A Comparison of Serum Hepcidin and GDF15 Expression in Cases of Iron Depletion Due to Blood Loss.

Abstract 4043

Poster Board III-978

Iron depletion affects billions worldwide, and anemia develops when iron stores become insufficient to maintain normal erythropoiesis. Hepcidin is a negative regulator of iron absorption in the body. Low serum hepcidin levels provide a physiological response to iron demand in patients with iron deficiency. Based on a recent discovery of elevated growth differentiation factor 15 (GDF15) as a pathological suppressor of hepcidin in cases of thalassemia (Tanno et al. 2007), it was hypothesized that GDF15 may be elevated under physiological circumstances such as iron deficiency, but this area of research remains controversial. Here GDF15 and hepcidin levels were measured in the peripheral blood of subjects with iron-depleted erythropoiesis, and monitored in patients receiving iron replacement therapy. Initially, clinical studies were performed to measure GDF15 in the serum of iron-depleted blood donors (n = 10) and healthy volunteers (n = 10). Iron depletion was defined for this study as serum ferritin level (<10 ng/ml) and transferrin saturation (<15%). When compared to the control group, hemoglobin and RBC counts were also significantly reduced (p< 0.01) among the iron-depleted group. Serum hepcidin levels were also significantly reduced in the iron-depleted group (<5 ng/ml) compared to healthy volunteers (46 ± 41 ng/ml, p < 0.01). However, the GDF15 levels were not elevated in the iron-depleted group. Instead, iron-depletion was associated with a slight decrease in serum GDF15 (304 ± 90 pg/ml) compared to that in the control group (386 ± 104 pg/ml, p = 0.084). In three additional patients with iron depletion due to menstrual blood loss, serum GDF15 and hepcidin levels were monitored during oral iron replacement. In association with normalization of the ferritin and transferrin saturation, hepcidin levels increased in each patient, but GDF15 levels remained stable (202 ± 15 pg/ml versus 215 ± 23 pg/ml). In summary, iron depletion due to blood loss was not associated with increased GDF15, and there was no obvious correlation between GDF15 and hepcidin expression at the time of depletion or during iron replacement therapy. The data support the hypothesis that GDF15 elevation contributes to the pathological suppression of hepcidin and iron overload in cases of ineffective erythropoiesis rather than the physiological suppression of hepcidin in cases of iron depletion.