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Update on Iron Deficiency Anemia in Gastrointestinal Disorders

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Annual Scientific Meeting of the American College of Gastroenterology

San Diego, California / October 11-16, 2013

San Diego - Iron deficiency anemia (IDA) is widely prevalent among patients with gastrointestinal disease, mainly due to chronic blood loss as a result of mucosal damage, reduced duodenal absorption of dietary iron, and/or reduced dietary intake of iron. Numerous oral iron and newer intravenous non-dextran formulations are available for treatment. Individuals with inflammatory bowel disease are known to have a higher incidence of depression, but symptoms of depression are not thought to be a result of underlying anemia. Proton pump inhibitors can increase gastric pH and impact iron absorption. IDA may also result from rare gastrointestinal malignancies.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Iron deficiency anemia (IDA), the most common form of anemia worldwide, is diagnosed when patients present with low hemoglobin (Hb; <13 g/dL in men or <12 g/dL in women), transferrin saturation (<20%), and ferritin concentrations (Reinisch W et al. J Crohns Colitis 2013;7:428-40). Gastrointestinal (GI) disorders are the main cause of IDA in men and in postmenopausal women, whereas in premenopausal women, most IDA is due to menstrual blood loss and pregnancy-related iron losses. Although mild IDA is asymptomatic, when it becomes more severe, patients experience an overall decrease in quality of life (QoL), with fatigue, dyspnea, low energy, exercise intolerance, reduced vitality, and reduced cognitive abilities. Due to these non-specific symptoms, IDA is commonly underdiagnosed and undertreated.

Among men and women with inflammatory bowel disease (IBD), the prevalence of IDA has been reported as ranging from 6% to 74% (Kulnigg S et al. Aliment Pharmacol Ther 2006;24:1507-23). Oral iron supplementation is commonly used as first-line treatment, with ferrous fumarate, sulfate, and gluconate formulations being the most commonly prescribed.  However, current guidelines suggest that iron supplementation in IBD should be administered intravenously, especially in patients with severe anemia (Hb <10 g/dL), intolerance, or inappropriate response to oral iron supplements (Gasche C et al. Inflamm Bowel Dis 2007;13:1545-53; Stein J et al. Nat Rev Gastroenterol Hepatol 2010;7:599-610).

Expansion of IV Iron Therapy

Ferric carboxymaltose and ferumoxytol, two IV iron therapies used to treat IDA, have been studied in the treatment of IDA related to GI disorders (Kent AJ et al. Curr Drug Deliv 2012;9:356-366.; Goldberg ND. Clin Exp Gastroenterol 2013;6:61-70) .

Presented here (Dahl N et al. Am J Gastroenterol 2013;108:S469. Abstract 1567) and based on a post-hoc analysis of patients experiencing IDA as a result of a GI disorder, the subgroup showed similar improvements in Hb and health-related QoL as seen in the main study (Vadhan- Raj S et al. Am J Hematol Published online August 26, 2013). The prespecified subgroup consisted of 231 patients with IBD (25%), gastric bypass surgery (25%), or other ongoing GI bleeds, and a mean Hb of <9 g/dL, despite prior oral iron. By Week 5, Hb was increased by 2.8 g/dL with ferumoxytol compared with no increase (-0.1 g/dL) in the patients on placebo (P<0.05). Mean FACIT-Fatigue score, which the investigators noted was around 22 at baseline and comparable with anemic cancer patients receiving chemotherapy, rose quickly in parallel with the Hb increase in patients receiving treatment, attaining an increase of 11.1 points compared with 7.5 points with placebo (P<0.05). Similar changes were seen in 7 of the 8 Short-Form Health Survey (SF-36) health domains (P<0.05). Improvements in Linear Analogue Scale Assessment (LASA) domains were also generally parallel to those seen in the main study, the investigators added.

IDA and Psychiatric Disorders

Individuals with IBD are known to be at increased risk for depression, with a reported 3-fold higher prevalence than that of the general population (Fuller-Thomson E et al. Inflamm Bowel Dis 2006;12:697–707). However, depression and other psychiatric disorders in IBD patients do not appear to be associated with IDA, according to a new study (Panara A et al. Am J Gastroenterol 2013;108:S559. Abstract 1852). Dr. Andres J Yarur, University of Miami, Leonard M. Miller School of Medicine, Florida, reported a retrospective, cross-sectional analysis of data from 621 patients with Crohn’s disease or ulcerative colitis followed in the GI clinic at the University of Miami and Jackson Memorial Hospitals between 2006 and 2011. “We were seeing many patients in our clinic who were on antidepressants and benzodiazepines and we wanted to see whether this higher prevalence of depression, anxiety, and psychotropic use was due to their iron deficiency or anemia,” he explained.

Among the study patients, who were actively treated for their anemia with oral or IV iron, 18.6% had a formal diagnosis of depression and 26.7% had anxiety, and 22% received ≥1 psychotropic drug, with benzodiazepines the most commonly prescribed (14%). After multivariate analysis, only female gender and duration of IBD >10 years remained significant for risk of psychotropic use; anemia (Hb <9 g/dL)
and diagnosis of severe anemia were not significant. “Our main conclusion is that we do not believe that the symptoms of depression are explained by the anemia,” Dr. Yarur stated.

Proton Pump Inhibitors and Anemia

Proton pump inhibitors (PPIs) are widely prescribed to treat gastrointestinal diseases, but it is known that over the long-term, PPIs can increase gastric pH, which may negatively impact the absorption of iron in the duodenum. “This would be particularly important for patients being treated with both a PPI and iron-replacement therapy,” noted Dr. Rezwan Ahmed, Marshall University School of Medicine, Huntingdon, West Virginia.

Dr. Ahmed presented the results of a retrospective chart review of 200 patients who had a capsule endoscopy (CE) for various indications, including IDA, melena, and IBD, between January 1, 2007, and December 30, 2012 (Ahmed R et al. Am J Gastroenterol 2013;108:S598. Abstract 1968). Fifty-two patients were found to have an indication for IDA, 26 of whom had been taking a PPI prior to the study for an average duration of 570 days. Sixteen (61.5%) of these patients had their PPI terminated after the study. “Interestingly, after iron supplementation, these patients were found to have a stable and improved hemoglobin level 12 months after the CE,” Dr. Ahmed said. “We believe that the results of our study represent an important association between PPI use and isolated IDA,” he declared. “The message is that prescribers should be more judicious whenever they are prescribing a long-term PPI in their patients,” he stressed. “Although the link has been looked at in the mainstream GI community for some time, no one has done a large-scale study and this suggests that there needs to be more research on it.”

Rare Gastrointestinal Malignancies

Asymptomatic colonic and gastric carcinoma may also present with IDA, especially in men and postmenopausal women. Physicians from Chicago reported a rare case of primary colonic mucosa-associated lymphoid tissue (MALT) lymphoma in a 53-year-old woman who presented with diabetes, hypertension, congestive heart failure and asymptomatic IDA (Sheth N et al. Am J Gastroenterol 2013;108:S274-5. Abstract 920). “Less than 5% of primary colonic lymphomas are of the MALT subtype, amounting to less than 0.1% of all colorectal malignancies,” noted Dr. Neil Sheth, John H. Stroger Jr. Hospital of Cook County, Chicago IL, adding that the disease typically follows an indolent course with excellent 5-year survival rates of 85-100%. However, the relapse rate in non-gastric MALT lymphoma is around 50%, emphasizing the need for lifelong follow-up in these patients.

Another rare case reported at the meeting was an enterogenous cyst causing intussusception and iron IDA in a 34-year-old male (Shar N et al. Am J Gastroenterol 2013;108. Abstract 1044). Enterogenous cysts are usually detected during infancy or childhood, noted US researchers led by Dr. Nihar Shar, Saint Joseph Regional Medical Center, Bloomfield, New Jersey. The patient, who had no past medical history presented with diffuse intermittent abdominal pain for 3 months and a 10 lb weight loss. Outpatient blood work up showed IDA and fecal occult blood was positive. Outpatient esophagogastroduodenoscopy done to further investigate the cause of IDA, showed non-erosive gastritis. CT scan showed distal small bowel intussusception. After symptoms worsened, laparoscopic exploration showed a large mass with an area of intussusception in the mid ileum. A small incision was made and the affected portion was resected and anastomosed. The patient’s postoperative course was uneventful and he remained asymptomatic at 2 weeks following hospital discharge, Dr. Shar and his colleagues reported.

Summary

With GI disorders being the most likely cause of IDA in men and in postmenopausal women, gastroenterologists need to become more directed toward the diagnosis and treatment of IDA. With IV iron products becoming available, the choice of therapy and opportunity to improve patient QoL for those suffering from IDA associated with GI disorders, who are unable to tolerate or are unresponsive to oral iron therapy, should improve.  

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