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One question has plagued the field of blood donation for as long as there have been transfusions: Are we harming blood donors by taking blood from them?

Our iron stores are largely self-conserved: Our bodies recycle iron from old red blood cells to make new red blood cells. Iron that’s in use doesn’t tend to exit the body unless a person loses blood, whether through menstruation, bleeding from trauma, illness — or through donation.

While a donor’s body will replace the donated blood volume within 24 hours, the process of replacing the red blood cells could take months. For donors who are low in iron, the process of replacing the lost iron could take over four months, even though donors are eligible for blood donation every 56 days.

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Eldad Hod, associate professor of pathology and cell biology and vice chair of laboratory medicine at Columbia University Irving Medical Center, led a study investigating whether the blood from iron-deficient repeat blood donors continued to meet Food and Drug Administration standards, and whether low-iron status affected the donors’ quality of life or cognitive ability.

In an interview, Hod explained that many regular blood donors know they will be too low in iron to make the cutoff level for donation, so they’ll supplement with iron to build up their red blood cells and cross the threshold just in time to donate again.

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“They live on the edge of anemia so that they can donate blood,” said Hod.

The study, published earlier this month in the journal Blood, focused on frequent blood donors who were low in iron but not anemic. While the terms “anemic” and “low iron” are often used interchangeably, the two are not synonymous; anemia is a condition in which a person does not have enough red blood cells, which can be caused by either iron deficiency or a variety of other reasons.

Additionally, contrary to popular belief, most blood donation centers do not test potential donors for their iron levels prior to donating, as the test needed to evaluate iron levels is too expensive and logistically complicated to carry out at donation sites. Instead, blood donation staff commonly measure hemoglobin levels, which determine whether a person is anemic or not.

“We know that iron is necessary to make red blood cells,” said Nathan Connell, a hematologist at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, who was not involved in the study. “The iron starts to drop. It’s the gas in the gas tank. And before the car runs out, it stops. You have a close-to-empty gas tank. Well, that’s the situation here. Low iron, but the engine hasn’t quite stopped yet,” which would be iron-deficiency anemia.

After the participants in the study donated blood, their blood was screened for its transfusion quality and whether the donors had low iron. Seventy-nine of the study participants who had low iron were then randomized. In a double-blind administration, half were given intravenous iron to correct their iron deficiency, while the other half were given a saline placebo. Four to six months later, the participants were asked to donate again, as well as complete quality of life surveys and cognitive function assessments.

Hod and his team of researchers were surprised to find that there was not a measurable effect on either the blood’s transfusion quality, the iron-deficient donors’ cognitive performance, or their quality of life compared to the iron-replete donors.

“The answer doesn’t fit our preconception, but is actually better for public health because it suggests that what we’re doing is not harming our donors,” said Steven Spitalnik, executive vice chairman for laboratory medicine at Columbia’s department of pathology and cell biology and a co-author on the paper. Further, the results suggest that additional iron level requirements do not have to be added to donor screenings.

A primary concern for the Food and Drug Administration, World Health Organization, and other agencies or groups that manage the blood supply is having both a safe and adequate blood supply. Usually, these entities think about that in terms of infectious disease and from the viewpoint of the recipient, said Connell, but they have an obligation to the donors as well.

“What happens when you get a donor who comes in to donate a unit of blood and then they are turned away because they’re anemic or they’re iron-deficient? What is the mechanism that exists to make sure that that person has that anemia or that iron deficiency addressed?” said Connell. “Because, one, it’s related to their own health, but then allows them to donate again in the future in a safe way. You don’t want to defer people unnecessarily.”

In particular, though there wasn’t an overall difference in blood quality for transfusion, the researchers did find that the quality of blood from women younger than 50 years of age improved following iron repletion, which was not observed in blood donated from women over 50 or from men. Though the researchers say it’s unclear whether this statistical difference is clinically meaningful and needs more study, it’s notable because this population is also the demographic most likely to get turned away from blood donation for low iron, since pre-menopausal people lose iron through menstruation.

Ariela Marshall, director of women’s thrombosis and hemostasis at Penn Medicine, said that instead of just telling would-be donors they can’t donate blood and recommending iron supplements, this is an opportunity to instead say, “It looks like you’re anemic; we suggest that you talk to your doctor about this,” and encourage them to figure out how to address the underlying issue.

Marshall used the illustration of water in a bucket, where the body is the bucket and the water is a person’s blood. “Yes, I can pour in iron; I can refill the bucket,” she said. “But if the bucket has a hole and you’re losing water every single month, then it doesn’t make sense to just keep putting more water in. You’ve got to plug the hole and stop the ongoing process of blood loss.”

“I have many poor patients who’ve struggled with iron-deficiency anemia their whole lives because of heavy periods,” she continued, “and they just keep getting told, ‘Hey, take iron, take iron, take iron.’ Well, that’s great, but that’s not solving the problem.”

Besides the need for more research about iron repletion in blood from younger women, Hod and the other study authors said more research needs to be done about whether the results of this study extend to teenagers. Teenagers, especially high schoolers, make up 10-20% of blood donors, but adolescents need higher amounts of iron for development and it’s currently unclear whether iron depletion in repeat or first-time blood donors from this population is detrimental to them.

Overall, the study’s authors are pleased that their study proved their hypothesis wrong. “We do no harm for people who give blood,” said Gary Brittenham, professor of medicine at Columbia and another co-author on the study, “but we’re doing a great benefit to the people who need it.”

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