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638 Part VI: The Erythrocyte Chapter 43: Iron Deficiency and Overload 639

packaging of medications. In the United States, there were nearly dosing, the amount of iron per infusion, and infusion rates differ among
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30,000 reported incidents in 2008. The earliest manifestation of iron the preparations, these are not based on comparative studies. Currently
poisoning is vomiting, usually within 1 hour of the ingestion. There available data indicate that the preparations do not significantly differ
may be hematemesis or melena. Restlessness, hypotension, tachypnea, in safety or efficacy. Premedication to prevent allergic responses was
and cyanosis may develop soon thereafter, and may be followed within commonly used with the older preparations but it is neither needed nor
a few hours by coma and death but fatal outcomes are now extremely known to be effective with the newer formulations, and may introduce
rare. Usually, medical aid is sought early and, with proper treatment, side effects of its own.
most iron-poisoned children survive. The initial treatment is prompt
evacuation of the stomach. In the home, this may be induced by dig- COURSE AND PROGNOSIS
ital stimulation of the pharyngeal gag reflex. If the patient arrives in Course
the emergency room within minutes of ingestion, gastric intubation If therapy is adequate, the correction of iron-deficiency anemia is usu-
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and lavage should be performed promptly. Whole-bowel irrigation is ally gratifying. Symptoms such as headache, fatigue, pica, paresthesia,
currently recommended to for all heavy metal intoxications. Supportive and burning sensation of the oropharyngeal mucosa may abate within a
measures should be used as needed for shock or for metabolic acidosis few days. In the blood, the reticulocyte count begins to increase after a
should these develop. IV desferrioxamine is the agent of choice for specific few days, usually reaches a maximum at approximately 7 to 12 days, and
therapy of hyperferremia, at a maximum rate of 15 mg/kg per hour for thereafter decreases. When anemia is mild, little or no reticulocytosis
1 hour, then lowered to 125 mg/hour. Improvement often appears several may be observed. Little change in hemoglobin concentration or hema-
hours to a few days after onset of iron poisoning. Children who survive tocrit value is to be expected for the first 2 weeks, but then the anemia
for 3 or 4 days usually recover without sequelae. However, gastric stric- is corrected rapidly. The hemoglobin concentration in the blood may
tures and fibrosis or intestinal stenosis may occur as late complications.
be halfway back to normal after 4 to 5 weeks of therapy. By the end of 2
months of therapy, and often much sooner, the hemoglobin concentra-
Parenteral Iron Therapy tion should have reached a normal level.
Indications As parenteral iron preparations have become safer and eas- When iron-deficiency anemia does not resolve with oral iron treat-
ier to administer, the use of parenteral iron is increasing. Established ment, careful inquiry into the nature, duration, and regularity of iron
indications for the use of parenteral rather than oral iron include mal- therapy may reveal a reason for the failure of therapy and permit a grati-
absorption, either because of systemic inflammation or gastrointestinal fying response to be elicited with adequate therapy. Other questions that
pathology, intolerance to iron taken orally, iron need in excess of an should be asked in evaluation of such a case are these: (1) Has bleeding
amount that can be absorbed in the intestine, and noncompliance. Par- been controlled? (2) Has the patient been on iron therapy long enough
enteral iron administration has an erythropoietin-sparing effect in ane- to show a response? (3) Has the dose of iron been adequate? (4) Are
mic patients on long-term hemodialysis for chronic renal disease. 35,199,200 there other factors—inflammatory disease, neoplastic disease, hepatic
Because of systemic inflammation and possibly other factors, these or renal disease, prior gastrointestinal surgery, concomitant deficiencies
patients do not appear to respond adequately to oral iron therapy. (vitamin B , folic acid, thyroid)—that might retard response? Prom-
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Calculating Dosage The amount of iron that needs to be given inent among these are H. pylori infection, autoimmune gastritis, and
is readily estimated by noting that 1 mL of red cells contains approxi- celiac disease. (5) Is the diagnosis of iron deficiency correct?
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mately 1 mg of iron. However, various formulas have been used for esti- Intravenous iron should be effective in patients with established iron
mating total dose required for treatment. Because total blood volume deficiency who fail to respond to oral iron after several weeks. Contin-
is approximately 65 mL/kg and the iron content of hemoglobin is 0.34 ued loss of blood or, rarely, the genetic disorder iron-refractory iron-defi-
percent by weight, the simplest formula for estimating the total dose ciency anemia, may account for incomplete response to IV iron.
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required for correction of anemia only is as follows:
Prognosis
The dose of iron (mg) = Whole-blood hemoglobin deficit (g/dL)
× Body weight (lb) When the cause of the iron deficiency is a benign disorder, the prognosis
is excellent, provided bleeding is controlled or can be compensated for
Assuming normal mean hemoglobin concentration of 16 g/dL, a by continual iron therapy. If there is a benign cause of recurrent bleeding
male weighing 170 pounds, whose hemoglobin concentration is 7 g/dL, that is corrected, such as hiatal hernia, menorrhagia, or hereditary hem-
would require 170 × (16 − 7) = 1530 mg iron to correct this anemia. To orrhagic telangiectasia, oral iron therapy may be continued indefinitely;
this should be added a sufficient quantity of iron to replete iron stores, if the bleeding is especially brisk, supplementation with parenterally
approximately 1000 mg for men and approximately 600 mg for women. administered iron or, rarely, with transfusion may be needed. Contin-
Thus a 170-pound male with a hemoglobin concentration of 7 g/dL uous iron administration may also be required in patients with iron
should receive 2530 mg iron. deficiency secondary to intravascular hemolysis with hemoglobinuria.
Parenteral Iron Preparations Because iron salts are highly toxic
when given parenterally, all iron preparations consist of colloidal
(nanoparticulate) complex of iron with carbohydrates. To make the IRON STORAGE DISEASE
iron bioavailable for erythropoiesis and other biologic processes, the
iron complexes must be ingested by macrophages and digested so that DEFINITION AND HISTORY
the administered iron can be gradually delivered to plasma transferrin. The terms iron storage disease and hemochromatosis are used to desig-
Currently available preparations include iron sucrose, low-molecu- nate an increase of tissue iron resulting in a disease state; hemosiderosis
lar-weight iron dextran, ferric gluconate, ferumoxytol, ferric carboxy- denotes an increase of tissue iron stores with or without tissue damage.
maltose, and iron isomaltoside. High-molecular-weight dextran was Classically hemochromatosis has been characterized by bronzing of the
associated with anaphylactoid adverse events compared to the other skin, cirrhosis, and diabetes, and was once called bronzed diabetes. Since
preparations and should therefore be avoided. The remaining prepara- the 1970s, usage of the term hemochromatosis has expanded well beyond
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tions are safe and serious adverse events are extremely rare. Although its original meaning. This diagnosis is now commonly applied to per-
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the recommended methods of administration, including the use of test sons who have increased body iron as suggested by increased serum

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