks, total body iron in donors taking iron increased by 281 mg (95% CI, 223.4–338.6 mg) compared to before donation, while in donors not on iron decreased by 74.1 mg (95% CI, −112.3 to −35.9; p < 0.0001, iron vs no iron)
Chiamchanya N^Citation61	Randomized, three arm study	Oral ferrous fumarate 200 mg/day (group I) vs ferrous fumarate 200 mg/day+ascorbic acid 100 mg/day (group II) vs ferrous fumarate 200mg/day+ascorbic acid 500 mg/day (group III)	The recovery times of MCV, MCH, and MCHC to before blood donation levels in groups II and III were similar (0.5 months in every value), which was more rapid than in group I (> 3, 3, and 1 month, respectively) (p < 0.001)
Drexler C, et al^Citation62	Randomized, two arm study	Donors randomized to a single dose of ferric carboxymaltose IV or oral ferrous fumarate (100 tablets of 100 mg [10 tablets per week] for 10 weeks	Median TS and ferritin were significantly higher in the IV iron group (27% vs 21%, p < 0.001 and 105 vs 25 ng/mL (p < 0.001), while median Hb levels were comparable (IV, 13.6g/dL vs oral 13.6 g/dL)
Mast AE, et al^Citation63	Randomized, five arm study	Three double-blinded arms provided 60 once-daily pills after each donation (38 mg, 19 mg, or 0 mg of iron) and two single-blinded arms provided iron status (ferritin) information or no information letters after each donation	Prevalence of ferritin <12 or < 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19mg or 38 mg of iron; iron status letter). Improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups
Radtke H, et al^Citation64	Randomized placebo-controlled study	Donors assigned to treatment with either 40 mg, 20 mg, or 0 mg per day of elemental iron as ferrous gluconate for a period of 6 months, during which one unit of whole blood was collected on 4 occasions in males or 3 in females	Daily doses of either 40 mg or 20 mg of ferrous gluconate adequately compensated for iron loss in males, who gave blood at 2-month intervals, but did not result in a positive iron balance or an increase in storage iron, while in females who donated at 3-month intervals, the same daily doses restored the iron balance and increased storage iron
Radtke H, et al^Citation66	Randomized, two arm study with placebo phase	Donors were randomly assigned to receive 100 mg of ferrous iron or placebo daily. Group A received iron capsules after the first three donations, and Group B after the second three donations	Mean serum ferritin concentration decreased after each donation in the placebo phase of both treatment groups, but it remained mostly constant during the iron phase in Group A, and even increased during the iron phase in Group B
Macher S, et al^Citation67	Randomized, controlled, single-centre trial	Ferric carboxymaltose 1000 mg IV as a single dose or oral iron supplementation (100 capsules of 100 mg iron fumarate, 1 capsule/day for 100 days)	Significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p < 0.001). Significant decrease in headaches, dyspnea, dizziness, and palpitations (p < 0.05) with no difference between intravenous vs oral iron and clinical outcome

Abbreviations: Hb, hemoglobin; CI, confidence intervals; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; TS, transferrin saturation; IV, intravenous; RLS, restless leg syndrome.

Kiss JE, Brambilla D, Glynn SA, et al. Oral Iron supplementation after blood donation: a randomized clinical trial. JAMA. 2015;313(6):575. doi:10.1001/jama.2015.119

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Gordeuk V, Brittenham G, Bravo J, Hughes M, Keating L. Prevention of iron deficiency with carbonyl iron in female blood donors. Transfusion. 1990;30(3):239–245. doi:10.1046/j.1537-2995.1990.30390194345.x

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Marks DC, Speedy J, Robinson KL, et al. An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial. Transfusion. 2014;54(3pt2):780–788. doi:10.1111/trf.12464

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Birgegård G, Schneider K, Ulfberg J. High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron. Vox Sang. 2010;99(4):354–361. doi:10.1111/j.1423-0410.2010.01368.x

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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(7):1566–1575. doi:10.1111/j.1537-2995.2011.03488.x

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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(12):3222–3227. doi:10.1182/blood-2011-04-346304

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Gybel-Brask M, Seeberg J, Thomsen LL, Johansson PI. Intravenous iron isomaltoside improves hemoglobin concentration and iron stores in female iron-deficient blood donors: a randomized double-blind placebo-controlled clinical trial. Transfusion. 2018;58(4):974–981. doi:10.1111/trf.14521

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Cable RG, Brambilla D, Glynn SA, et al. Effect of iron supplementation on iron stores and total body iron after whole blood donation. Transfusion. 2016;56(8):2005–2012. doi:10.1111/trf.13659

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Chiamchanya N. Rapid recovery time of hemoglobin level in female regular blood donors with ferrous fumarate and high dose of ascorbic acid supplement. J Med Assoc Thai. 2013;96(2):165–171.

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Drexler C, Macher S, Lindenau I, et al. High-dose intravenous versus oral iron in blood donors with iron deficiency: the IronWoMan randomized, controlled clinical trial. Clinical Nutrition. 2020;39(3):737–745. doi:10.1016/j.clnu.2019.03.025

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Mast AE, Bialkowski W, Bryant BJ, et al. A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors. Transfusion. 2016;56(6pt2):1588–1597. doi:10.1111/trf.13469

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Radtke H, Tegtmeier J, Röcker L, Salama A, Kiesewetter H. Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study. Transfusion. 2004;44(10):1427–1432. doi:10.1111/j.1537-2995.2004.04074.x

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Radtke H, Mayer B, Röcker L, Salama A, Kiesewetter H. Iron supplementation and 2-unit red blood cell apheresis: a randomized, double-blind, placebo-controlled study. Transfusion. 2004;44(10):1463–1467. doi:10.1111/j.1537-2995.2004.04045.x

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Macher S, Herster C, Holter M, et al. The effect of parenteral or oral iron supplementation on fatigue, sleep, quality of life and restless legs syndrome in Iron-deficient blood donors: a secondary analysis of the IronWoMan RCT. Nutrients. 2020;12(5):1313. doi:10.3390/nu12051313

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