ID was defined as a serum ferritin level less than 10 ng/mL and a transferrin saturation less than 15%. Transferrin saturation, ferritin, hepcidin, and GDF15 levels were determined using venous blood from 10 blood donors with ID, as well as 10 healthy volunteers who had no evidence of ID (control group). Clinical and laboratory data in these subjects are shown in Tables S1A and S1B
(available as supporting information in the online version of this paper). Serum iron, ferritin, and transferrin saturation were significantly lower (p < 0.05) in the ID group compared to controls. The hematologic variables were consistent with irondeficient erythropoiesis with reductions in plasma hemoglobin, red blood cell counts, and mean corpuscular volumes. Hepcidin levels were also significantly reduced to levels at or below the limit of detection (<5 ng/mL) in the ID samples compared to the control group (46 ± 41 ng/mL, p < 0.01), and transferrin levels were elevated. The reduced hepcidin levels are consistent with previously reported results using the same method of hepcidin measurement.3
Based on the consistently low level of serum hepcidin detected in the donor population studied here, it is predicted that hepcidin levels may eventually be useful for the identification of blood donor subpopulations who require iron supplementation.
In addition to standard iron variables and hepcidin measurements, GDF15 levels were assayed on frozen serum samples. As shown in , serum GDF15 levels were not increased in the ID group. Mean GDF15 levels were 386 ± 104 pg/mL in the control group and 307 ± 90 pg/mL in the ID group. The slight reduction in mean GDF15 concentration in the ID group did not reach significance (p = 0.085). GDF15 studies were also performed after iron supplementation in four individuals (one blood donor and three subjects with ID due to menstrual blood loss). A summary of the clinical data on those four subjects is shown in Table S1C
. For comparison purposes, hepcidin and GDF15 levels were measured after the serum ferritin and transferrin saturation reached levels of more than 10 ng/mL and more than 15%, respectively. As shown in , iron concentration, transferrin saturation, and serum hepcidin levels increased with iron supplements in each individual. However, serum GDF15 levels remained static in the presupplement (247 ± 101 pg/mL) and postsupplement (266 ± 103 pg/mL) samples (p = 0.81).
Fig. 1 Transferrin saturation, ferritin, hepcidin, and GDF15 levels in serum from iron-deficient subjects. (A) Transferrin saturation (%Sat.), (B) ferritin, (C) hepcidin, and (D) GDF15 levels in serum from healthy volunteers (HV) and iron-deficient blood donors (more ...)
Fig. 2 Iron, transferrin saturation, hepcidin, and GDF15 levels in serum from iron-deficient subjects before and after oral iron supplements. (A) Iron, (B) transferrin saturation (%Sat.), (C) hepcidin, and (D) GDF15 levels in serum before iron treatment (Pre) (more ...)