1. Iron Status in Blood Donors Barbara J. Bryant, MD University of Texas Medical Branch Galveston, Texas and Department of Transfusion Medicine National Institutes of Health Bethesda, Maryland

2. Iron Deficiency in Blood Donors Iron deficiency in 1 st 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

3. 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

4. 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

5. 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

6. Laboratory Testing CBC Iron studies   Ferritin   % transferrin saturation   Serum iron   Transferrin Other labs (as indicated)   Hemoglobin electrophoresis, etc.

7. 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

8. 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

9. 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 39-month period 39-month period 1355 “Low FS Hemoglobin” donors 1355 “Low FS Hemoglobin” donors  1180 (87%) females, mean FS Hgb 11.8  175 (13%) males, mean FS Hgb 11.9 410 “Control” donors 410 “Control” donors  147 (36%) females, mean FS Hgb 13.7  263(64%) males, mean FS Hgb 14.9

10. Low Hgb Group (n= 1355) Control Group (n = 410)p value Females Number of donors 1180 (87%)147 (36%)<0.0001 Age (range) 40 (17-82)46 (23-69) <0.0001 Males Number 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 MalesWB (range) 26.7 (1-172)25.4 (1-185) 0.7185 Hgb = hemoglobin. WB = whole blood. Donor Demographics

11. Results Low Hgb Group Low Hgb Group  Females:  30% iron depleted  23% iron deficient  Males:  8% iron depleted  53% iron deficient Control Group Control Group  Females:  29% iron depleted  10% iron deficient  Males:  18% iron depleted  21% iron deficient

12. Association of FS Hgb Levels with Iron and Venous Hgb in ♀ Association of FS Hgb Levels with Iron Status and Venous Hgb in ♀ WOMEN (n=1218) Fingerstick Hemoglobin Levels (g/dL) < 11.511.5-11.912.0-12.4> 12.5 Iron Status % (n) %Menopause (n=256) (n=303)(n=516)(n=143) Fe deficient 40% (102) 4% 24% (73) 4% 14% (70) 1% 10% (14) 3% Fe depleted 26% (66) 5% 28% (86) 4% 32% (166) 5% 29% (42) 7% Fe replete 34% (88) 6% 48% (144) 11% 54% (280) 13% 61% (87) 24% Venous Hgb > 12.5 18% (47)35% (106)55% (283)80% (115)

13. Association of FS Hgb Levels with Iron and Venous Hgb in ♂ Association of FS Hgb Levels with Iron Status and Venous Hgb in ♂ MEN (n=420) Fingerstick Hemoglobin Levels (g/dL) < 12.012.0-12.4 12.5- 12.913.0-13.4> 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)

14. FeSO 4 or FeGluc 325 mg #60   1 tablet daily x 60 days 68% compliance 1065/1342 (79%) given FeSO 4  235/1065 (22%) developed intolerance and switched to FeGluconate  46/1065 (4%) intolerant to both FeSO4 and FeGluconate Compliance with Oral Iron Therapy and Adverse Effects

15. 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 FeSO 4 and FeGluconate Most common complaint – GI discomfort

16. Effect of Iron Therapy in Low-Fingerstick Hgb Donors

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

20. 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 1 st Visit C.Control Donors Started on Iron Therapy after 2 nd Visit D.Control Donors Started on Iron Therapy after 3 rd Visit E.Control Donors Started on Iron Therapy after 4 th Visit

21. 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

22. 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

23. 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

24. 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

25. Table 1. Low MCV Values in Apheresis Blood Donors CausesNumber (n=30) Percentage Iron deficiency1240 Hemoglobinopathy1240 ---Alpha thal trait8 ---Hgb S trait and alpha thal trait2 ---Hgb G trait and alpha thal trait1 ---Hgb Lepore trait1 Iron Deficiency and Hemoglobinopathy620 ---Alpha thal trait and iron deficiency5 ---Hgb C trait and iron deficiency1

26. 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

27. 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

28. 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 - 1 st time donors: Refer to PCP   Males with Hgb < 12g/dL and Females with Hgb < 10g/dL Refer to PCP

29. 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

30. Acknowledgements Sarah J. Arceo, RN Yu Ying Yau, RN Julie A. Hopkins, RN Susan F. Leitman, MD Harvey G. Klein, MD NIH Blood Donors