Management Considerations
There are certain conditions that are associated with iron deficiency and certain considerations should be made when managing the iron deficiency. One reason for this is that some of these disorders are associated with inflammation, which results in increased hepcidin and therefore reduced iron (dietary and/or from oral iron supplements) absorption and mobilization, resulting in functional iron deficiency with or without absolute iron deficiency. Therefore, parenteral iron is considered as first line in the treatment of functional iron deficiency, including for patients with congestive hearth failure, inflammatory bowel disease, preoperative anemia, chronic kidney disease, or pregnancy.
Congestive Heart Failure
Anemia and functional iron deficiency are common in heart failure due to multiple factors, including increased levels of inflammatory cytokines, renal insufficiency, and poor nutrition. Moreover, anemia is associated with more advanced heart failure, likely secondary to decreased oxygen supply and myocardial injury resulting in ventricular remodelling, and mortality.
It is essential that a complete blood count, ferritin levels, and iron profile is assessed in these patients, and in case of iron deficiency, with or without anemia, workup for the underlying etiology and iron repletion should be performed.
A diagnosis of iron deficiency in heart failure is made if the ferritin is <100mcg/L or ferritin between 100-300mcg/L with TSAT <20%.
In patients with CHF, iron deficiency with or without anemia should be treated with IV iron. Intravenous iron Is preferred over oral iron due to limited absorption of oral iron and limited evidence available on the efficacy oral iron supplements. Intravenous iron has been shown to improve exercise tolerance and health related quality of life. (2)
Inflammatory Bowel Disease (IBD)
Due to the gastrointestinal mucosal injury and associated inflammation, iron deficiency and iron deficiency anemia affects a significant proportion of individuals with IBD.
IV iron is the first line treatment in IBD as many individuals will have intolerance to oral iron supplements, the inflammation and malabsorption in active disease will interfere with iron absorption, and there is evidence demonstrating the safety and efficacy of different IV iron formulations in IBD. (3) There is evidence that oral iron supplements may increase disease activity. (4)
Preoperative Anemia
Approximately 23%-45% of patients undergoing major surgery have anemia, most commonly secondary to iron deficiency or anemia of inflammation. (5)
Preoperative anemia is associated with poor outcomes, including increased length of hospital stay, requirement of RBC transfusions, postoperative anemia, and mortality.
There is evidence that a hemoglobin level of 130 g/L or higher should be targeted for both sexes before surgery in order to minimize risk of poor outcomes and transfusions. (6)
Patients undergoing elective surgery with expected blood loss >500ml should be screened for anemia 6-8 weeks prior to the surgery and be treated with oral iron at equivalent doses of 40-60mg daily if anemia is present. If surgery lead time is less than 6 weeks, or patient was unable to tolerate oral iron, intravenous iron is recommended. (6)
Chronic Kidney Disease
IV iron is considered the current standard in both dialysis- and non-dialysis-associated chronic kidney disease. This is due to impaired iron absorption, frequent use of calcium-containing salts and antacids, synergism with erythropoiesis stimulating agents, and IV iron results in higher hemoglobin concentrations.
In patients with CKD and anemia, iron replacement therapy is indicated if ferritin is less than 500 μg/L and a transferrin saturation is less than 30 %. There are multiple guidelines regarding management of iron deficiency in CKD, one of which is the Kidney Disease: Improving Clinical Outcomes (KDIGO) 2012 guidelines.
Pregnancy
Anemia affects approximately 40% of pregnant females, mostly due to iron deficiency.
In a recent study conducted at St. Michael’s Hospital in Toronto, among 1307 pregnant patients, 81% had iron deficiency (defined by a serum ferritin level <30 ug/L) and 24% had iron deficiency anemia (IDA) (defined by a ferritin <30 ug/L with a hemoglobin concentration <110g/L). (9)
Pregnancy increases the risk of iron deficiency due to increased iron requirements related to fetal growth, increased maternal RBC mass, and blood loss during delivery.
Iron deficiency and anemia during pregnancy are associated with higher risk of blood transfusions, preterm birth, low birth weight, and potential neonatal neurocognitive aberrations. (10)
Screening & Diagnosis for Iron Deficiency in Pregnancy
There is data suggesting suboptimal anemia and iron deficiency screening in Ontario. (11) Therefore, it is suggested that all pregnant females should be screened in the first prenatal visit with a CBC and ferritin.
Anemia during pregnancy is diagnosed when the Hb is ≤ 110 g/L in the first trimester, <105 g/L in the second trimester, and <110 g/L in the third trimester. Iron deficiency is defined as serum ferritin <30 µg /L, although there is evidence that serum ferritin <50 µg/L is in keeping with iron insufficiency in adults. (12)
Treating Iron Deficiency in Pregnancy
Oral iron the first line therapy for iron deficiency with or without anemia, with iron salts (ferrous gluconate, sulfate or fumarate) recommended as first line, as they less expensive and there is no evidence the more expensive counterparts are more effective.
It is important to note that oral iron may not be tolerated by some women during pregnancy due to the gastrointestinal side effects, which are worse during pregnancy due to the enlarging uterus and elevated progesterone levels decreasing bowel motility.
Intravenous iron is recommended for all gravidas who are the second or third trimester with severe anemia, symptomatic, unable to tolerate oral iron, or there is concern for impaired absorption of oral iron.
There is no evidence that one formulation is safer or more efficacious than the other, however, there is a likely benefit of providing larger dose formulations because of the decreased healthcare resources required and reduced burden of frequency of hospital visits on the patients. There is evidence of reluctance of physicians to use IV iron in pregnancy due to the concern of maternal hypersensitivity reactions and fetal complications, however these were associated with older formulation that are no longer available, and guidelines continue to recommend use of IV iron after the first trimester when indicated. (13)
A Suggested Approach for the Management of Iron Deficiency in Pregnancy
Preventing Iron Deficiency in Pregnancy
To prevent iron deficiency, pregnant females should take 27-30 mg of supplemental oral iron daily, which is supplied in most iron-containing prenatal vitamins.
Given that prenatal vitamins contain divalent cations, which decrease iron absorption, they may not be sufficient if there are risk factors for iron deficiency present, and they should be taken at a separate time from oral iron supplements.
It may also be reasonable to continue the prenatal vitamin and/or supplemental iron for six to eight weeks following delivery.
