Recognizing Concomitant Anemia Secondary to Digestive Diseases
Conditions of the digestive tract are some of the most common ailments that can cause anemia, including inflammatory bowel disease (IBD), hepatitis C, ulcerative colitis, Crohn’s disease, ulcers, celiac disease, bleeding and post-operative conditions such as resection of the ileum, total gastectomy and gastric bypass surgery. Specifically, patients with ulcerative colitis or Crohn’s disease are readily affected by anemia caused by iron deficiency at the rates of 81-95% and 39%, respectively.1,2 Anemia due to chronic inflammation has also been shown to occur in about 10% of patients with IBD3 and about 50% of Crohn’s disease patients.4 As a signal of these conditions, anemia and its related symptoms can be one of the earliest indicators.
Managing anemia is an important step in providing thorough treatment to patients with GI conditions. Studies show that inflammatory bowel disease (IBD) patients with anemia display an increased morbidity in the form of weakness, dyspnea and clinical disease activity.5 Across a variety of conditions – including IBD – iron deficiency anemia and anemia due to any cause have also been associated with increased mortality.6,7
Conditions of the Gastrointestinal Tract Causing Anemia
Although anemia symptoms and the mechanisms at work can provide some insight, a correct diagnosis of the underlying condition can still be illusive. Dr. Vincent Panella, a gastroenterologist at the Englewood Hospital and Medical Center, contends “Sometimes the cause can be very obvious - other times confusing. For example, celiac sprue might not be diagnosed for months or years because it is not readily thought of.” Regardless of their prominence or prevalence, there are several chronic illnesses, infections, and surgical procedures involving the GI tract which can cause anemia, including the following:
Inflammatory Bowel Disease (IBD) – Multiple factors occurring in patients with IBD can lead to the development of anemia, including blood loss, inadequate nutrient intake or absorption, and the underlying inflammatory disease process.8 The two main types of IBD are ulcerative colitis, limited to the colon, and Crohn’s disease, affecting the entire GI tract from the mouth to the anus.9 Anemia has been reported present in 8-74% of ulcerative colitis patients, 10-72% of Crohn's disease patients, and 17-41% in the more than 1 million IBD patients in the United States.8
Hepatitis C – Hemolytic anemia can occur as a side effect of taking the oral antiviral agent ribavirin, which along with interferon, is part of approved combination therapy for hepatitis C virus (HCV).10 Although more effective than interferon singularly, ribavirin causes red blood cell hemolysis and can lead to necessary dose reductions in 7-9% of patients on combination therapy.11,12 Roughly 4.1 million patients in the United States have antibodies to fight an ongoing or previous HCV infection.10
Ulcers – Iron deficiency anemia can develop as a result of blood loss from a disruption in the protective lining of the GI tract, most often from a H. pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDS).13 The anti-inflammatory medications aspirin, ibeuprofin and naproxen, commonly administered for arthritis and pain, can also contribute to the development of ulcers and lacerations.
Celiac Disease (Sprue) – Celiac disease is an inherited, autoimmune disease affecting the lining of the small intestine. Without dietary adjustments or treatment, damage to the intestinal villi from consuming gluten found in grain products can affect absorption of nutrients in the intestine.14,15 Decreased absorption of folate, vitamin B12 or iron leads to vitamin or iron deficiency anemia in about 10-15% of patients.15
Post-operative Conditions – Anemia can also occur following gastric bypass surgery, total gastrectomy and resection of the ileum due to decreased iron or vitamin absorption. Entire sections of the GI tract may be bypassed or removed in these procedures to treat various gastric conditions and malignancies. Patients receiving a gastric bypass will most certainly develop iron deficiency anemia due to malabsorption without iron therapy following the procedure. Similarly, anemia from vitamin B12 deficiency may occur in the years following a total gastrectomy when the body’s stores are finally exhausted.
Mechanisms Leading to Anemia
|Blood Loss||Reduced Nutrient Absorption||
Important Questions to Ask Your Patients Chronic symptoms can herald iron deficiency anemia or anemia of chronic disease; making it important to ask your patients:
- Are you experiencing weight loss or fatigue?
- Have you been unusually thirsty or had cravings for ice?
- If you have had diarrhea, is it bloody or accompanied by fever, and how long has it been occurring?
Conditions of the GI tract can cause anemia through a variety of mechanisms, including blood loss, reduction of nutrient absorption, the underlying inflammatory disease process, and as a result of taking certain medications. The mechanisms resulting in patients presenting with anemia are not uniquely attributable to any one condition of the GI tract, but their presence can narrow the possible diagnoses.
Blood Loss – The loss of blood is a common reason patients develop iron deficiency and iron deficiency anemia (IDA). In the United States, IDA is considered the hallmark of a chronic condition with continued blood loss. For women of childbearing age, iron deficiency and IDA are regularly the result of menstrual bleeding, and less frequently caused by GI bleeding. For male patients, however, the presence of IDA and evidence of blood in the stool should indicate a malignancy of the GI tract until proven otherwise. Chronic blood loss, often occult, can occur in patients with IBD, ulcers or weak tangled blood vessels called arteriovenous malformations (AVMs). If the results from a complete blood count (CBC) indicate that a patient is found to be anemic and additional testing indicates their iron levels are low, a fecal occult blood test should be completed to check for blood in the stool.
Reduced Nutrient Absorption – Because nutrient absorption is an integral function of the gastrointestinal tract, many GI conditions can adversely affect the intake of nutrients necessary for producing healthy red blood cells. Insufficient iron stores or a lowered supply of folate or vitamin B12 can regularly lead to deficiency-related anemias. Without the presence of enough of these nutrients, red blood cells malformations can be observed. Small, microcytic cells can indicate IDA, evidence of a hereditary condition called thalessemia (also known as Cooley’s Anemia) or the rare occurrence of sideroblastic anemia. Large, macrocytic cells can indicate a vitamin B12 deficiency or alcohol use, which deforms the red blood cell membrane causing it to stretch and become larger.
Inflammation – The body’s natural inflammatory responses can decrease the production of red blood cells, causing depressed hemoglobin levels. Anemia due to prolonged inflammation, also known as anemia of chronic disease (ACD), occurs when increased levels of cytokines impair the production of erythropoietin (EPO) – the hormone which triggers red blood cell production in the bone marrow. All chronic conditions with an increased inflammatory response have the potential to lower hemoglobin levels and potentially cause anemia.
Medications – Some medications and treatments can lead to anemia by either interfering with red blood cell production or irritating the lining of the GI tract. The use of the hepatitis C medication ribavirin, nonsteroidal anti-inflammatory drugs (NSAIDS), and other anti-inflammatory drugs should be monitored for these side effects.
Concurrently Managing Anemia and the Ailment
While anemia may be causing patients to feel tired and immediate treatment may alleviate some symptoms, Dr. Panella stresses that, “It is very important to investigate the reason a patient is iron deficient and not to just treat the anemia by itself. The most important thing is to find the cause of anemia.”
Once the underlying illness can be indentified in anemic patients, the condition and anemia should then be managed concurrently. Early detection of anemia can also help avoid increased morbidity, leading to shorter and simpler treatments of iron supplementation, vitamin supplementation, administration of erythropoiesis-stimulating agents (ESAs) or transfusions. Immunosuppressive agents may also help heal inflamed tissues and reduce blood loss. Simply treating the anemia or iron deficiency alone may not address the ultimate reason iron stores are decreased or red blood cell production is depressed.
Working With Patients
To effectively manage both a GI condition and the resulting anemia, primary care physicians and gastroenterologists must pay close attention to the knowledge patients can impart about their symptoms and state of their health.
“It's important to have a good rapport with your patients since most diagnoses are made by taking a careful, complete history,” commented Dr. Panella. “Obtaining that history is made easier and is more effective when the patient feels comfortable while speaking and the physician is good at listening.”
Working closely with patients and encouraging them to report their symptoms can greatly increase your ability to effectively diagnose and treat GI conditions and concomitant anemia.
- Gasché C, Dejaco C, Reinisch W, Tillinger W, Waldhoer T, Fueger GF, Lochs H, Gangl A. Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin. Digestion. 1999;60(3):262-67. Link.
- Driscoll RH Jr, Rosenberg IH. Total parenteral nutrition in inflammatory bowel disease. Med Clin North Am. 1978 Jan;62(1):185-201. Link.
- Christodoulou DK, Tsianos EV. Anemia in inflammatory bowel disease - the role of recombinant human erythropoietin. Eur J Intern Med. 2000 Aug;11(4):222-27. Link.
- Dohil R, Hassall E, Wadsworth LD, Israel DM. Recombinant human erythropoietin for treatment of anemia of chronic disease in children with Crohn's disease. J Pediatr. 1998 Jan;132(1):155-59. Link.
- Schreiber S, Howaldt S, Schnoor M, Nikolaus S, Bauditz J, Gasché C, Lochs H, Raedler A. Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease. N Engl J Med. 1996 Mar 7;334(10):619-23. Link.
- McCullough PA, Lepor NE. The deadly triangle of anemia, renal insufficiency, and cardiovascular disease: implications for prognosis and treatment. Rev Cardiovasc Med. 2005;6:1–10. Link.
- Cucino C, Sonnenberg A. Cause of death in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2001 Aug;7(3):250-55. Link.
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- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Chronic hepatitis C: current disease management. National Digestive Diseases Information Clearinghouse. Link.
- Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet. 1998 Oct 31;352(9138):1426-32. Link.
- McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998 Nov 19;339(21):1485-92. Link.
- EMedicine. Gastric Ulcers. Link. Accessed: June 4, 2009.
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- Green PH, Cellier C. Celiac disease. N Engl J Med. 2007 Oct 25;357(17):1731-43. Link.
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