Prevention of Iron Deficiency in Surgical Patient


Iron deficiency is a leading cause of anemia. In adults, the condition derives almost exclusively from blood loss. Body iron stores for women normally vary between one and two grams while those of men average three to four grams. The liver is the source of most storage iron. Depletion of iron stores precedes failure to produce iron-containing proteins, most importantly hemoglobin. The two important stages of iron deficiency, then, are (a) depletion of iron stores without anemia, and (b) depletion of iron stores with anemia. Surigal patients in the latter category often require transfusion in the perioperative period. Less well appreciated is the fact that the patients in the former category frequently also require transfusion, as they lack the capacity to replenish hemoglobin lost during surgery. With adequate iron repletion prior to surgery, transfusion of these patients often can be circumvented.


Treatment of iron deficiency cannot be comfortably undertaken until the cause of the iron deficit is discovered. Blood loss into the gastrointestinal tract is by far the most common cause of iron deficiency <|[1]|>. Physicians should be aware of a couple of other possibilities, however.


Impaired iron absorption from the gastrointestinal tract rarely causes of iron deficiency. One etiology of increasing importance, however, is a high gastric pH. A high gastric pH reduces the solubility of inorganic iron, impeding its absorption. Surgical interventions, such as vagotomy or hemigastrectomy for peptic ulcer disease, formerly were the major causes of impaired gastric acidification. Iron deficiency developed as a secondary event. Today, the histamine H 2 blockers used to treat peptic ulcer disease and acid reflux are the most common causes of defective iron absorption <|[2]|>. Although these medications infrequently produce iron deficiency, their widespread use means that most physicians will encounter the problem at some time. The possible contribution of the acid pump inhibitors to iron deficiency has not been established unequivocally <|[3]|>.

Peptic ulcer disease can itself produce iron deficiency due to bleeding into the gastrointestinal tract (see below). The use of agents that block gastric acidification and iron absorption by people whose iron stores are low or absent is an excellent formula for producing iron deficiency anemia. Patients with peptic ulcer disease who come to surgery should be carefully scrutinized for evidence of iron deficiency.

Defects of the small intestine, including Crohns disease and Celiac disease (nontropical sprue), can also impair iron absorption. Unlike Crohns disease, celiac disease often disrupts iron absorption while manifesting only subtle clinical signs <|[4]|>. Some patients with mild celiac disease experience minor symptoms such as bloating after eating a meal rich in gluten, such as bran cereal. Nonetheless, the condition sometimes substantially impairs iron absorption <|[5]|>. Iron deficiency anemia occurs often when a concurrent predisposing condition exists, such as chronic use of aspirin or non-steroidal anti-inflammatory agents.
Some patients with deranged iron absorption lack gross or even histologic changes in the structure of the bowel mucosa.
A gluten-free diet improves bowel function in many such patients, with secondary correction of the anemia.


The gastrointestinal tract is both the site of iron uptake and the most common location of blood loss. This organ is unrivaled as a potential setting for occult bleeding. In adults, the chief specter is a gastrointestinal malignancy. In men with iron deficiency anemia, the gastrointestinal tract should be evaluated for possible malignancy. Peptic ulcer disease, hiatal hernia, or other benign lesions are the most common findings. However, a malignancy must be excluded.

The problem is complicated in women, where menstruation is a physiological source of blood loss. Iron deficiency anemia occurs in about 2% of premenopausal women due solely to menstruation. Iron stores are depleted in the absence of anemia in about 10% of premenopausal women. The fundamental dilemma is whether to pursue the issue of gastrointestinal blood loss (with malignancy as the key target), when a good explanation exists for the iron deficiency.

No clear-cut answer exists to this quandary, although one study suggests that a significant number of women in this category have lesions in the gastrointestinal tract <|[6]|>. Each situation must be considered carefully on its own merit. For example, in a 36 year-old mother of three children with a history of menorrhagia, gynecological and obstetrical blood loss alone are sufficient to explain iron deficiency anemia. Although gastrointestinal bleeding from a carcinoma could also contribute to the anemia, the chance of this is extremely small. Should stool guaiac cards over several days prove negative, iron replacement without further work-up is reasonable. In contrast, a 60 year-old post-menopausal woman with new onset iron deficiency should be evaluated for gastrointestinal sources of iron loss since physiological blood loss at this age does not occur.


Laboratory evaluation is essential to the diagnosis of iron deficiency <|[Table I]|>. Physical signs, such as koilonychia, glossitis, and angular stomatitis are rare. These abnormalities manifest themselves most commonly in severe, long-standing iron deficiency which rarely occurs in industrialized nations. The most common symptom is easy fatigue caused by the anemia that accompanies advanced iron deficiency <|[7]|>. Even fatigue is often absence in patients with moderately severe iron deficiency anemia. The anemia develops slowly, and many people subconsciously adapt their activity and expectations to fit their diminished stamina. Classical manifestations, such as geophagia, are rare.

The three key laboratory tests in the analysis of iron deficiency are the plasma ferritin, plasma iron, and the total iron binding capacity (TIBC). In uncomplicated cases, a low plasma ferritin is sufficient to make the diagnosis of iron deficiency. The plasma iron and TIBC are used together to determine the transferrin saturation (the ratio of the plasma iron to the TIBC.) With uncomplicated iron deficiency, the transferrin saturation is low.

Often, however, the diagnosis of iron deficiency must be made in the setting of potentially confounding conditions <|[8]|>. The most common situation that presents a diagnostic dilemma is chronic inflammation. Chronic rheumatoid arthritis, for instance, frequently produces a moderately severe normochromic, normocytic anemia. In addition, this process raises the plasma ferritin level, which can mask coexistent iron deficiency. Chronic inflammation depresses both the plasma iron and the TIBC, complicating the interpretation of these parameters with respect to iron deficiency.

A common scenario is a patient with rheumatoid arthritis who takes non-steroidal anti-inflammatory agents for pain control <|[9]|>. These agents increase the likelihood of gastrointestinal bleeding due to irritation of the stomach lining and inhibition of platelet function. A review of the full panel of laboratory data, including a complete blood count (CBC), evaluation of the peripheral smear, as well as assay of plasma ferritin and transferrin saturation can sometimes provide a sense of whether iron deficiency, in addition to the chronic inflammation, plays a role in the anemia. If this approach fails, a definitive diagnosis of iron deficiency can be made only by bone marrow biopsy, with staining for iron.

Substantial iron deficiency produces a hypochromic, microcytic anemia. The most important alternate condition to rule out is thalassemia trait, also called thalassemia minor. A little-used datum that accompanies every electronic counter blood analysis called the RDW (red cell distribution width) can be extremely helpful in distinguishing between iron deficiency anemia and thalassemia trait <|[10]|>. The RDW is normal in thalassemia trait (reflecting the uniformly small size of the red cells), but often is elevated in iron deficiency anemia, where variation in red cell size is common.

Review of the blood smear is also helpful in distinguishing between these two conditions. Target cells are common in the smear of patients with thalassemia trait, but are infrequent with iron deficiency. A further consideration in the use of the RDW and peripheral smear is that they add nothing to the cost of the work-up. If the issue is still in doubt, a hemoglobin electrophoresis will usually settle the question. The hemoglobin A2 (and often the hemoglobin F) level is elevated in patients with thalassemia trait.



Although physicians commonly recommend ferrous sulfate to treat iron deficiency, frequent problems with the drug including gastrointestinal discomfort, bloating and other distress, make it unacceptable to many patients. Ferrous gluconate, which is roughly equivalent in cost, produces fewer problems and is preferable as the initial treatment of iron deficiency.

Each 300 mg ferrous gluconate tablet contains 50 mg of elemental iron. Ascorbic acid substantially enhances iron absorption <|[11]|>. Preparations that combine iron salts and ascorbic acid are significantly more expensive than separate tablets for each, however. A reasonable approach to oral iron supplementation is one ferrous gluconate tablet and one 250 mg ascorbic acid tablet twice a day.

Iron is best absorbed when taken between meals because some food components (for example, phytates in wheat products) complex with iron in the gastrointestinal tract and prevent its uptake <|[12]|>. Abdominal distress is less common when iron supplements are taken with meals, however. Therefore, the pattern of replacement must be balanced between patient comfort and drug efficacy. Non-compliance with oral iron is one of the most common causes of therapeutic failure with oral iron supplementation. Even with faithful use of oral iron, adequate replacement of body stores in patients with moderate iron deficiency anemia requires several months. With ongoing blood loss, replacing stores using oral iron supplements becomes an Olympian task.

Polysaccharide-iron complex (Niferex), a replacement form of iron that differs from the iron salts, is now available. The polar oxygen groups in the polysaccharide form coordination complexes with the iron atoms. The well-hydrated microspheres of polysaccharide iron remain in solution over a wide pH range, which possibly is an advantage for absorption. This has not been proven, however. Many patients tolerate this form of iron better than iron salts, even though the 150 mg of elemental iron per tablet is substantially greater than that provided by iron salts (50 to 70 mg per tablet).


Parenteral iron is available in the US only as iron-dextran (INFeD). A number of iron saccharates are available for clinical use in other parts of the world. These medications are indicated when 1) oral iron is poorly tolerated, 2) rapid replacement of iron stores is needed, or 3) gastrointestinal iron absorption is compromised. Intramuscular injection or intravenous infusion are the two potential routes of parenteral iron administration. Intramuscular injection of iron-dextran can be painful, and leakage into the subcutaneous tissue produces long-standing skin discoloration.

A Z-track injection into the muscle minimizes the chance of subcutaneous leak. Suboptimal muscle mass in patients with concomitant nutritional deficiency frequently further complicates this mode of replacement. Intravenous infusion of iron-dextran circumvents these problems altogether. With either route of administration, the physician should observe the patient for
30 minutes after the 10 mg test dose to rule out an anaphylactic reaction to the medication (such reactions are infrequent).

Intravenous boluses of iron dextran or iron saccharates are well tolerated. Only a limited quantity of iron can be administered by this route (100 mg of elemental iron in the case of iron dextran; 125 mg of elemental iron in the case of iron saccharates). Some patients have iron deficits sufficiently profound as to require a larger quantity of iron to correct an anemia of iron deficiency.

In these instances, iron dextran can be administered as a total dose replacement, replenishing all or most of the iron deficit at a single stroke <|[13]|>. After the initial test dose, up to three grams of iron dextran are diluted into 500 ml of normal saline for the infusion. A rate-controlled pump regulates the infusion of the medication over the four to five hours required for administration. The physician need not be at the immediate scene of the infusion, but should be readily available. <|[Table II]|> outlines the procedure for total dose infusion parenteral iron replacement.

This bulk infusion of iron dextran obviates the need for repeated preoperative clinic visits by patients to receive parenteral iron. The one hundred mg limit for iron dextran bolus infusion means that a person with a two gram deficit would need twenty clinic visits to correct the iron deficiency. The time needed to carry out such a treatment plan rarely is available, even with elective surgery. Also, the cost of this approach is much greater owing to the number of outpatient visits required. The total dose infusion approach for iron dextran is not approved by the US Food and Drug Administration. Nonetheless, the technique is used extensively in the US and other countries to replenish iron stores of patients with substantial iron deficiency. Large dose infusions of the iron saccharides generally are not used. Nonetheless, these agents are superior to oral iron supplementation for correction of iron deficiency <|[14]|>.

About 10% to 15% of patients experience transient mild to moderate arthralgias or myalgias the day after intramuscular or intravenous administration of iron-dextran. Acetaminophen usually effectively relieves the discomfort. Iron-dextran can be a particular problem for patients with rheumatoid arthritis who frequently have painful flairs of their disease after receiving the drug. Administration of 60 mg of intravenous methylprednisolone prior to the iron dextran usually abrogates this problem, however.

In uncomplicated cases of iron deficiency, intravenous iron replacement improves symptoms in a few days. Peak reticulocytosis occurs after about 10 days, and complete correction of even severe anemia (e.g., Hb = 5 g/dl) takes only 3 to 4 weeks <|[15]|>. The hematocrit rises sufficiently in a week or two to provide symptomatic relief for most patients. Most importantly, a preoperative patient with a hemoglobin of 7 g/dl can achieve a value of 11 to 12 g/dl in this time frame. An improvement of this magnitude substantially lowers the probability that the patient will require transfusion.


Oral iron replacement to correct iron deficiency anemia is a time consuming process. A person of 70 kg weight with a hemoglobin of 8.5 g/dl would have a body iron deficit of about 1700 gm. Daily iron absorption is about 2 mg. This value can increase to as much as 10 mg with iron deficiency. An oral iron replacement regimen would require nearly 6 months to completely correct the iron deficit in this patient. Such a time frame is unacceptable for most patients who require surgery.

The type of surgery and its estimated blood loss also enters the equation of the timing of iron replacement therapy. Whole blood contains about one-half gram of iron per ml. Loss of 500 ml of blood during a total hip replacement for instance entails the loss of 250 mg of iron. If the patients iron stores were depleted going into the procedure, the blood loss could not be corrected by endogenous red cell production. Iron replacement before the procedure could abrogate the need for transfusion later in the course.

Patients slated for elective surgery should be evaluated for iron deficiency as far in advance as possible. Two to three weeks provides a minimum window in which to correct even severe iron deficiency anemia. Parenteral iron replacement should be used in this setting since oral iron replacement will not have time to work.



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