Iron Status in Blood Iron Status in Blood DonorsDonors

Barbara J. Bryant, MDBarbara J. Bryant, MD

University of Texas Medical BranchUniversity of Texas Medical Branch

Galveston, Texas Galveston, Texas

andand

Department of Transfusion MedicineDepartment of Transfusion Medicine

National Institutes of HealthNational Institutes of Health

Bethesda, MarylandBethesda, Maryland

Iron Deficiency in Blood Donors

Iron deficiency in 1st time and repeat blood donors is a challenge in transfusion medicine

Iron is an essential element lost with each blood donation 242 17 mg for men 217 11 mg for women

Normal iron stores 1000 mg men 350 mg women

Iron Deficiency in Blood Donors In order for a donor to

compensate for iron lost in donating blood: Iron is mobilized from the body’s

iron stores Increased iron absorption from diet

Balance can be difficult to maintain in premenopausal females and regular blood donors since there is ongoing loss

Role of Oral Iron Replacement in the Routine Management of

Blood Donors (I.R.O.N. Protocol: “Iron Replacement or

Not”) NIH Protocol 06-CC-0166

Background 8-12% of all WB donor visits to DTM

end in deferral for low FS Hgb 3 - 4 year study at the NIH

Up to 2000 low hemoglobin donors Screening capillary fingerstick sample

by HemaCue device Up to 500 control donors

Goals of Study

Analyze the cause of low FS Hgb Quantitate the prevalence of Fe def Study the long-term effects of blood

donation on donors’ hemoglobin levels and iron stores

Evaluate the safety, practicality, and efficacy of distributing oral replacement iron to blood donors

Laboratory Testing

CBC Iron studies

Ferritin % transferrin saturation Serum iron Transferrin

Other labs (as indicated) Hemoglobin electrophoresis, etc.

Donor Health History Screening Questionnaire Focused medical history

screening to identify causes of low hemoglobin values and depleted or deficient iron stores

Identify concerns requiring referral to PCP

Identify need for additional laboratory testing

Iron Stores Definitions

Women: Ferritin normal range = 9-120 mcg/L Fe deficient: ferritin < 9 mcg/L Fe depleted: ferritin = 9-19 mcg/L Fe replete: ferritin ≥ 20 mcg/L

Men: Ferritin normal range = 18-370 mcg/L Fe deficient: ferritin < 18 mcg/L Fe depleted: ferritin = 18-29 mcg/L Fe replete: ferritin ≥ 30 mcg/L

Role of Oral Iron Replacement in the Role of Oral Iron Replacement in the Routine Management of Blood DonorsRoutine Management of Blood Donors

(I.R.O.N. Protocol: “Iron Replacement or Not”) (I.R.O.N. Protocol: “Iron Replacement or Not”) NIH Protocol 06-CC-0166NIH Protocol 06-CC-0166

39-month period 39-month period 1355 “Low FS Hemoglobin” donors 1355 “Low FS Hemoglobin” donors

1180 (87%) females, mean FS Hgb 11.81180 (87%) females, mean FS Hgb 11.8 175 (13%) males, mean FS Hgb 11.9175 (13%) males, mean FS Hgb 11.9

410 “Control” donors410 “Control” donors 147 (36%) females, mean FS Hgb 13.7147 (36%) females, mean FS Hgb 13.7 263(64%) males, mean FS Hgb 14.9263(64%) males, mean FS Hgb 14.9

Low Hgb Group (n= 1355)

Control Group (n = 410) p value

FemalesNumber of donors 1180 (87%) 147 (36%) <0.0001

Age (range) 40 (17-82) 46 (23-69) <0.0001

MalesNumber of donors 175 (13%) 263 (64%) <0.0001

Age (range) 53 (22-85) 48 (18-80) 0.0005

Race

Caucasian 924 (68%) 339 (83%) <0.0001

African American 230 (17%) 21 (5%) <0.0001

Asian 81(6%) 33 (8%) 0.1370

Hispanic 52 (4%) 7 (2%) 0.0403

Other 68 (5%) 10 (2%) 0.0275

First Time Donors

Number of donors 383 (28%) 46 (11%) <0.0001

# Prior Donations

Females WB (range) 10.2 (1-103) 15.8 (1-103) 0.0065

Males WB (range) 26.7 (1-172) 25.4 (1-185) 0.7185

Hgb = hemoglobin. WB = whole blood.

Donor Demographics

ResultsResults

Low Hgb GroupLow Hgb Group Females:Females:

3030% iron depleted% iron depleted 2323% iron deficient% iron deficient

Males:Males: 88% iron depleted% iron depleted 5353% iron deficient% iron deficient

Control GroupControl Group Females:Females:

2929% iron depleted% iron depleted 1010% iron deficient% iron deficient

Males:Males: 1818% iron depleted% iron depleted 2121% iron deficient% iron deficient

Association of FS Hgb Levels Association of FS Hgb Levels with Iron with Iron Status and Venous and Venous

Hgb in Hgb in ♀♀

WOMEN (n=1218)

Fingerstick Hemoglobin Levels (g/dL)

< 11.5 11.5-11.9 12.0-12.4 > 12.5

Iron Status % (n) %Menopause (n=256)   (n=303) (n=516) (n=143)

Fe deficient40% (102)

4%24% (73)

4%14% (70)

1%10% (14)

3%

Fe depleted26% (66)

5%28% (86)

4%32% (166)

5%29% (42)

7%

Fe replete34% (88)

6%48% (144)

11%54% (280)

13%61% (87)

24%

Venous Hgb > 12.5 18% (47) 35% (106) 55% (283)80% (115)

Association of FS Hgb Levels Association of FS Hgb Levels with Iron with Iron Status and Venous and Venous

Hgb in Hgb in ♂♂

MEN(n=420)

Fingerstick Hemoglobin Levels (g/dL)

< 12.012.0-12.4

12.5-12.9

13.0-13.4 > 13.5

Iron Status % (n)

(n=74)  (n=89) (n=9) (n=19) (n=229)

Fe deficient 62% (46) 46% (41) 56% (5) 26% (5) 19% (44)

Fe depleted 5% (4) 10% (9) 22% (2) 26% (5) 18% (40)

Fe replete 33% (24) 44% (39) 22% (2) 48% (9) 63% (145)Venous Hgb

> 12.5 55% (41) 69% (61) 78% (7) 95% (18) 100%(229)

FeSO4 or FeGluc 325 mg #60 1 tablet daily x 60 days

68% compliance 1065/1342 (79%) given FeSO4

235/1065 (22%) developed 235/1065 (22%) developed intolerance and switched to intolerance and switched to FeGluconateFeGluconate

46/1065 (4%) intolerant to both 46/1065 (4%) intolerant to both FeSO4 and FeGluconateFeSO4 and FeGluconate

Compliance with Oral Iron Compliance with Oral Iron Therapy and Adverse EffectsTherapy and Adverse Effects

Compliance Compliance withwith Oral Iron Oral Iron Therapy and Adverse EffectsTherapy and Adverse Effects

277/1342 (21%) reported intolerance to FeSO4 and started on FeGluconate 23/277 (8%) intolerant to FeGluconate

Overall, only 69/1342 (5%) intolerant to both FeSO4 and FeGluconate

Most common complaint – GI discomfort

Effect of Iron Therapy in Low-Fingerstick Hgb Donors

Effect of Iron Therapy in Low-Fingerstick Hgb Donors

Effect of Iron Therapy in Low Fingerstick Hgb Donors without Iron Depletion/Deficiency

Effect of Iron Therapy in Low Fingerstick Hgb Donors without Iron Depletion/Deficiency

Ferritin Values on Initial and Subsequent Visits of Donors

in Control Group

A. Control Donors not on Iron Therapy

B. Control Donors Started on Iron therapy after 1st Visit

C. Control Donors Started on Iron Therapy after 2nd Visit

D. Control Donors Started on Iron Therapy after 3rd Visit

E. Control Donors Started on Iron Therapy after 4th Visit

Safety

No donors were found to have ferritin and transferrin saturation levels suggestive of hemochromatosis

No malignancies reported or detected

All donors with Fe deficiency anemia given letter and copy of lab results to take to PCP

Correlation of Low MCV, Hemoglobin Levels, and Iron Stores

Apheresis donors at our facility are routinely evaluated with a CBC prior to each donation

Recurrent low red cell mean corpuscular volume (MCV) values (< 80 fL) in the presence of an acceptable hemoglobin ( 12.5 g/dL) in a donor population could be due to: Iron deficiency Hemoglobinopathy, such as alpha or beta

chain variant trait

Results

In a 15-month period, 30 of 1333 apheresis donors (43% African American, 7% Asian) had repeatedly low MCV values (Table 1)

Iron deficiency was present in 60%: 40% had isolated iron deficiency 20% had iron deficiency plus

hemoglobinopathy

Results (cont’d)

Hemoglobinopathy without concomitant iron deficiency was found in the remaining 40%

Frequent coexistence of iron deficiency and hemoglobinopathy resulted in a need for further laboratory evaluation, both before and after iron repletion, to confirm the diagnosis

Table 1. Low MCV Values in Apheresis Blood Donors

Causes Number (n=30)

Percentage

Iron deficiency 12 40

Hemoglobinopathy 12 40

---Alpha thal trait 8

---Hgb S trait and alpha thal trait 2

---Hgb G trait and alpha thal trait 1

---Hgb Lepore trait 1

Iron Deficiency and Hemoglobinopathy 6 20

---Alpha thal trait and iron deficiency 5

---Hgb C trait and iron deficiency 1

Conclusions - Low MCV Study

The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy in a healthy blood donor population

Low MCV values should be further investigated in the donor setting to determine if iron replacement therapy is indicated

Recommendations to FDA

Female donors Lower FS Hgb threshold to 12.0 g/dL

Male donors Raise FS Hgb threshold to 13.0 g/dL

Diplomatic Recommendations

Administer a 2-month supply of oral iron tablets to all donors with Hgb < 12.5 g/dL Males with previous blood donations:

Refer to PCP if hgb does not respond in 60 days

Males - 1st time donors: Refer to PCP

Males with Hgb < 12g/dL and Females with Hgb < 10g/dL

Refer to PCP

Evidenced-Based Recommendations

Routinely administer a 2-month supply of oral iron tablets, sufficient to replace iron lost in 1 unit of whole blood, to all whole blood donors Verify non-HH status by single ferritin

level

Acknowledgements

Sarah J. Arceo, RN Yu Ying Yau, RN Julie A. Hopkins, RN Susan F. Leitman, MD

Harvey G. Klein, MD

NIH Blood Donors