Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia.

Bregman DB, Morris D, Koch TA, He A, Goodnough LT
Am J Hematol 2013;88:97-101.
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Review by : M. Muñoz
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Forty-four random patients with iron deficiency anemia (IDA; serum ferritin <100 µg/L, or serum ferritin <300 µg/L and TSAT <30%) underwent a 14-day trial course of oral iron therapy (OIT; 325 mg iron sulphate, t.i.d.), and a baseline hepcidin >20 µg/L was found to predict non-responsiveness to OIT (Hb increase <1 g/dL). The ability of baseline hepcidin to detect non-responders to OIT was confirmed in a larger analysis of 240 IDA patients (90 responders, 150 non-responders), and was shown to be superior to TSAT >15% or ferritin >30 µg/L for this purpose (positive predictive values 82, 59 and 56 percent, respectively). The authors concluded that “screening hepcidin levels can predict patients who are non-responders, thus making oral iron therapy both undesirable and unnecessary”.

Nevertheless, this statement deserves some comments. First, the criteria for IDA diagnosis are quite “conservative”. However, mean ferritin and TSAT values in the study population were close to those “traditionally” accepted for IDA, especially in the groups of responders. Second, as hepcidin assessment is not available in most laboratories, it would have been interesting to ascertain whether other parameters more commonly used for IDA (ACD + IDA) diagnosis (e.g., hypochromic red cells, reticulocyte Hb, soluble transferrin receptor, inflammatory markers, etc.) could be of help in predicting the non-responsiveness to oral iron.

Forty-five out of 150 non-responders who had hepdicin levels assessed at the end of oral iron course (mean values 30-40 µg/L) were randomized to receive ferric carboxymaltose (FCM; 2 x 750 mg, IV; n = 22) or continue with oral iron for an additional 14 days (OIT; n = 23). Hb levels and iron status were assessed up to 35 days. From baseline to day 35, hepcidin levels increased by 120 µg/L in FCM subjects (reflecting increased iron stores) and remained unchanged in patients receiving OIT. Similarly, compared to OIT, there were more FCM subjects with a hemoglobin increment >1 g/dL (65.3% vs. 20.8%) or >2 g/dL (37.5% vs. 5.2%) (reflecting increased iron availability for erythropoiesis in FCM subjects). The authors conclude that “non-responsiveness to OIT does not rule out IDA, since IV FCM therapy produced Hb responses in two-thirds of patients who had no response to a trial of OIT”. This is an important message for physicians managing IDA patients, such as general practitioners, gynecologists and gastroenterologists, who should consider early shifting to IV iron when OIT is not efficacious.

– Manuel Muñoz