Author : Dr Don Rockey Duke University Medical Center Durham
2008-07-28
2008-07-28
OVERVIEW
Occult gastrointestinal bleeding is the most common form of gastrointestinal bleeding and generally presents in the two following clinical scenarios: (1) iron deficiency anemia and, (2)fecal occult blood . Both of these forms of bleeding are unrecognized by the patient, and thus are referred to as “occult” bleeding. The latter is becoming less common since fecal occult blood testing is becoming less common in clinical medicine. However, iron deficiency anemia, the result of chronic blood loss, is the most common form of anemia encountered in the world. In the U.S., iron deficiency anemia is most common in children and women of child-bearing age and/or who have become pregnant. From the perspective of the gastrointestinal tract, current dogma is that in men and postmenopausal women with iron deficiency anemia, gastrointestinal tract pathology is the likely source of blood loss, and that is where evaluation is generally focused. Obscure gastrointestinal bleeding refers to bleeding that is obvious to the patient, but comes from a lesion in the gastrointestinal tract that is difficult to identify, although many appear to emanate from the small bowel. Obscure gastrointestinal bleeding will not be reviewed here.
The potential frequency of occult gastrointestinal bleeding is emphasized by the observation that approximately 150 to 200 mL (an amount equivalent to a regular sized glass of water) of blood must be placed in the stomach to consistently produce visible evidence of blood in the stool (i.e., melena or black tarry stools). Additionally, patients with gastroduodenal bleeding of up to 100 mL per day may have normal appearing stools. Thus, occult bleeding is often only identified by special tests that detect fecal blood, or, if bleeding occurs for a long enough period of time, it may become manifest by iron depletion and anemia.
IRON DEFICIENCY ANEMIA
In the United States alone, some 5-11% of adult women and 1-4% of adult
men are iron deficient; approximately 5% and 2% of adult women and men,
respectively, have iron deficiency anemia. Iron deficiency anemia is
defined by the presence of anemia and low iron stores (see below). On
occasion, patients may have iron deficiency without anemia, though by
definition, anemia will develop in the iron deficient state as long as
blood loss continues without iron replacement. Iron deficiency anemia
is most common in women during their reproductive years because of
menstrual and pregnancy-associated blood losses. However, in
non-menstruating women and men, iron deficiency anemia has traditionally
been assumed to be caused by chronic occult gastrointestinal bleeding.
How does iron deficiency anemia develop?
Iron balance is tightly regulated under normal physiologic conditions (Figure 1). Iron absorption is also normally tightly regulated. Under normal circumstances, the small amount of iron lost from the stool (usually in sloughed intestinal cells or by tiny amounts of bleeding) is approximately 1 mg per day. Iron deficiency results when the absorptive capacity of the small intestine (which increases to a maximum of 2-4 fold above normal) is exceeded by iron loss over a prolonged period of time. It is clear that it takes considerable time (several months at the very least) to exhaust the normal body stores of iron. However, this happens frequently when specific lesions in the gastrointestinal tract bleed as little as several mL of blood per day.
Definition of iron deficiency anemia
The diagnosis of iron deficiency and iron deficiency anemia should be considered any time that a low serum hemoglobin level or hematocrit is encountered. A reduced mean corpuscular volume (MCV) supports the diagnosis, but is not definitive. Iron deficiency anemia is best confirmed by documenting a low serum ferritin level in the setting of anemia (Hgb less than 11.5 mg/dL for women and 12.5 for men). A very low ferritin level (less than 20 ng/mL) is essentially diagnostic of iron deficiency anemia. Since a diagnosis of iron deficiency anemia in postmenopausal women or men will lead to extensive and often costly evaluation, it is important that the diagnosis of iron deficiency anemia be carefully established.
What are the specific causes of occult bleeding that may lead to iron deficiency anemia?
Common teaching used to be that iron deficiency anemia was usually caused by colon cancer, especially lesions in the right colon, because their bleeding can remain undetected for long periods of time. However, many studies have now documented that occult bleeding can occur as a result of a lesion (or lesions) from virtually anywhere in the gastrointestinal tract (and even from the oral cavity or nasopharyngeal area) (Table 1). Indeed, iron deficiency anemia is not uncommonly caused by an abnormality found in the upper gastrointestinal tract. Particularly common are severe ulcerative processes in the upper gastrointestinal tract (esophageal/gastric/duodenal ulcer). A number of other lesions can bleed chronically and also cause iron deficiency anemia. The most common cause of iron deficiency anemia worldwide is probably hookworm, (see http://www.cdc.gov/NCIDOD/dpd/parasites/hookworm/factsht_hookworm.htm) because these small parasites are capable of removing significant amounts of blood from the colon on an ongoing basis.
A critical issue in managing patients with iron deficiency anemia is that the clinician must appropriately correlate gastrointestinal lesions with the degree of blood loss. For example, although it is clear that mass lesions and severe ulcerative upper gastrointestinal lesions can lead to substantial blood loss (up to 20 mL per day), which can readily cause iron deficiency anemia, it is unlikely that trivial lesions (such as mild inflammation and especially small adenomas) bleed enough to lead to iron deficiency. Thus, judgment must be utilized when linking certain gastrointestinal tract lesions to iron deficiency anemia.
How does iron deficiency anemia develop?
Iron balance is tightly regulated under normal physiologic conditions (Figure 1). Iron absorption is also normally tightly regulated. Under normal circumstances, the small amount of iron lost from the stool (usually in sloughed intestinal cells or by tiny amounts of bleeding) is approximately 1 mg per day. Iron deficiency results when the absorptive capacity of the small intestine (which increases to a maximum of 2-4 fold above normal) is exceeded by iron loss over a prolonged period of time. It is clear that it takes considerable time (several months at the very least) to exhaust the normal body stores of iron. However, this happens frequently when specific lesions in the gastrointestinal tract bleed as little as several mL of blood per day.
Definition of iron deficiency anemia
The diagnosis of iron deficiency and iron deficiency anemia should be considered any time that a low serum hemoglobin level or hematocrit is encountered. A reduced mean corpuscular volume (MCV) supports the diagnosis, but is not definitive. Iron deficiency anemia is best confirmed by documenting a low serum ferritin level in the setting of anemia (Hgb less than 11.5 mg/dL for women and 12.5 for men). A very low ferritin level (less than 20 ng/mL) is essentially diagnostic of iron deficiency anemia. Since a diagnosis of iron deficiency anemia in postmenopausal women or men will lead to extensive and often costly evaluation, it is important that the diagnosis of iron deficiency anemia be carefully established.
What are the specific causes of occult bleeding that may lead to iron deficiency anemia?
Common teaching used to be that iron deficiency anemia was usually caused by colon cancer, especially lesions in the right colon, because their bleeding can remain undetected for long periods of time. However, many studies have now documented that occult bleeding can occur as a result of a lesion (or lesions) from virtually anywhere in the gastrointestinal tract (and even from the oral cavity or nasopharyngeal area) (Table 1). Indeed, iron deficiency anemia is not uncommonly caused by an abnormality found in the upper gastrointestinal tract. Particularly common are severe ulcerative processes in the upper gastrointestinal tract (esophageal/gastric/duodenal ulcer). A number of other lesions can bleed chronically and also cause iron deficiency anemia. The most common cause of iron deficiency anemia worldwide is probably hookworm, (see http://www.cdc.gov/NCIDOD/dpd/parasites/hookworm/factsht_hookworm.htm) because these small parasites are capable of removing significant amounts of blood from the colon on an ongoing basis.
A critical issue in managing patients with iron deficiency anemia is that the clinician must appropriately correlate gastrointestinal lesions with the degree of blood loss. For example, although it is clear that mass lesions and severe ulcerative upper gastrointestinal lesions can lead to substantial blood loss (up to 20 mL per day), which can readily cause iron deficiency anemia, it is unlikely that trivial lesions (such as mild inflammation and especially small adenomas) bleed enough to lead to iron deficiency. Thus, judgment must be utilized when linking certain gastrointestinal tract lesions to iron deficiency anemia.
How should iron deficiency anemia be evaluated?
The standard approach to patients with iron deficiency anemia is to directly evaluate the gastrointestinal tract. The best approach is to examine the gastrointestinal tract mucosa with endoscopy. In the colon, colonoscopy is the best test, and in the upper intestine, esophagogastroduodenoscopy is standard (Colonoscopy these tests are standard, endoscopic, examinations of the bowel; they are performed with endoscopes and are capable of directly visualizing the intestine, either the lower - colonoscopy or the upper - esophagogastroduodenoscopy). Sometimes, routine radiographic tests can be used (barium enema, upper gastrointestinal series), though these have fallen out of favor. Radiographic studies are effective for detecting masses and large ulcerating lesions, but are not very accurate at detecting mucosal lesions.
Some patients with iron deficiency anemia will have gastrointestinal symptoms, while others may not. Symptoms may help focus evaluation to one specific area of the gastrointestinal tract and the evaluation should generally be directed at the source of symptoms. Classic symptoms pointing to the colon include changes in stool caliber (e.g., pencil thin stools or other different shape shapes of stool) or change in bowel habit. In the upper intestine, epigastric pain, early satiety, or poor appetite are of concern. Since synchronous lesions (i.e. lesions in each the upper and lower digestive tract) are rare, identification of an obvious abnormality clearly associated with chronic bleeding (i.e., such as a mass lesion, large ulceration, or severe inflammation) makes further evaluation unnecessary. In the absence of symptoms, particularly in elderly patients, evaluation should begin with the colon, but if this is negative, evaluation of the upper gastrointestinal tract is required.
The small intestine is important to consider as potential site of bleeding in patients with negative examinations of the colon and upper gastrointestinal tract. A number of approaches can be used to examine the small intestine. Endoscopic evaluation of the small intestine has a greater sensitivity for mucosal abnormalities and possibly for mass lesions as well, and therefore has achieved a central position in evaluation of patients who do not present findings in the colon or upper gastrointestinal tract.
In 2008, there are many ways to evaluate the small bowel with endoscopy. The classic form of small bowel endoscopy, known as enteroscopy is usually of the "push" variety. Push enteroscopy consists of insertion of a long endoscope, usually a specialized enteroscope, and should be the initial approach in most patients. Using conscious sedation, the enteroscope can be passed 50 to 60 cm beyond the ligament of Trietz, allowing examination of the distal duodenum and proximal jejunum. Push enteroscopy has been reported to identify a source of bleeding in approximately 25% of patients. More recently, “balloon” enteroscopy has been developed. This form of enteroscopy allows deeper insertion of the endoscope into the small bowel, and thus a larger portion of the bowel can be examined. The major advantages of enteroscopy are that it is relatively safe and that biopsy and endoscopic therapy can be performed.
 |
| Capsule endoscope |
Radiographic examination of the small bowel has been found to be of limited value in patients with iron deficiency anemia and for the most part is not recommended (but of note, enteroclysis remains the best radiographic imaging modality for the small bowel).
A major unresolved issue with small bowel evaluation in patients with iron deficiency anemia has to do with its clinical impact. Although all of the currently available techniques can identify abnormalities in a substantial proportion of patients with iron deficiency anemia (and new diagnoses can be expected), the cost and benefit of these techniques are entirely unknown. Further, whether a small bowel study should be part of initial evaluation for all patients with iron deficiency anemia (and negative colonic and esophagogastroduodenal evaluations) is unresolved.
Other diagnostic approaches may also be contributory. For example, abdominal computed tomography (CT) can identify lesions that endoscopy has failed to detect, in particular neoplastic mass lesions. However, CT is insensitive for detection of mucosal lesions. The most likely diagnoses are highlighted in Table 1.
Special situations
Celiac sprue, a relatively common bowel disorder, is an important cause of iron deficiency anemia and merits special consideration. It can lead not only to malabsorption of iron, but may also cause occult bleeding and should be ruled out in most patients with iron deficiency anemia. Celiac sprue is particularly common in patients of Northern European descent and the elderly. Of note, celiac disease may be uncommon in patients of certain ethnic backgrounds such as those of Hispanic origin. A high index of suspicion is often required to make the diagnosis; therefore, small bowel biopsies should be routinely obtained in patients without another obvious cause of iron deficiency anemia.
Gastritis, either of the atrophic variety, or caused by Helicobacter pylori may be an important cause of iron deficiency anemia, presumably due to iron malabsorption.
Many patients with iron deficiency anemia have no identifiable gastrointestinal tract abnormality after appropriate gastrointestinal evaluation. In this circumstance, explanations for iron deficiency anemia include non-gastrointestinal blood loss, misdiagnosis of the type of anemia, missed lesions, or nutritional deficiency. A management algorithm for evaluation of iron deficiency anemia is shown in Figure 3.
Treatment and outcome
Once the diagnosis of iron deficiency anemia has been confirmed, iron therapy should be instituted. Oral ferrous sulfate is recommended because it is inexpensive and effective (the recommended dose is 300 mg/three times daily). In those who are intolerant to ferrous sulfate, ferrous gluconate or fumarate are acceptable alternatives. Parenteral iron therapy should be used only for patients who have severe malabsorption or who are intolerant to iron supplements.
Specific management of patients with iron deficiency anemia depends on the underlying disorder responsible for the bleeding. Most mass lesions require surgical excision, while ulcerative processes can usually be managed with medical therapy. If patients are taking non-steroidal anti-inflammatory drugs, these should be discontinued, even if a lesion cannot be identified. The prognosis for patients with iron deficiency anemia and lesions amenable to medical therapy (i.e., duodenal ulcer, esophagitis, large adenoma) is excellent.
Perhaps the most challenging patients are those with vascular ectasias; these lesions are usually multiple, may be difficult to identify, and bleed recurrently, making management difficult. In addition, treatment of one lesion does not preclude bleeding from another. Patients with lesions that are readily identified are best treated endoscopically with some form of thermal-based treatment (laser, bipolar electrocoagulation, bicap, or argon plasma coagulation) or banding or injection therapy; each of these techniques appears to be effective and relatively safe. For diffuse ectasias, the use of pharmacologic therapy with estrogen/progesterone compounds is controversial. Other agents, including aminocaproic acid, tranexamic acid, and danazol may be helpful, but again controlled data are not available.
The prognosis for patients who do not have lesions identified during gastrointestinal evaluation is favorable; very few are found to have significant gastrointestinal lesions at a later date. The majority of patients with iron deficiency anemia and no identifiable gastrointestinal tract lesion respond to standard oral iron therapy. For patients who do not respond to iron therapy, the diagnosis of iron deficiency anemia should be re-evaluated and repeat gastrointestinal evaluation should remain an important consideration.
FECAL OCCULT BLOOD
Fecal occult blood is an extremely common form of occult gastrointestinal bleeding. However, because the use of fecal occult blood tests has been declining (due to the wider acceptance of other screening tools such as colonoscopy), the finding of a positive fecal occult blood test is becoming less frequent. Nonetheless, fecal occult blood tests are effective tools with which to screen the colon for cancer.
Fecal blood loss in normal individuals varies from 0.5 to 1.5 mL per
day. The likelihood of detecting fecal blood depends on the type of
fecal occult blood test used as well as individual characteristics -
including the frequency with which the bleeding lesion bleeds, bowel
motility, and the anatomic level of bleeding (Figure 4).
Guaiac-based tests
Guaiac-based fecal occult blood tests have been the most commonly used. Guaiac-based tests take advantage of the fact that hemoglobin possesses pseudoperoxidase activity; guaiac turns blue after oxidation by oxidants or peroxidases in the presence of an oxygen donor such as hydrogen peroxide. Guaiac tests are more sensitive for detecting bleeding from the lower than upper gastrointestinal tract since hemoglobin is degraded in the gastrointestinal tract (Figure 4).
A variety of factors influence guaiac test results. For example, fecal rehydration affects the reactivity of guaiac-based tests; it raises sensitivity, but reduces specificity 45. Additionally, diet is important, because foods that contain peroxidases can cause (false) positive guaiac test results. It is commonly believed that oral iron causes positive guaiac tests. However, the dark-green or black appearance of iron in stool should not be confused with the blue typical of a positive guaiac reaction. Finally, bismuth containing antacids and anti-diarrheals cause the stool to darken and should not be confused with a positive guaiac reaction.
Immunochemical-based tests
Immunochemical fecal occult blood tests detect human globin epitopes and are highly sensitive for detection of human blood. Further, they do not detect blood from upper gastrointestinal sources (Figure 4) because globin molecules are degraded by enzymes found in the upper gastrointestinal tract. They therefore have a theoretical advantage over guaiac-based tests in terms of specificity for detection of colonic lesions.
Heme-porphyrin based tests
The heme-porphyrin test (HemoQuant, Mayo Medical Laboratories, Rochester, MN) relies on a spectrofluorometric method to measure porphyrin derived from heme, and therefore provides a highly accurate determination of total stool hemoglobin. Although neither intraluminal degradation of hemoglobin nor interfering peroxidase producing substances affect the heme-porphyrin assay, an important problem with this test is myoglobin, a heme containing protein found in red meats that will be measured as heme-porphyrin.
Causes and evaluation of patients with fecal occult blood
The history and physical examination can provide information important to the clinician when considering differential diagnosis. As above for iron deficiency anemia, the focus should first be on gastrointestinal symptoms. Additionally, a history of medications that can injure the gastrointestinal mucosa, including NSAIDs, alendronate, and potassium chloride should be sought. Use of anticoagulants is also relevant.
As with iron deficiency anemia, essentially any gastrointestinal lesion can lead to occult bleeding and positive fecal occult blood tests, including lesions that are often associated with acute bleeding (Table 1). Although the colon has traditionally been considered to be the source of most occult gastrointestinal blood loss, the upper gastrointestinal may also be the source of occult bleeding.
In asymptomatic patients found to have occult blood in the stool, investigation should initially be focused on the colon (Figure 3). Colonoscopy is the recommended test (although barium enema has been used in some cases). Recently, CT colonography has been introduced as an alternative method to evaluate the colon. However, given the likelihood that a lesion requiring some form of therapy (polyp) will be found, colonoscopy, which permits biopsy and therapyit is preferred. The choice of evaluation will vary, depending on local expertise, comfort of the patient with a specific test, and test availability.
In patients with gastrointestinal symptoms that suggest specific diagnoses (i.e., change in stool caliber, epigastric pain, or heartburn) initial investigation should generally be directed toward the location of specific symptoms.
Occult gastrointestinal bleeding may be attributed to anticoagulant or aspirin therapy. However, it has been demonstrated that fecal blood levels in patients therapeutically anticoagulated are normal. Low dose aspirin alone does not seem to cause elevations in fecal blood levels. Thus, a positive fecal occult blood test should not be attributed to anticoagulation or aspirin alone, but rather, should raise the possibility of a gastrointestinal tract abnormality.
Management of patients with fecal occult blood
As with iron deficiency anemia, management of patients with fecal occult blood depends on the underlying etiology of bleeding. General recommendations for management are as above for iron deficiency anemia. The prognosis of patients with positive fecal occult blood tests, but no identifiable gastrointestinal pathology, appears to be favorable, but this has not been rigorously studied.
Summary of occult gastrointestinal bleeding
Both iron deficiency anemia and/or fecal occult blood are frequently encountered in routine clinical practice – thus, occult gastrointestinal bleeding is very common. Iron deficiency anemia results from ongoing occult gastrointestinal bleeding. Evaluation of asymptomatic patients with iron deficiency anemia or fecal occult blood should usually begin with investigation of the colon. Colonoscopy is the preferred method to evaluate the colon, but other approaches (i.e., such as flexible sigmoidoscopy and/or radiologic imaging of the colon) may be acceptable in certain circumstances. If evaluation of the colon does not reveal a bleeding site, evaluation of the upper gastrointestinal tract is mandatory in patients with iron deficiency anemia, and should be considered in those with fecal occult blood. In patients with gastrointestinal symptoms, evaluation of the portion of the gastrointestinal tract from which the symptoms are emanating should be considered. The role of small intestine investigation in patients with iron deficiency anemia is controversial, but is probably best reserved for patients with persistent iron deficiency anemia (i.e., refractory to iron treatment), or those with persistent gastrointestinal symptoms. Celiac sprue should be considered as a potential cause of iron deficiency anemia in all patients. The treatment and prognosis of patients with iron deficiency anemia and/or fecal occult blood depends on the gastrointestinal tract abnormality(ies) identified. Those without identifiable bleeding sites generally respond to conservative management and have a favorable prognosis. On the other hand, the outlook is poorer for patients with refractory occult blood loss and/or those who have vascular ectasias. Both of these groups of patients are clinically challenging and require an experienced approach.
SELECTED READING
Bini EJ, Rajapaksa RC, Weinshel EH. The findings and impact of nonrehydrated guaiac examination of the rectum (FINGER) study: a comparison of 2 methods of screening for colorectal cancer in asymptomatic average-risk patients. Arch Intern Med 159:2022, 1999
Cave DR. Technology Insight: current status of video capsule endoscopy. Nat Clin Pract Gastroenterol Hepatol 3:158-164, 2006.
Fine KD. The prevalence of occult gastrointestinal bleeding in celiac sprue [see comments]. N Engl J Med 334:1163, 1996.
Green BT, Rockey DC. Gastrointestinal endoscopic evaluation of premenopausal women with iron deficiency anemia. J Clin Gastroenterol 38:104, 2004.
Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 405:417, 2000.
Rockey DC. Occult gastrointestinal bleeding. Gastroenterol Clin North Am 2005;34(4):699-718.
Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. Jama 277:973, 1997.
Rockey DC. Occult gastrointestinal bleeding. N Engl J Med 341:38, 1999.
Rockey DC, Auslander A, Greenberg PD. Detection of upper gastrointestinal blood with fecal occult blood tests. Am J Gastroenterol 94:344, 1999.
Rockey DC, Cello JP. Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia. N Engl J Med 329:1691, 1993.
Rockey DC, Koch J, Cello JP, et al. Relative frequency of upper gastrointestinal and colonic lesions in patients with positive fecal occult-blood tests. N Engl J Med 339:153, 1998.
Schiff L, Stevens RJ, Shapiro N, et al. Observations on the oral administration of citrate blood in man. Am J Med Sci 203:409, 1942.
WEB SITES
Guaiac-based tests
Guaiac-based fecal occult blood tests have been the most commonly used. Guaiac-based tests take advantage of the fact that hemoglobin possesses pseudoperoxidase activity; guaiac turns blue after oxidation by oxidants or peroxidases in the presence of an oxygen donor such as hydrogen peroxide. Guaiac tests are more sensitive for detecting bleeding from the lower than upper gastrointestinal tract since hemoglobin is degraded in the gastrointestinal tract (Figure 4).
A variety of factors influence guaiac test results. For example, fecal rehydration affects the reactivity of guaiac-based tests; it raises sensitivity, but reduces specificity 45. Additionally, diet is important, because foods that contain peroxidases can cause (false) positive guaiac test results. It is commonly believed that oral iron causes positive guaiac tests. However, the dark-green or black appearance of iron in stool should not be confused with the blue typical of a positive guaiac reaction. Finally, bismuth containing antacids and anti-diarrheals cause the stool to darken and should not be confused with a positive guaiac reaction.
Immunochemical-based tests
Immunochemical fecal occult blood tests detect human globin epitopes and are highly sensitive for detection of human blood. Further, they do not detect blood from upper gastrointestinal sources (Figure 4) because globin molecules are degraded by enzymes found in the upper gastrointestinal tract. They therefore have a theoretical advantage over guaiac-based tests in terms of specificity for detection of colonic lesions.
Heme-porphyrin based tests
The heme-porphyrin test (HemoQuant, Mayo Medical Laboratories, Rochester, MN) relies on a spectrofluorometric method to measure porphyrin derived from heme, and therefore provides a highly accurate determination of total stool hemoglobin. Although neither intraluminal degradation of hemoglobin nor interfering peroxidase producing substances affect the heme-porphyrin assay, an important problem with this test is myoglobin, a heme containing protein found in red meats that will be measured as heme-porphyrin.
Causes and evaluation of patients with fecal occult blood
The history and physical examination can provide information important to the clinician when considering differential diagnosis. As above for iron deficiency anemia, the focus should first be on gastrointestinal symptoms. Additionally, a history of medications that can injure the gastrointestinal mucosa, including NSAIDs, alendronate, and potassium chloride should be sought. Use of anticoagulants is also relevant.
As with iron deficiency anemia, essentially any gastrointestinal lesion can lead to occult bleeding and positive fecal occult blood tests, including lesions that are often associated with acute bleeding (Table 1). Although the colon has traditionally been considered to be the source of most occult gastrointestinal blood loss, the upper gastrointestinal may also be the source of occult bleeding.
In asymptomatic patients found to have occult blood in the stool, investigation should initially be focused on the colon (Figure 3). Colonoscopy is the recommended test (although barium enema has been used in some cases). Recently, CT colonography has been introduced as an alternative method to evaluate the colon. However, given the likelihood that a lesion requiring some form of therapy (polyp) will be found, colonoscopy, which permits biopsy and therapyit is preferred. The choice of evaluation will vary, depending on local expertise, comfort of the patient with a specific test, and test availability.
In patients with gastrointestinal symptoms that suggest specific diagnoses (i.e., change in stool caliber, epigastric pain, or heartburn) initial investigation should generally be directed toward the location of specific symptoms.
Occult gastrointestinal bleeding may be attributed to anticoagulant or aspirin therapy. However, it has been demonstrated that fecal blood levels in patients therapeutically anticoagulated are normal. Low dose aspirin alone does not seem to cause elevations in fecal blood levels. Thus, a positive fecal occult blood test should not be attributed to anticoagulation or aspirin alone, but rather, should raise the possibility of a gastrointestinal tract abnormality.
Management of patients with fecal occult blood
As with iron deficiency anemia, management of patients with fecal occult blood depends on the underlying etiology of bleeding. General recommendations for management are as above for iron deficiency anemia. The prognosis of patients with positive fecal occult blood tests, but no identifiable gastrointestinal pathology, appears to be favorable, but this has not been rigorously studied.
Summary of occult gastrointestinal bleeding
Both iron deficiency anemia and/or fecal occult blood are frequently encountered in routine clinical practice – thus, occult gastrointestinal bleeding is very common. Iron deficiency anemia results from ongoing occult gastrointestinal bleeding. Evaluation of asymptomatic patients with iron deficiency anemia or fecal occult blood should usually begin with investigation of the colon. Colonoscopy is the preferred method to evaluate the colon, but other approaches (i.e., such as flexible sigmoidoscopy and/or radiologic imaging of the colon) may be acceptable in certain circumstances. If evaluation of the colon does not reveal a bleeding site, evaluation of the upper gastrointestinal tract is mandatory in patients with iron deficiency anemia, and should be considered in those with fecal occult blood. In patients with gastrointestinal symptoms, evaluation of the portion of the gastrointestinal tract from which the symptoms are emanating should be considered. The role of small intestine investigation in patients with iron deficiency anemia is controversial, but is probably best reserved for patients with persistent iron deficiency anemia (i.e., refractory to iron treatment), or those with persistent gastrointestinal symptoms. Celiac sprue should be considered as a potential cause of iron deficiency anemia in all patients. The treatment and prognosis of patients with iron deficiency anemia and/or fecal occult blood depends on the gastrointestinal tract abnormality(ies) identified. Those without identifiable bleeding sites generally respond to conservative management and have a favorable prognosis. On the other hand, the outlook is poorer for patients with refractory occult blood loss and/or those who have vascular ectasias. Both of these groups of patients are clinically challenging and require an experienced approach.
SELECTED READING
Bini EJ, Rajapaksa RC, Weinshel EH. The findings and impact of nonrehydrated guaiac examination of the rectum (FINGER) study: a comparison of 2 methods of screening for colorectal cancer in asymptomatic average-risk patients. Arch Intern Med 159:2022, 1999
Cave DR. Technology Insight: current status of video capsule endoscopy. Nat Clin Pract Gastroenterol Hepatol 3:158-164, 2006.
Fine KD. The prevalence of occult gastrointestinal bleeding in celiac sprue [see comments]. N Engl J Med 334:1163, 1996.
Green BT, Rockey DC. Gastrointestinal endoscopic evaluation of premenopausal women with iron deficiency anemia. J Clin Gastroenterol 38:104, 2004.
Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature 405:417, 2000.
Rockey DC. Occult gastrointestinal bleeding. Gastroenterol Clin North Am 2005;34(4):699-718.
Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. Jama 277:973, 1997.
Rockey DC. Occult gastrointestinal bleeding. N Engl J Med 341:38, 1999.
Rockey DC, Auslander A, Greenberg PD. Detection of upper gastrointestinal blood with fecal occult blood tests. Am J Gastroenterol 94:344, 1999.
Rockey DC, Cello JP. Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia. N Engl J Med 329:1691, 1993.
Rockey DC, Koch J, Cello JP, et al. Relative frequency of upper gastrointestinal and colonic lesions in patients with positive fecal occult-blood tests. N Engl J Med 339:153, 1998.
Schiff L, Stevens RJ, Shapiro N, et al. Observations on the oral administration of citrate blood in man. Am J Med Sci 203:409, 1942.
WEB SITES
The American Gastroenterological Association
The National Institute of Diabetes and Digestive and Kidney Diseases
The National Institute of Diabetes and Digestive and Kidney Diseases