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Current standards, donor safety and blood supply

Orieji Illoh, MDOffice of Blood Research and Review

Center for Biologics Evaluation and ResearchFood and Drug Administration

Workshop: Hemoglobin standards and maintaining adequate iron stores in blood donors

November 9, 2011

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Outline Introduction.

Iron stores in blood donors.♦ Iron depletion and deficiency in blood donors.

♦ Interdonation interval.

♦ Previous public discussions.

Workshop objectives.

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Introduction

Consideration of the balance between donor safety and blood supply.

Donor safety issues. Iron loss following frequent blood

donation.

Blood supply issues. Impact of any changes interdonation

interval on blood supply.

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Why address iron loss in blood donors?

Improve donor safety.

Allow adequate time for iron recovery.

Decrease the incidence of iron deficiency among blood donors.

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Iron depletion and deficiency

Iron loss occurs following blood donation.

Frequent donations may lead to iron deficiency with or without anemia.

Hemoglobin testing is not an accurate measure of iron stores.

Need to consider strategies to mitigate iron deficiency in blood donors.

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Effects of iron deficiency Adverse effects include anemia, fatigue,

restless leg syndrome, possible cognitive impairment, depression, and anxiety.

There are reports suggesting a beneficial effect of low iron stores in males undergoing repeated phlebotomy. ♦ Favorable lipoprotein profile compared to non

blood donors♦ Lower risk of cardiovascular disease♦ Possible reduction of iron-induced oxidative stress van Jaarsveld et al. Atherosclerosis. 2002 Apr;161(2):395-402. Salonen et al. Am. J. Epidemiol. 148 (1998):445–451.

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Mitigation of Iron loss in blood donors

Allow more time for recovery of iron stores.

♦ Interdonation interval

Test for iron stores.♦ e.g. ferritin testing

Iron replacement♦ Provide iron supplements

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Interdonation interval

An appropriate interdonation interval should ensure donor safety by allowing time for adequate red blood cell recovery.

21CFR 640.3(b)♦A person may not serve as a source of

Whole Blood more than once every 8 weeks ~ 6 donations/year

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Increasing the interdonation interval

May decrease the risk of iron deficiency.

May allow more time for iron recovery. May decrease future donor deferral for

low hemoglobin.

Will adversely affect the blood supply.

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Effect on blood availability

Increasing the interdonation interval may negatively affect the supply of the

following: Red blood cells especially O negative RBCs

and other rare phenotypes. Collections obtained by apheresis.

♦ Double red blood cells

♦ Other blood components

Availability of donors for reagent manufacturers.

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International standards

Single hemoglobin standard: 12.5g/dL

Country Hb-male g/dL

Hb-female g/dL

Donation frequency

United States 12.5 12.5 56 days

Canada 12.5 12.5 56 days

Switzerland 12.5 12.5 Women, 3x/yr, Men 4x/yr

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International standards

Gender specific hemoglobin standard : Males 13.0g/dL, Females 12.0g/dL

Country Hb-male (g/dL)

Hb-female (g/dL)

Donation frequency

France 13.0 12.0 56 days; women 4x/yr, men 6x/yr

Australia 13.0 12.0 84 days

Israel 13.0 12.0 90 days; 4x/yr

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International standards

Gender specific hemoglobin standard : Males 13.5g/dL, Females 12.5g/dL

Country Hb-male g/dL

Hb-female g/dL

Donation frequency

Europe: Council of Europe

13.5 12.5 56 days; women 4x/year, men 6x/yr

United Kingdom 13.5 12.5 84 days acceptable, but recommend 112 days

Scotland 13.5 12.5 84 days (3x/yr)

Germany 13.5 12.5 56 days; women 4x/yr, men 6x/yr

Sweden 13.5 12.5 84 days; women 3x/yr, men 4x/yr

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International hemoglobin standards

Gender specific hemoglobin standard : Males 13.0g/dL, Females 12.5g/dL or 11.5g/dL

Country Hb-male g/dL

Hb-female g/dL

Donation frequency

Brazil 13.0 12.5 Women 90 days, 3x/yr, Men 60 days, 4x/yr

Hong Kong 13.0 11.5 Women 3x/yr, men 4x/yr

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Previous public discussions

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Public workshop Workshop: “Maintaining Iron Balance in Women

Blood Donors of Child Bearing Age.” June 8, 2001

Discussed Iron deficiency in female premenopausal blood donors.

♦ Medical issues related to iron replacement♦ Iron replacement and possible protocols

Recommended implementation of a research program on iron replacement.

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FDA Proposed Rule (November 2007)

FDA asked for comments and supporting data on:

Increasing the interdonation interval.

Changing the hemoglobin or hematocrit levels to 12.0g/dL or 36%, as acceptable minimal values for female allogeneic donors.

The possibility of adverse effects if a minimum of 12.0g/dL or hematocrit of 36% is used for females.

The possibility of adverse effects if a minimum of 12.5g/dL or hematocrit of 38% is maintained for males.

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Representative comments to the Proposed rule

Wait for results of REDS II study on iron status in blood donors .

Agree with proposal to lower hemoglobin standard in women to 12.0g/dL.

♦ Hemoglobin down to 12.0 g/dL is normal for females

♦ Enormous potential to improve the blood supply

Disagree with proposal to lower hemoglobin standard in women to 12.0 g/dL.

♦ Does not have any positive benefit to the donor

♦ May make women susceptible to iron deficiency or anemia

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BPAC: September, 2008

Topic: Iron Status in Blood DonorsCommittee members agreed that iron

depletion in blood donors is a concern.Discussed testing for iron status in the

donor setting .Discussed alternative strategies to

mitigate iron depletion.♦ Iron supplementation, dietary recommendations

♦ Changing Hb/hct acceptance standards

♦ Modification of interdonation interval

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Advisory Committee for Blood Safety and Availability: December, 2008

Include in consent forms: ♦ The effects of repeat donation on the donor

population.

♦ The gender specific effects of iron deficiency on donors.

♦ The effects of collecting blood from anemic men using current donation thresholds.

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BPAC meeting, July 27, 2010

Committee recommendations Await final analysis of study on blood donors

before considering any changes to the interdonation interval.

Committee votes 10-0 to increase hemoglobin requirement for

male donors. 9-0 (one abstention) against a decrease in

hemoglobin requirement for female donors.

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Key pointsDonor safety issues

♦ Iron deficiency due to frequent donations.

Blood availability issues♦ Impact on blood supply if interdonation

interval is changed.

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Workshop objectives- todayDiscuss recent studies on iron status of

blood donors.

Discuss strategies to maintain iron balance in blood donors.

♦ Review testing methods available for iron stores.

♦ Review recent studies on iron supplementation in blood donors.

♦ Discuss how changing the interdonation interval could affect blood availability.