Iron Status in Blood Donors

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 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

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 • 1355 “Low FS Hemoglobin” donors • 1180 (87%) females, mean FS Hgb 11.8 • 175 (13%) males, mean FS Hgb 11.9 • 410 “Control” donors • 147 (36%) females, mean FS Hgb 13.7 • 263(64%) males, mean FS Hgb 14.9

10. Donor Demographics

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

12. Association of FS Hgb Levels with Iron Status and Venous Hgb in ♀

13. Association of FS Hgb Levels with Iron Status and Venous Hgb in ♂

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

15. Compliance with Oral Iron Therapy 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

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

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

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

19. 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 • Control Donors not on Iron Therapy • Control Donors Started on Iron therapy after 1st Visit • Control Donors Started on Iron Therapy after 2nd Visit • Control Donors Started on Iron Therapy after 3rd Visit • Control Donors Started on Iron Therapy after 4th 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

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 - 1st 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