How we diagnose and treat iron deficiency anemia

Abstract

It is estimated that one‐third of the world's population is anemic, the majority being due to iron deficiency (ID). In adults, ID is associated with fatigue in the absence of anemia, restless legs syndrome, pica and, in neonates, delayed growth and development. In adolescents, ID is associated with decrements in learning and behavioral abnormalities. In the absence of a clear cause, search for a source of bleeding is indicated. No single test is diagnostic of ID unless the serum ferritin is low or the percent transferrin saturation is low with an elevated total iron binding capacity. Oral iron is considered front line therapy except for conditions such as gastric bypass, heavy uterine bleeding, inflammatory bowel disease, and hereditary hemorrhagic telangiectasia. Oral iron has many unpleasant side effects, resulting in low patient adherence. For patients intolerant of, or unresponsive to, oral iron, intravenous (IV) administration is the preferred route. While early formulations were associated with a high incidence of serious adverse events (SAEs), newer formulations are much safer with SAEs occurring very infrequently. Full replacement doses can be administered in a matter of minutes to a few hours. Nevertheless, there remains a reluctance to use IV iron due to a misunderstanding of the safety of the available formulations. IV iron is safe and effective in all clinical circumstances including pregnancy. The preponderance of published evidence suggests IV iron therapy is underutilized and we believe that IV iron should be moved forward in the treatment of ID and iron deficiency anemia (IDA). Am. J. Hematol. 91:31–38, 2016. © 2015 Wiley Periodicals, Inc.

Modern iron replacement therapy: clinical and pathophysiological insights

“…This leads to the presence of toxic labile-free iron, once the binding capability of transferrin is saturated. As a general rule, the more stable is the complex, the less will be the frequency of infusion reactions, which are usually mild, consisting of rash, palpitations, dizziness, myalgias, and chest discomfort in variable combination but without hypotension or respiratory symptoms [49]. Such minor infusion reactions occur roughly in 1:200 administrations [102], and resolve quickly by simply stopping the infusion without the need of any other treatment.…”

“…like during acute inflammation) to be substantially suppressed it needs to be reduced by a brush-border ferrireductase (duodenal cytochrome b or DCYTB), allowing the resulting divalent iron to enter the luminal surface of enterocytes through a specialized transporter (Divalent Metal Transporter 1, or DMT1). By contrast, the absorption of heme-iron is less well understood [48], and attempts to produce heme-iron polypeptides has resulted in greater costs and insufficient clinical evaluation [49]. Thus, for the moment divalent iron salts appear the most appropriate form of oral iron replacement therapy, the most used being ferrous gluconate, ferrous fumarate, and ferrous sulfate (FS) ( Table 2).…”

“…Such minor infusion reactions occur roughly in 1:200 administrations [102], and resolve quickly by simply stopping the infusion without the need of any other treatment. Of note, there is increasing consensus on avoiding anti-histaminic drugs in such conditions, with particular reference to diphenhydramine, as it could determine hypotension and other unwanted side effects, leading to paradoxical aggravation rather than amelioration of the clinical picture [49,103]. More serious "anaphylactoid" reactions, including hemodynamic and respiratory changes, can also occur with virtually all IV iron preparations, including the newer ones (see below), but appear exceedingly rare (see below).…”

“…Optimal response to oral iron is generally defined as an hemoglobin increase of 2 g/dl after 3 weeks. However, the final goal of the treatment has to be not only the normalization of hemoglobin, but also repletion of iron stores, with an ideal target of ferritin > 100 μg/l [49,51]. This often requires a prolonged treatment for at least 3 months [50], if not more.…”

Is low‐molecular weight iron dextran really the most risky iron?—Unconvincing data from an unconvincing study

“…This knowledge has led to a protocol that treats iron reactions for the infusion reactions they are instead wrongly treated as allergic reactions (Table II) [9,11,12]. This includes treating mild reactions (flushing, itching) with holding the infusion for 15 min and if the patient improves resuming the infusion at a reduced rate diphenhydramine is to be avoided.…”