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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 8, 2011

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Outline

Introduction.

Hemoglobin standards.♦ Regulatory history

♦ Considerations to adjusting hemoglobin standards

♦ Previous Public discussions

Workshop objectives.

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Introduction

Consideration of the balance between donor safety and blood supply

Donor safety issues. Hemoglobin standards

Blood supply issues. Impact of any changes in hemoglobin

standards on blood supply

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Why adjust hemoglobin standards?

Establish ranges within physiologic norms.

Avoid donations from male donors in “anemic” range.

Allow more donations from female donors in “normal” range.

♦ ~95% of hemoglobin donor deferrals occur in women.

♦ Hemoglobin deferrals have a negative impact on future blood donations.

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Hemoglobin measurement

Test characteristics.♦ Simple, point of care test.

♦ Testing methods differ and are affected by physiologic and operator variables.

♦ Quantitative methods reliably measure hemoglobin within 0.2g/dL to 0.5g/dL.

Relationship to donor health.♦ Used as an indirect measurement of iron status.

♦ Studies show that hemoglobin is not a good indicator of iron stores.

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Hemoglobin measurement

Current requirement: 21CFR 640.3(b)(3)♦Blood hemoglobin level no less than 12.5g/dL

or hematocrit no less than 38% in both male and female allogeneic donors.

Purpose♦Ensure donor safety.♦Ensure collection of a potent product.

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Chronology of FDA requirements for hemoglobin standards

The threshold of 12.5g/dL was established in 1958 and has not changed.

♦ Gender specific hemoglobin standards were proposed in the past but never finalized.

There have been discussions about changing hemoglobin standards in the past.

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Considerations for Changing Hemoglobin Acceptance Standards

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Definitions of anemiaGroup Hemoglobin levels below

which 5% of the normal subjects in the population will be found (g/dL)

White men20 -59

13.7

Black men20-59

12.9

White women20-49

12.2

Black women20-49

11.5

Blood. 2006 Mar 1;107(5):1747-50

NHANES III and Scripts –Kaiser databases

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NHANES II data: Hb concentrations in men 18 to 44 years of age. ( ) Caucasian men; (░) African American men.◆

Hemoglobin distribution in men

Transfusion. 2006 Oct;46(10):1667-81.

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NHANES II data: Hb concentrations in women 18 to 44 years of age. ( ) Caucasian women; (░) African American women.◆

Hemoglobin distribution in women

Transfusion. 2006 Oct;46(10):1667-81.

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Adverse effects At a minimum hemoglobin of 12.5g/dL (hct

38%) for males♦Underlying medical conditions may not be

addressed

♦Worsening of existing iron deficiency?

At a minimum hemoglobin of 12.0g/dL (hct 36%) for females♦ Iron deficiency?

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Australian blood donors: Iron storage status of donors with different predonation

thresholds

Total donor population iron deficient (%)

ARCBS Hb threshold from 1/1/04

Males ≥ 12.6g/dL 6.2

Females ≥ 11.8g/dL 22.0

ARCBS Hb threshold from 1/1/05

Males ≥ 13.0g/dL 6.0

Females ≥ 12.0g/dL 20.6

Dev Biol (Basel). 2007;127:137-46.

1535 males 1487 females

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International hemoglobin standards

Single hemoglobin standard: 12.5g/dL

Country Hb-male g/dL

Hb-female g/dL

United States 12.5 12.5Canada 12.5 12.5Switzerland 12.5 12.5

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International hemoglobin standards

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

Country Hb-male (g/dL)

Hb-female (g/dL)

France 13.0 12.0Australia 13.0 12.0Israel 13.0 12.0

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International hemoglobin standards

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

Country Hb-male g/dL

Hb-female g/dL

Europe: Council of Europe

13.5 12.5

United Kingdom 13.5 12.5Scotland 13.5 12.5Germany 13.5 12.5Sweden 13.5 12.5

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International hemoglobin standards

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

Country Hb-male g/dL

Hb-female g/dL

Brazil 13.0 12.5Hong Kong 13.0 11.5

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Effect on blood availability - Males

There will be a loss of male blood donors if the hemoglobin threshold is raised.

Loss of male African American donors.♦ Special phenotype RBCs required for sickle cell

patients.

May impact availability of plasma from male donors.

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Effect on blood availability - Females

If the standard is dropped to 12.0g/dL, there may be gain of female donors.

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Previous public discussions

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FDA Proposed Rule (November 2007)

FDA asked for comments and supporting data on:

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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Blood Products Advisory Committee: September, 2008

Topic: Iron Status in Blood Donors.

Discussed alternative strategies to mitigate iron depletion.

♦Changing Hemoglobin/hematocrit acceptance standards.

♦ Iron supplementation, dietary recommendations.

♦Modification of interdonation interval.

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Advisory Committee on Blood Safety and Availability - December 2008

Recommendations FDA should reconsider donor hemoglobin

acceptance values. Adopt different, gender-appropriate

acceptance values The current single value (12.5 g/dL) permits

acceptance of a significant number of "anemic" males while excluding many normal females.

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BPAC meeting, July 27, 2010

Committee votes 10-0 to increase hemoglobin requirement for

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

hemoglobin requirement for female donors.

Committee recommendations Await final analysis of study on blood donors

before considering any changes to the interdonation interval.

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Key points

Donor safety issues.♦ Blood collection from anemic

males with current hemoglobin standard.

Blood availability issues.♦ Potential gain of female blood

donors.

♦ Potential loss of male blood donors.

http://www.anemia.org

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Workshop objectives- today Obtain current information on the

relationship between donor hemoglobin standards and donor safety.

Discuss the effect of hemoglobin standards on blood availability.

Discuss hemoglobin measurement methods in blood donors.