Blood Donors: FDA Meets on Iron Management, Teen Issues

Troy Brown, RN

November 18, 2016

The Blood Products Advisory Committee of the US Food and Drug Administration (FDA) met yesterday to discuss acceptable strategies for iron management in blood donors and adverse reactions related to blood donation in adolescent donors.

The committee voted that in the absence of effective iron supplementation, available scientific evidence supports the need for routine monitoring of iron stores in all blood donors (9 yes, 5 no, 1 abstention); frequent blood donors, both male and female (14 yes, 1 no); and premenopausal female donors (14 yes, 1 abstention).

The panel voted that with effective iron supplementation, available scientific evidence does not support the need for routine monitoring of iron stores in all blood donors (4 yes, 10 no, 1 abstention) but does support the need for routine monitoring in frequent blood donors, both male and female (11 yes, 4 no) and premenopausal female donors (10 yes, 4 no, 1 abstention).

The committee voted overwhelmingly (14 yes, 1 no) that available scientific evidence confirms that iron supplementation in blood donors mitigates iron deficiency.

Iron Supplementation Important

The votes followed discussion of several studies. The Strategies to Reduce Iron Deficiency Study (STRIDE) found that once-daily administration of 19-mg iron pills for a period longer than 60 days is as effective as administration of 38-mg iron pills for mitigation of iron deficiency in blood donors. The study also showed that giving donors information about their iron status (ferritin results) and offering them a choice between iron supplementation and delayed donation is also an effective strategy for mitigating iron deficiency.

Additionally, the STRIDE study found that in frequent donors, iron deficiency mitigation strategies improved the donor's hemoglobin (Hb) status and that continued donation without mitigation of iron losses progressively worsens iron deficiency.

The panel voted by a large margin (12 yes, 2 no, 1 abstention) that available scientific evidence confirms that iron supplementation in blood donors improves Hb recovery.

The Hemoglobin and Iron Recovery Study (HEIRS) found that, compared with no supplementation, low-dose iron supplementation reduced time to 80% Hb recovery of the postdonation decrease in Hb concentration in iron-depleted donors and iron-replete donors with normal Hb levels. The researchers also found that the iron supplementation increased total body iron levels after blood donation, particularly in iron-depleted donors. Most of the total body iron recovery occurred in the first 8 weeks after blood donation.

It can be difficult to ensure adherence to iron supplementation, in part because of side effects, including constipation. Patients do not always understand how important it is to take iron supplements. One committee member said that even partial adherence to iron supplementation can benefit patients.

"In our patient population, because adherence is such an issue, you can actually see that even [in] patients who don't take iron every day like you tell them to, or three times a day like you tell them to, there is improvement in their iron levels, in their hemoglobins, in their ferritins," voting member Meera B. Chitlur, MD, director, Hemophilia Treatment Center and Hemostasis Program and Special Coagulation Laboratory, professor of pediatrics, Wayne State University; Division of Hematology/Oncology, Children's Hospital of Michigan, Detroit, said.

"[E]ven though we don't expect to see 100% adherence, there's definitely a benefit to getting it, even if it's not as perfect as we would like it to be," she added.

The REDS II Donor Iron Status Evaluation Study (RISE) found that measuring ferritin levels and giving iron supplements was feasible in a blood center and that adherence with iron supplementation was high. The study also found, though, that mailing iron supplements to donors can be "cumbersome and expensive, and that alternative methods to providing iron should be considered," according to an FDA briefing document.

"I think every donor that is seen who has potential should have a letter to their physician that talks about the critical importance, because I don't think they know," voting member Margaret V. Ragni, MD, MPH, professor, Department of Medicine, University of Pittsburgh Pennsylvania, said.

The panel widely agreed that increasing the minimum interdonation intervals for men and women without monitoring of iron stores is not an effective strategy for preventing iron deficiency.

The committee voted unanimously that the available scientific evidence relating to iron deficiency in adolescent blood donors suggests that teenage blood donors are susceptible to developing iron deficiency.

American Association of Blood Banks Proposed Procedure for Collection of Blood From Female Donors With Hg Values Between 12.0 and 12.5 g/dL

A Canadian study found that 90% of female donors with Hg levels less than 12.5 g/dL had low or absent iron stores (absent, ferritin <12 μg/L; low, ferritin 12 - 24 μg/L) compared with 50% in donors with Hg levels greater than 13.0 g/dL and 67% in those with Hg levels between 12.5 and 12.9 g/dL (13).

The committee discussed two proposed procedures for ensuring donor safety for collection of blood from female donors with Hg values of 12.0 to 12.4 g/dL or a hematocrit value between 36 and 38:

Proposal A – ferritin testing strategy:

  • Collect unit and predonation blood sample for ferritin measurement before availability of ferritin test results.

  • Give iron supplementation.

  • Defer donation for 16 weeks for women with low ferritin levels.

Proposal B – extended deferral, no ferritin testing:

  • Blood may be collected from a donor who is already iron deficient.

  • Defer blood donation for 6 months.

  • Give iron supplementation.

Extended deferral allows for iron recovery; however, this may not be adequate in those who are not taking iron. Iron supplementation should ensure reasonable donor adherence.

"I find option B without ferritin testing to be completely unacceptable from everything we have heard this morning. These are volunteers coming in to give a gift, and there is a 50% likelihood that you are going to be doing them harm, and no one can guarantee that the subject takes the iron...or even gets the message, because a lot of subjects don't," said voting member and acting chair Susan F. Leitman, MD, director, Medical Research Scholars Program, Office of Clinical Research Training and Medical Education, National Institutes of Health, Bethesda, Maryland. "So without knowledge of what you are doing with such a high risk and with consequences of that risk, I find that not an acceptable alternative."

"If you allow collection without knowledge of the iron stores, then in effect, what you're saying is that it's acceptable to take blood from someone who's iron deficient and make them more iron deficient. Both proposals permit the collection of blood without further evaluation.... I think that's a concern," temporary voting member Gary Brittenham, MD, James A. Wolff Professor of Pediatrics and professor of medicine, Columbia University College of Physicians and Surgeons, Children's Hospital of New York, New York City, said.

Mitigation of Adverse Reactions Related to Blood Donation

Blood donation is mostly safe. However, approximately 2% to 6% of donors will experience some kind of complication after donation. Most of these are minor hematomas or mild vasovagal reactions.

Risk factors include young age, female sex, first time donation, and low estimated blood volume. Presyncopal symptoms, including dizziness, lightheadedness, and pallor, occur in 5% to 10% of donors younger than 19 years, compared with 2% to 5% of all donors.

An American Red Cross study found that 16- and 17-year-old donors were 2.5 times more likely to experience syncope-related injuries compared with 18- and 19-year-olds and were 14.5 times more likely than donors aged 20 years or older.

The committee discussed the effectiveness of several mitigation measures: applied muscle tensing or leg lifting exercises during donation; having the donor drink 500 ml of water immediately before donating; and predonation preparation to explore the patient's fears or anxieties and providing the patient with coping strategies.

The committee voted unanimously that the available evidence indicates that adverse reactions and injuries after blood donation in teenage donors are notable enough concerns to require intervention.

The committee voted unanimously that the available evidence supports applying donor-specific selection criteria, such as estimated blood volume less than 3500 mL, as a means to mitigate donor reactions.

The committee voted by a wide margin (10 yes, 4 no, 1 abstention) that the available data indicate that specific measures, such as applied muscle tension to mitigate adverse reactions to blood donation, are effective.

The committee widely agreed that blood donation should not be limited to those aged 18 years and older.

The participating committee members have disclosed no relevant financial relationships.

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