After years of suspecting a problem, blood collection groups now have sufficient evidence to say that the eight-week minimum interval between blood donations is causing many donors to develop iron deficiency.

The American Association of Blood Banks is now drafting a bulletin to blood collection centers in which it will acknowledge that iron depletion is a problem for frequent blood donors, and outlying potential steps centers can take to mitigate the impact.

“It’s clear that we do deplete donors of iron, and that there are some donors that may be harmed by that,” said Dr. Richard Benjamin, medical director of the American Red Cross and part of the workgroup writing the bulletin. “If you give more than three, four, five times a year, you are likely to be depleting your iron. What is unclear is how harmful that is.”

Iron is a key component in red blood cells, which carry oxygen to the muscles. When iron stores drop, oxygen supply is reduced, leaving individuals feeling tired or lacking in energy.

The missive is expected to outline four steps that blood collection centers could take to protect donors from iron depletion: extending the interval between donations, measuring iron levels more directly with a blood test, providing frequent donors with iron tablets to replace lost iron and educating donors about iron deficiency and replacement strategies.

Blood donors are currently tested for low hemoglobin levels, but recent studies have shown the hemoglobin finger-stick test is a poor indicator of a person’s overall iron stores. Hemoglobin is the iron-containing protein in red blood cells, but about 25 percent of the body’s iron is stored in the protein ferritin. Unlike free iron, ferritin is not toxic to the cells.

Last year, researchers published the results of the most comprehensive study of iron deficiency in blood donors to date. The results were surprising.

Among frequent donors — defined as women who donate more than three times a year and men who donate more than four times — two-thirds of women and half of men where iron deficient, despite having passed the finger-stick hemoglobin test.

According to the Centers for Disease Control and Prevention, among the general population, about 2 percent of U.S. men and 3 percent of U.S. women are iron deficient.

“The unavoidable conclusion is present blood collection practice fails to protect committed blood donors from the iron deficiency,” Dr. Gary Brittenham, a pediatric hematologist, wrote in an editorial on the study findings in the journal Transfusion last year.

Blood donation experts have long suspected the current standards for donating blood may lead to iron depletion if not outright deficiency in donors, but other than anecdotal reports, had little hard data on which to base decisions.

A second study published last month by the National Institutes of Health Department of Transfusion Medicine found that 49 percent of women and 39 percent of men who passed finger-stick hemoglobin tests had low iron stores. Combined, those studies are prompting the Red Cross and other blood collection centers to look at making changes.

“Do we have enough knowledge to make a change today? That answer’s got to be yes,” Benjamin said.

Changing the rules

While blood donation standards are set by the FDA, collection centers can adopt stricter rules on their own. One option would be to increase the minimum time between donations. The FDA has set that minimum interval at 56 days, allowing donors to give blood more than six times a year. The U.S. and Canada have the shortest duration of any country. The U.K., for example, requires a wait of 112 days, although the nation’s National Health Service recently launched a study to determine whether that interval could be shortened.

Benjamin said, however, that increasing the minimum interval in the U.S. could cut the overall blood supply by 5 to 10 percent.

Another option would be to improve the testing for iron depletion by measuring ferritin levels in the bloodstream. That would be more complicated to do at donation sites. Results of the test would not be available prior to the donation, meaning blood centers would have to notify donors of their low iron status after the fact. Those donors could then seek help from their doctors to restore their iron stores.

That’s not unlike what now happens with blood that tests positive for HIV or hepatitis. The testing would also add additional costs to the process, and there is no ferritin test approved by the FDA for donor screening.

Blood centers are considering handing out iron tablets to frequent donors. But if that was done in the absence of ferritin testing, it could results in some donors getting more iron than needed.

FDA officials have also been asking their advisors about the possibility of changing the hemoglobin cutoffs to donate. Currently, both men and women must have a hemoglobin score of at least 12.5 grams per decaliter to donate. Many consider that cutoff to be too low for men, and some believe it is too high for women. That could mean many women with normal iron stores are being deferred while at the same time, men who are borderline anemic are allowed to donate.

But while blood collection organizations recognize that iron stores are being depleted with the current donation protocols, they are less sure that patients are experiencing any harm.

“We really have no evidence, whether symptomatology or good clinical evidence, that we’ve done harm,” Benjamin said. “It’s a theoretical construct.”

The NIH study did find that iron-deficient donors had higher rates of restless leg syndrome or a condition known as pica, which is characterized by a desire to eat non-nutritive substances, such as chewing ice. Donors who develop anemia can also feel fatigued or lethargic.

Dr. Celso Bianco, executive vice president of America’s Blood Centers, fears that moves to protect donors from uncertain harm could also affect the supply of blood needed to save lives.

“We want to do well with the donors, but on the other hand, we are afraid that if you just go for a number in the cutoff in hemoglobin, we are going to create some issues and we may not resolve the problem,” Bianco said.

A change in the hemoglobin cutoff, he says, could affect the number of African-American donors who have a higher prevalence of certain kinds of blood types needed to treat conditions like sickle cell anemia.

“Even among Caucasians, we are all after the universal donor, the O-negative, for red cells, and so those are the donors that get more calls from the centers to go and donate,” Bianco said. “What is the impact of reducing the frequency of donation by those individuals?”

While replacing the iron lost though frequent blood donations could be an option that doesn’t affect the supply of blood, Bianco expressed concerns that handing out iron tablets could mask the symptoms of other conditions not caused by blood donation.

“For instance, among males, (with) colon cancer or even hemorrhoids, the way you are going to find out that a person has the problem is because they have a lower level than expected of hemoglobin and that will trigger a lot of action by the physician searching for a cause,” he said.

Patient harm

But blood collection officials also acknowledge they’ve heard plenty of cases of patients whose doctors ordered test after test searching for the cause of blood loss, the most common cause of iron deficiency, without considering the impact of blood donation.

Joe Weirzba, 63, of Bend, has been donating blood since he was 18, prompted by a classmate who had hemophilia. While a health care administrator on the Oregon Coast, he donated every time a blood drive came to town, about two to three times a year. But once he and his wife, Shelly, moved to Bend two years ago, he could donate every eight weeks.

After his 10th donation at the minimum interval, a blood test during an annual physical in July showed his ferritin levels were well below normal. The low end of the normal ferritin level for men is between 12 and 18 nanograms per milliliter of blood. Wierzba’s levels were in the single digits.

“That started a process with the doctor and the first part of that was kind of scary,” he recalled. “The first step in the algorithm or standard of care is, this guy is losing blood, so where is it coming from?”

His doctors recommended a colonoscopy and endoscopy to search for possible internal bleeding or colon cancer.

Wierzba asked his wife, a physician assistant, whether his low iron levels could be the result of blood donation.

At first she discounted the notion. After all, there are set standards to ensure donors don’t donate too often. But upon researching the issues, she uncovered dozens of case reports suggesting her husband’s case was hardly unique.

Wierzba stopped donating blood and by December, his ferritin levels had rebounded to normal levels.

“The doctor said this could be cancer,” he recalls. “We’d been in health care really long and this was a real awakening how tenuous all of this is.”

Benjamin said that sort of cascade of events is not uncommon.

“We do have a lot of anecdotes, donors coming in and saying, ‘I went to my doctor and they saw I was anemic. I told him I was a blood donor but he ignored me, and said, ‘you might have colon cancer, so we’d better do $10,000 worth of tests,’” he said. “That’s where we’ve failed.”

Benjamin said at a minimum, Red Cross centers will work to do a better job of educating patients about the risk of iron depletion and ways they can protect themselves, whether through diet and iron replacement or by waiting longer to donate if they see any of the warning signs of iron depletion.

“If you are a frequent donor or a female of childbearing age, just eating a steak once a month is not going to replace the iron,” Benjamin said. “You should seriously consider taking some iron supplementation.”

Dr. Barbara Bryant, a pathologist with the University of Texas Medical Branch, has been running perhaps the longest study of iron replacement with blood donors so far. Working with the Department of Transfusion Medicine at NIH, she developed a protocol for iron replacement and tested it in the first long-term study in blood donors. The study identified donors who had been deferred due to low hemoglobin, tested their blood for ferritin levels and then provided them with a 60-day supply of iron tablets.

“We actually watched the laboratory values as they continued to donate blood,” she said. “There was a correction of the iron depletion or deficiency that we had observed. As you continue to donate, you basically absorb the amount of iron you need.”

Bryant said that 68 percent of the test subjects given supplements took the full supply, and all of them returned to the normal range of iron stores. The researchers also found that while in their general donor population donors averaged 1.3 donations per year, those that were in the study were able to donate 1.9 times a year.

“It’s something that makes sense,” she said. “It’s relatively easy to do and it’s safe, with good results.”

It’s a protocol that donors could implement on their own as well. Benjamin recommends that even frequent donors check with their doctors before starting to take iron supplements.

Bianco said that while there is concern about iron stores, he hopes that donors remember the importance of blood donation.

“Most people fall with in the normal category and have reasonable stores,” he said. “If people feel they are very tired, if they are pale, if their hemoglobin is too close to the cutoffs, they could wait a little bit longer between donations.”

Donors at America’s Blood Centers donate on average 1.7 times a year, he said. Even if individuals donated twice a year, they could increase the current supply of blood without putting their iron stores at risk.

“Encourage them to donate,” he said, “but to pay attention to their bodies. If they have a good diet, if they have a healthy set of habits, they will do well.”