Causes of Iron Deficiency

Blood Loss

A common cause of iron deficiency anemia is blood loss.9 The amount of iron lost in each milliliter of blood depends on the hematocrit or red blood cell content of the blood. Each milliliter of healthy red blood cells contains 1 mg elemental iron. So, for example, a blood loss of 100 mL at a hematocrit of 40% will result in a loss of ~40 mg iron.2 Following significant blood loss, the bone marrow is stimulated by erythropoietin to increase production of hemoglobin, which depletes iron stores.3,4 Once iron stores are depleted, a microcytic, hypochromic anemia results.3

Chronic gastrointestinal bleeding

Blood loss may be chronic. For men and postmenopausal women, bleeding in the GI tract is the most common cause of blood loss-related iron deficiency anemia.9 In patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, iron deficiency is generally caused by sustained and commonly unnoticed bleeding due to intestinal inflammation and permanent mucosal barrier disruption.10 In one study, of the 30% of IBD patients who were anemic, two-thirds were iron deficient.11

Apart from Crohn's disease and colitis, other common causes of occult GI bleeding include chronic NSAID use, colon cancer or polyps, gastric cancer, angiodysplasia, and chronic kidney disease (CKD).9

Heavy menstrual bleeding

But for premenopausal women the most common cause of iron deficiency anemia is heavy menstrual bleeding9(loosely defined as menses lasting >7 days or total blood loss of >80 mL per menses).13 In the 5% to 10% of menstruating women who experience iron deficiency anemia,9 the blood loss may exceed the absorptive capacity for iron and patients may require parenteral iron to replenish iron stores quickly.4

Hemodialysis-dependent chronic kidney disease

Iron deficiency is frequently found in CKD patients, in both dialysis patients and those not on dialysis. In dialysis patients, iron deficiency may be attributed to blood loss in the dialysis filter and dialysis lines, frequent phlebotomy, and bleeding through the access site.14

Malabsorption of dietary iron

Since iron absorption occurs primarily in the duodenum and proximal jejunum,10,15 malabsorption of dietary iron can occur in patients who have undergone gastric bypass, partial or full gastrectomy, or resection of the gut.15 It may also occur in patients with chronic diseases such as celiac disease or Whipple's disease that affect absorption of nutrients in the small bowel.9

Gastrectomy and gastric bypass

In patients who have undergone gastric bypass surgery, iron deficiency is common, reported in 20% to 47% of patients.16,17 This can occur because not only is the acidic environment of the stomach bypassed, but so are the absorptive surfaces of the duodenum and proximal jejunum, reducing the absorption of iron.15

Documented Iron Deficiency Coexisting with Cancer

The prevalence of iron deficiency in cancer patients may be as high as 50% to 60%.18,19 Iron deficiency, with or without anemia, in cancer patients may be due to GI blood loss (as in the case of colorectal cancer patients).18 However, several recent studies have demonstrated hepcidin upregulation in patients with leukemia, multiple myeloma, and other malignancies.20,21 In vitro data suggest that P53-mediated upregulation of hepcidin, which promotes sequestration of iron and reduced absorption of iron from the gut,22 may be a defense mechanism against cancer, depriving cancer cells of iron for growth.23 This upregulation of hepcidin may be responsible for the anemia seen in cancer patients. Hepcidin promotes sequestration of iron within storage sites, so serum ferritin levels may be elevated in cancer patients.22

Treatment with erythropoiesis-stimulating agents (ESAs) for cancer-related and chemotherapy-related anemia may also lead to a functional iron deficiency, in which the iron in storage sites cannot be released quickly enough for use in ESA-driven erythropoiesis.24 In fact, about 30% to 50% of cancer patients fail to achieve a meaningful response to ESA therapy;25 iron deficiency may be the response-limiting factor.26

Causes of Iron Deficiency- Insufficient dietary intake

References

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INFeD is indicated in the treatment of patients with documented iron deficiency in whom oral administration is unsatisfactory or impossible.

Important Safety Information

Anaphylactic-type reactions, including fatalities, have followed the parenteral administration of iron dextran injection. A test dose should be administered prior to the first therapeutic dose, followed by the full therapeutic dose if no signs or symptoms of anaphylactic-type reactions are seen. Resuscitation equipment and personnel trained in the detection and treatment of anaphylactic-type reactions must be readily available during all INFeD administrations. Patients should be observed for signs or symptoms of anaphylactic-type reactions during all INFeD administrations. Fatal reactions have followed the test dose and have also occurred in situations where the test dose was tolerated. Use INFeD only in patients in whom clinical and laboratory investigations have established an iron deficient state not amenable to oral iron therapy. Patients with a history of drug allergy or multiple drug allergies may be at increased risk of anaphylactic-type reactions. INFeD should be used with caution in individuals with histories of significant allergies and/or asthma, and is contraindicated in patients with hypersensitivity to the product and patients with all anemias not associated with iron deficiency. INFeD should be used with extreme care in patients with serious impairment of liver function, and should not be used during the acute phase of infectious kidney disease. Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of exogenous hemosiderosis, which is particularly apt to occur in patients with hemoglobinopathies and other refractory anemias.