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Diagnosis and management of lower gastrointestinal bleeding

Jrgen Barnert and Helmut Messmann
Abstract | Lower gastrointestinal bleeding (LGIB) can present as an acute and life-threatening event or as chronic bleeding, which might manifest as iron-deficiency anemia, fecal occult blood or intermittent scant hematochezia. Bleeding from the small bowel has been shown to be a distinct entity, and LGIB is defined as bleeding from a colonic source. Acute bleeding from the colon is usually less dramatic than upper gastrointestinal hemorrhage and is self-limiting in most cases. Several factors might contribute to increased mortality, a severe course of bleeding and recurrent bleeding, including advanced age, comorbidity, intestinal ischemia, bleeding as a result of a separate process, and hemodynamic instability. Diverticula, angiodysplasias, neoplasms, colitis, ischemia, anorectal disorders and postpolypectomy bleeding are the most common causes of LGIB. Volume resuscitation should take place concurrently upon initial patient assessment. Colonoscopy is the diagnostic and therapeutic procedure of choice, for acute and chronic bleeding. Angiography is used if colonoscopy fails or cannot be performed. The use of radioisotope scans is reserved for cases of unexplained intermittent bleeding, when other methods have failed to detect the source. Embolization or modern endoscopy techniques, such as injection therapy, thermocoagulation and mechanical devices, effectively promote hemostasis. Surgery is the final approach for severe bleeding.
Barnert, J. & Messmann, H. Nat. Rev. Gastroenterol. Hepatol. 6, 637646 (2009); doi:10.1038/nrgastro.2009.167

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Introduction

Learning objectives
Upon completion of this activity, participants should be able to: 1 Describe clinical features of lower gastrointestinal bleeding (LGIB). 2 Distinguish among different causes of acute LGIB and hematochezia. 3 Describe the diagnostic approach for angiodysplasia in patients with LGIB. 4 Identify the most common causes of anemia associated with chronic LGIB. 5 Describe effective treatment strategies for different types of LGIB.

Competing interests The authors, the Journal Editor N. Wood and the CME questions author D. Lie declare no competing interests.

Hemorrhage from the lower gastrointestinal tract accounts for about 20% of all cases of acute gastrointestinal bleeding.1 Lower gastrointestinal bleeding (LGIB) has traditionally been defined as an abnormal loss of blood beyond the ligament of Treitz. However, results from capsule and double-balloon endoscopy have revolutionized the management algorithm of small bowel bleeding, and it has been shown that bleeding from the small bowel represents a distinct entity.2 It therefore seems reasonable to divide gastrointestinal bleeding into three categories: upper, middle, and lower bleeding. In this article, we define LGIB as the acute or chronic loss of blood from a source in the colon or anorectum. Acute LGIB is defined as being of recent duration (arbitrarily designated as less than 3 days) and might result in instability of vital signs, anemia and/or the need for blood transfusion. Chronic LGIB is the passage of blood from the rectum over a period of several days or longer and usually implies that blood loss is intermittent or slow. A patient with chronic bleeding can show occult fecal blood, iron-deficiency anemia, occasional episodes of melena, hematochezia or maroon stools, or small quantities of visible blood per rectum.3 Alternatively, however, LGIB can be subdivided into two categories: clinically overt gastrointestinal bleeding (melena, hematochezia) or occult bleeding, identified by an unexplained iron deficiency and/or positive fecal occult blood testing result. The incidence of LGIB in the US ranges from 20.5 to 27 cases per 100,000 adults.4 In The Netherlands, an overall incidence of 8.9/100,000 per year has been

Department of Internal Medicine III, Klinikum Augsburg, Augsburg, Germany (J. Barnert, H. Messmann). Correspondence: H. Messmann, Klinikum Augsburg, Stenglinstrasse 2, D-86156 Augsburg, Germany helmut.messmann@ klinikum-augsburg.de

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Key points
The severity of acute lower gastrointestinal bleeding (LGIB) is variable, but overall mortality is low In most cases, bleeding will stop spontaneously Mortality is higher in older adults, and in those with intestinal ischemia and other comorbidities Colonoscopy is the diagnostic and therapeutic mainstay in the management of acute and chronic LGIB Visceral angiography is the preferred diagnostic and therapeutic method in patients with hemodynamic instability The existing scoring systems are time consuming and offer little help in clinical decision-making

reported.5 Differences in incidence might be explained by the different populations, use of medicine, endoscopic and pharmaceutical management, and different selection criteria. The age range of patients with LGIB is 6377 years;4 the incidence increases with age, with a >200-fold increase between 20 and 80 years. LGIB occurs more often in men than in women.6 Compared with acute upper gastrointestinal bleeding, patients with acute LGIB are significantly less likely to experience shock (19% versus 35%, respectively), require fewer blood transfusions (36% versus 64%) and have a significantly higher hemoglobin level (84% versus 61%).7,8 Colonic bleeding necessitates fewer blood transfusions compared with bleeding from the small intestine.8 Acute bleeding in the lower gastrointestinal tract stops spontaneously in the majority (8085%) of patients. The overall mortality rate ranges from 2% to 4%.4 In this Review, we aim to provide a critical overview of the existing published data concerning the evaluation and management of LGIB.

Initial evaluation and resuscitation

On presentation with LGIB, a number of factors relating to the patients history should be considered: intake of aspirin or NSAIDs, occurrence of vascular disease, past bleeding episodes, radiation therapy for prostatic or pelvic cancer, occurrence within the previous 2 weeks of colonoscopy or polypectomy, HIV infection, liver cirrhosis, IBD, coagulopathy (including anticoagulation therapy), and indication of colorectal cancer (family history, weight loss, changes in bowel habits). The duration of bleeding, frequency of bleeding episodes and stool color are of further importance. Hematochezia is indicated by bright red or maroon blood per rectum and must be differentiated from melena, the passage of tarry stool, the presence of which is suggestive of an upper gastrointestinal bleeding source (although bleeding from the cecum and right-sided colon occasionally present in this manner). Up to 11% of patients with hematochezia have massive upper gastrointestinal bleeding.9 Passage of bright red blood resulting from upper gastrointestinal bleeding is associated with hemodynamic instability (shock or orthostatic hypotension). The presence of blood in nasogastric tube aspirates is highly predictive

of bleeding proximal to the ligament of Treitz, but this source cannot be excluded if blood is absent from the aspirate. Careful digital rectal examination should be performed to exclude anorectal pathology and to confirm the patients description of stool color. Physical examination also helps to assess the severity of bleeding and to stratify patients according to the severity of hemorrhage. Blood loss of <200 ml has no effect on heart rate or blood pressure; however, loss of >800 ml causes a drop in blood pressure of 10 mmHg and an increase of 10 heartbeats/min. Extensive blood loss (>1500 ml) might induce shock. Other signs of hemodynamic compromise include postural changes, fatigue, pallor, palpitations, chest pain, dyspnea and tachypnea. The initial laboratory evaluation should contain a complete blood count, a coagulation profile, serum chemistry and a sample for blood type and crossmatch. Patients with clinical evidence of ongoing or aggressive bleeding, those with a transfusion requirement of greater than two units of packed red blood cells, and those with a significant morbidity should be monitored in an intensive care unit (ICU) setting. Conversely, a young, nonanemic patient with scant bleeding, who is otherwise healthy, can be managed as an outpatient. Coagulopathy (defined as an international normalized ratio of prothrombin time >1.5) or thrombocytopenia (<50,000 platelets/l) should be treated using fresh frozen plasma or platelets, respectively. In patients receiving warfarin, anticoagulation should be reversed with vitamin K, although the onset of action is delayed compared with the use of fresh frozen plasma or prothrombin complex. The ideal plasma substitute for volume replacement remains a matter of debate. In general, crystalloids (for example, lactated Ringers solution) are recommended for volume substitution in the US,10 whereas colloids, such as low and medium molecular weight hydroxyethylstarch preparations with low molar substitution, are considered to be more appropriate for treating intravascular volume deficits in Europe.11 If there is ongoing hemorrhage or severe anemia, red blood cells should be used. The ideal hemoglobin concentration/hematocrit depends on the patients age, rate of bleeding, and any comorbidities. A young and otherwise healthy person will tolerate a hemoglobin concentration of less than 78 g/dl (hematocrit <2025%), whereas older patients develop symptoms at this level. Maintaining the hemoglobin concentration around 10 g/dl (hemato crit 30%) in high-risk patients (for instance, an elderly patient with coronary heart disease) would be reasonable. However, it must be emphasized that all these recommendations have been given on an empirical basis.

Etiologies

The sources of acute LGIB and their frequency as reported in the literature are listed in Table 1. Colonic diverticula (Figure 1) seem to be the most frequent source of hematochezia, followed by angiodysplasias,

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IBD and postpolypectomy bleeding. The causes of chronic LGIB and their frequency are more difficult to determine, although they cause 1830% of irondeficiency anemia, the most common manifestation of chronic gastrointestinal bleeding (Table 2). Chronic intermittent passage of small amounts of visible red blood most often originates from anal lesions, such as hemorrhoids or anal fissures. Otherwise, bleeding lesions are usually located in the rectum or distal colon. In middle-aged and older indivi duals, further examination might be needed, even if an anal or rectal lesion seems to be responsible for bleeding, to exclude a coexisting colon neoplasm.
Table 1 | Sources of hematochezia reported in the literature (based on14) Source/finding
Diverticulum Angiodysplasia Colitis (ischemic, infectious, chronic IBD, radiation injury) Neoplasia, postpolypectomy bleeding Anorectal disease (including rectal varices) Upper gastrointestinal bleeding Small bowel bleeding

Frequency (%)
1740 921 230 1114 410 011 29

Diverticular disease Bleeding from colonic diverticula (Figure 1), which presents as acute, painless hematochezia, is arterial and can occur either at the dome or the neck of the diverticulum. The prevalence of colonic diverticula increases with age, affecting about two thirds of people over 80 years. Although these structures are reportedly the most frequent source of acute LGIB (Table 1), they are often cited as the source of bleeding in the colon for lack of evidence of another source. Colon diverticula were identified as the source in 22% of cases of acute LGIB, based on active bleeding or the presence of stigmata, such as a visible vessel or an adherent clot.12 The majority (>75%) of diverticula are found in the left colon. Using colonoscopy, 60% of cases of diverticular bleeding can be observed in the left colon.6 However, the bleeding diverticulum is localized more often in the right colon when using angiography for diagnosis.3,4 Bleeding ceases spontaneously in about 80% of cases. The cumulative risk of rebleeding for these patients is 25% after 4 years.6 Data on the recurrence rate of bleeding after endoscopic therapy are inconsistent: Jensen and colleagues12 observed no recurrence, whereas Bloomfeld and colleagues13 reported an early recurrence in 38% of patients. Angiodysplasia Angiodysplasias (also known as vascular ectasias or angioectasias) (Figure 2) are cited in up to 30% of cases as the source of acute LGIB (Table 1); a rate of 312% is probably more realistic. 14 Angiodysplasias are also said to be an important cause of chronic LGIB (Table 2). The majority of colonic angiodysplasias are located in the right hemicolon, often as multiple lesions; the number of lesions increases with age. Angiodysplasias are seldom found during routine colonoscopy (0.83%15 and 1.4%16). Most angiodysplasias do not bleed, 15,16 and so most patients are asymptomatic. Overt bleeding often occurs as a result of coagulopathy or platelet dysfunction, and NSAIDs, aspirin or anticoagulants might have a role in triggering bleeding.17 Angiodysplasias appear endoscopically as red, circumscribed mucosal lesions measuring from one millimeter to a few centimeters (Figure 2). As most do not bleed,18,19

Figure 1 | Bleeding from a small diverticulum, recognizable by a streak of red blood.

therapy is not always advocated. Furthermore, angiodysplasias seen during emergency colonoscopy should not automatically be identified as the bleeding source unless they are acutely bleeding or show stigmata (for example, a visible vessel, an adherent clot or submucosal bleeding). It is important to avoid the use of opiates and coldwater lavage of the mucosa during colonoscopy, because these substances reduce mucosal blood, decreasing diagnostic yield.2022 Chronic radiation proctopathy is a common complication of radiation therapy in the pelvic region that might cause rectal bleeding. The term proctitis is a misnomer, as there is no inflammation on biopsy; instead, radiationinduced endarteritis obliterans induces neovascularization. Multiple telangiectasias among a pale mucosa can be seen by endoscopy, which can lead to considerable and recurrent blood loss. Following radiation therapy for prostatic carcinoma, 413% of patients report rectal bleeding.23,24 In hereditary hemorrhagic telangiectasia (HHT; also known as OslerWeberRendu syndrome), bleeding occurs in one-third of patients.25 The most common localization of HHT is the stomach and the small bowel; the colon is less often affected.26 Patients over 60 years are particularly at risk, butunlike angiodysplasiasHHT affects younger people as well.

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Table 2 | Colonic causes of iron-deficiency anemia based on literature reports9094 Finding
Colon carcinoma Angiodysplasia Colon polyps Colitis Colonic causes in total

Frequency (%)
4.511 0.98.5 2.87.2 1.42 1830

Figure 2 | Angiodysplasia in the ascending colon, slightly elevated above the mucosa.

Mucosal inflammation Massive hemorrhaging leads to hospitalization in 0.1% of patients with ulcerative colitis and 1.2% of patients with Crohns disease.28 In half of the patients, bleeding stops spontaneously, but rebleeding occurs in 35% of these patients.29 In infectious colitis (including pseudomembranous colitis), life-threatening hemorrhage is rare. In patients with HIV, the most common causes of LGIB differ from those in other patients, and include cytomegalovirus colitis (25%), lymphoma (12%), and idiopathic (unidentifiable) colitis (12%).30 Colonic histoplasmosis, Kaposis sarcoma in the colon, and bacterial colitis are further sources of bleeding. Mortality related to bleeding in patients with HIV is around 14%.30 The use of NSAIDs is associated with an increased risk of gastrointestinal bleeding. Lanas et al.31 found a strikingly high prevalence (86%) of NSAID use (especially aspirin) in patients with LGIB. NSAIDs are also commonly used in patients with iron-deficiency anemia. Pre-existing lesions, such as diverticula, angiodysplasias, polyps, cancer and colitis, are prone to bleeding with NSAID use. Furthermore, NSAIDs can cause mucosal damage, colonic inflammation, erosions and ulcerations. NSAID use might also exacerbate underlying colitis. The mucosal aspect of NSAID-induced colopathy can resemble infectious colitis or chronic IBD, but the lesions often present themselves as flat and usually irregularly shaped erosions and ulcerations in a normal appearing mucosa. Neoplasia Carcinomas account for 29% of cases of hematochezia,32 and are by far the most frequent cause of iron-deficiency anemia and source of chronic LGIB (Table 2). Erosions and ulceration on the surface of the tumor might bleed, and bleeding is often exacerbated by the use of NSAIDs. Carcinoma in the left colon, especially in the sigmoid, often leads to rectal bleeding early in the course of the disease. In the right colon, by contrast, carcinoma often presents as iron-deficiency anemia. Colonic polyps are cited in 511% of patients as the source of acute LGIB,14 and in 37% as the cause of irondeficiency anemia (Table 2). Usually, only polyps larger than 1 cm bleed. Postpolypectomy bleeding Postpolypectomy bleeding is the most frequent complication of colonoscopy and is seen in 0.21.8% of cases of colonoscopic polypectomy.3341 This type of bleeding accounts for approximately 28% of cases of acute LGIB.4 Delayed bleeding might occur up to 14 days after polypectomy.35,36 Massive bleeding arising concomitant with the polypectomy procedure is typically arterial and results from inadequate hemostasis of the blood vessel in the polyp stalk. Kim and colleagues33 used multivariate analysis to assess polypectomy-induced immediate bleeding and identified several risk factors: size of the polyp, cutting mode of the electrosurgical current, incidence of inadvertent cutting of a polyp before current application,

Ischemic colitis The occurrence of hematochezia caused by colonic ischemia seems to increase in frequency in our clinical practice, most likely owing to an increase in frequency of aged patients with cardiovascular diseases. However, there are no reliable data available on the incidence of nonocclusive ischemia of the colon. The cause of ischemic colitis is a sudden, often temporary, reduction in mesenteric blood flow resulting from episodes of low blood pressure or vasospasm. Typically, the watershed areas of the colonthe splenic flexure and rectosigmoid junctionare affected. Colonic ischemia mostly affects older persons with advanced athero sclerosis and/or cardiac disease, although vasculitis might be a rare cause. A specific precipitating event can almost never be identified. Patients experience a sudden onset of mild abdominal pain, usually followed by hematochezia or bloody diarrhea. Bleeding is self-limiting in almost all cases; but colonic ischemia is associated with an increased risk of mortality. 27 By endoscopy, submucosal hemorrhage and mucosal nodularity are present during the early stages or, alternatively, a livid or pale, nonedematous mucosa can be seen. In the later stages, when blood and edema have been reabsorbed, the endoscopic appearance is less characteristic. The mucosa might be red, the vessel pattern might be obscured, and ulcerations can appear.

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gross morphology of the polyp (pedunculated or laterally spreading), comorbidity (cardiovascular and renal disease), bowel preparation, age (>65 years) and experience of the endoscopist. They also found out that even a mild degree of immediate bleeding during polypectomy was significantly associated with the development of delayed bleeding. Three groups35,36,41 looked for factors increasing the risk of delayed postpolypectomy bleeding. All identified polyp size as a risk factor. The Munich study group41 noted that polyp location in the right colon was a further risk factor. Watabe et al.36 identified hypertension as an additional risk factor, but this condition was not confirmed by Sawhney and colleagues.35 The latter group reported that the resumption of anticoagulation therapy within 1 week of polypectomy increased the risk of severe, delayed, postpolypectomy bleeding. By contrast, the continued use of aspirin or NSAIDs was not associated with an increase in postpolypectomy bleeding.42 Only a few patients in this study used newer antiplatelet agents like clopidogrel and ticlopidine or COX II inhibitors. None of these patients developed postpolypectomy bleeding, but the small number of patients does not enable a clear conclusion to be drawn.
Hematochezia No Hemodynamically stable? Yes

Stabilization of the patient Not possible Possible EGD Yes Bleeding site localized No Bleeding site localized Endoscopic therapy Unsuccessful

Colonoscopy

Negative

EGD without localizing bleeding site

Severe hemorrhage no potential to localize bleeding site

Endoscopic therapy

Angiography +/ embolization Surgery

Capsule endoscopy and/or double-balloon enteroscopy

Anorectal diseases Hemorrhoids are the source of acute LGIB in 29% of patients (for an overview, see reference14). Acute LGIB from anal fissures is rare. Fissures are relatively easily diagnosed by inspecting the anus. The patient typically has severe pain upon spreading the anus, but the lesion can be carefully and painlessly inspected after injecting a local anesthetic. Bleeding from fissures usually ceases spontaneously. Local ischemia seems to be important in the pathogenesis of solitary rectal ulcer. Internal rectal prolapse or lack of inhibition of the puborectalis muscle during straining have been implicated as causal factors. Heavy bleeding is rare. Bleeding from rectal varices can be seen in patients with portal hypertension. Rectal varices have a grayblue color and might be confounded by mucosal folds. Bleeding is usually severe. The incidence of bleeding from rectal varices is reported to be 18%.43 Chronic intermittent passage of small amounts of visible red blood indicates in most patients a bleeding source that is in the anus, rectum or sigmoid. Hemorrhoids and chronic anal fissures are the most common bleeding source in young (<40 years) patients with chronic LGIB. In patients over 50 years of age colorectal neoplasia must be excluded by colonoscopy or CT colonography. This approach is valid even if a benign (potential) anorectal source of bleeding is present, such as hemorrhoids or an anal fissure. In patients with radiation history, chronic radiation proctopathy must be considered as a potential cause of chronic scant bleeding. Dieulafoys lesion Dieulafoys lesion is a rare source of acute colonic bleeding. It is caused by an exposed artery that arises within

Figure 3 | Algorithm showing recommended evaluation of acute lower gastrointestinal bleeding from initial presentation of the patient with hematochezia. Stabilization of the patient should be carried out before colonoscopy is performed. If this is not possible, angiography should be performed first. In other cases, colonoscopy is the mainstay in the diagnostic algorithm. Abbreviation: EGD, esophagogastroduodenoscopy.

a minute mucosal defect and, unless bleeding is visible, might be difficult to detect.

Detection of LGIB

Our recommended approach to patients with acute LGIB is summarized in Figure 3. For chronic LGIB, colonoscopy and anoscopy are the cornerstones for investigation. If repeat colonoscopies and upper endoscopies are negative, the small bowel must be investigated as a potential source of the bleeding.

Endoscopy Flexible endoscopy is now considered the mainstay for evaluation of acute and chronic colonic bleeding. The incidence of serious complications is low (about 1 in 1,000 procedures). Patients should be continuously monitored during urgent endoscopy using ECG and noninvasive measurement of oxygen saturation. In case of hemodynamic instability, patients must undergo volume resuscitation before endoscopy. In patients with hematochezia and concurrent hemodynamic instability, esophagogastroduodenoscopy (EGD) should be performed first to exclude an upper gastrointestinal bleeding source. Otherwise, colonoscopy is recommended as the first step in the evaluation of acute LGIB.44 The timing of colonoscopy after initial presentation varies among studies from 12 h to 48 h.44 Colonoscopy can determine the source and type of bleeding, and can help to identify patients with ongoing hemorrhage or those who are at high risk of rebleeding. Furthermore, endoscopic hemostasis can be performed, if necessary.

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The diagnostic yield for urgent colonoscopy in acute LGIB is 8997%.45,46 Current recommendations advise thorough cleansing of the colon in acute LGIB,3,47 as this procedure facilitates endoscopic visualization, improves diagnostic yield, and improves (presumably) the safety of the procedure by decreasing the risk of perforation. For optimal purge of the colon, the patient must consume 36 l of a polyethylene glycol-based solution. Patients generally tolerate consumption of 12 l per hour. It might be helpful to administer a prokinetic antiemetic such as metoclopramide (10 mg intravenously) or to administer the solution through a nasogastric tube. Colonoscopy can be started with the appearance of liquid discharge because diluted blood and clots can be aspirated or washed away. If the discharge becomes free of blood during the preparation, the endoscopic evaluation can be done on an elective basis the following day. The cecum should be reached if at all possible, because a substantial proportion of bleeding sites are located in the right hemicolon. Flowing blood from above in the terminal ileum is a clear sign of a proximal bleeding site. In patients with severe and ongoing bleeding, urgent colonoscopy must sometimes be carried out without purge. In patients with hemodynamic instability, an urgent angiography is recommended. For chronic LGIB, colonoscopy and anoscopy should be performed first in patients with scant intermittent hematochezia or iron-deficiency anemia. EGD should be carried out in patients with iron-deficiency anemia if colonoscopy fails to detect the source of bleeding. If both colonoscopy and EGD fail to localize the source in acute and chronic GI bleeding, additional endoscopic methods can be performed to examine the small intestine. Push enteroscopy enables visualization of about 50120 cm of the proximal jejunum. Double-balloon enteroscopy can make the whole small intestine visible, especially if bidirectional enteroscopy is performedthat is, if the scope is introduced successively by mouth and anus. Using wireless video capsule endoscopy, the small bowel can be completely visualized in about 80% of cases.48
Radiology Visceral angiography is estimated to only detect active bleeding when the rate is at least 0.51 ml/min.50,51 The specificity of this procedure is 100%, but sensitivity varies from 47% with acute LGIB to 30% with recurrent bleeding.52 Unfortunately, bleeding is frequently intermittent and might be slow, thereby limiting detection of the causative lesion. Angiography should be reserved for patients who have massive bleeding that precludes colonoscopy, or for whom endoscopies were negative. Visceral angiography has a complication rate of 9.3%. 53 Studies have shown that CT angiography is highly sensitive and specific for diagnosing colonic angiodysplasia.54,55 This approach seems to be equivalent to visceral angiography in the detection of acute gastrointestinal hemorrhage,56 showing accuracy rates of 5479% for colonic bleeding.57,58 There is no role for barium studies in the detection of acute LGIB. Plain abdominal radiography and/or CT might be carried out, depending on the clinical presentation and suspected etiology (such as ischemic or inflammatory colitis, or in cases where bowel obstruction or perforation are suspected). In cases of chronic LGIB, CT colonography can be used to examine the colon. However, it must be considered that small or flat lesions such as angiodysplasias are usually not recognized by this method.

Therapy
Endoscopic hemostasis Endoscopic treatment modalities for LGIB include injection, contact and noncontact thermal coagulation, and mechanical devices such as metallic clips and band ligation. The use of these techniques depends on the site and the features of the bleeding lesion, the clinicians personal experience with the devices, and access to the bleeding site. Randomized studies on the management of specific lesions are rare; most reports are case histories (Table 3).
Thermal coagulation Thermal coagulation is one of several hemostatic techniques. In bipolar (BICAP) and monopolar electrocoagulation, an electrical current from a probe heats up the tissue, whereas a heater probe directly delivers heat. All three probes induce coagulation upon contact. Perforation in the thin-walled right hemicolon occurs in up to 2.5% of patients undergoing thermal coagulation.19 The BICAP probe shows an increase in energy deposition when greater pressure is applied, or when increased angulation causes an increase in tissue contact. For the heater probe, which has a non-stick Teflon coating, these associations have not been observed.59 BICAP and heater probe enable water jet irrigation through an opening on the probe tip. Argon plasma coagulation (APC) transmits energy to the tissue without contact by means of ionized argon gas. The penetration depth is limited by the extent of tissue desiccation, whereas the coagulation depth depends on the power setting, duration of application, and distance from the probe tip to the target tissue.60 The risk

Nonendoscopic methods
Nuclear scintigraphy Nuclear scintigraphy is a sensitive method for detecting gastrointestinal bleeding at a rate of 0.1 ml/min. The method is more sensitive, but less specific, than angiography.49 The role of nuclear scans and, in particular, of technetium-99m-labeled erythrocytes is limited for obscure gastrointestinal bleeding. The major disadvantages are that nuclear imaging localizes bleeding only to an area of the abdomen and that the intraluminal blood is moved away by intestinal motility. When scans are positive within 2 h after injection of the labeled erythrocytes, localization is correct in 95100% of cases. However, when scans are positive after more than 2 h after injection, the accuracy decreases to 5767%. 8 Scintigraphy might be useful, especially for recurrent bleeding, when other methods have failed.

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Table 3 | Endoscopic management of specific lesions: a summary of case studies Method
BICAP Heater Laser Argon plasma coagulation Epinephrine injection Sclerosant injection Acryl glue injection Clip Rubber band Cryotherapy Infrared coagulation Low voltage current

Diverticulum
++12,13 + ++ ++12,13 ++; P +85

Angiodysplasia
++86 ++
86

Dieulafoy
++ ++ +

Neoplasia
+ + ++ ++; P + ++88 +

Postpolypectomy
+ + + ++14 + ++14,87; P

Colitis
+28 + + ++28 +89 ++90; P

NSAID
+ + + ++ ++; P

Hemorrhoids
++91 ++ + ++92 ++ ++92 +
93 91,94

Rectal varices
+ ++; P + +

+32 ++; P + + +
87

++; P +91 + ++91 +

+92,94 +84,93,94

Abbreviations: +, can be done; ++, recommended; , not recommended; P , personal preference of the authors.

of perforation in the colon seems to be almost nonexistent.17 Probes that direct the plasma stream parallel or perpendicular to the axis of the catheter are available. In laser-mediated coagulation, the high-energy laser light causes vaporization of the tissue. The deep penetration of a laser pulse (especially by Nd:YAG laser) increases the perforation risk.
Injection therapy Injection therapy is an inexpensive and straightforward method. Epinephrine (at a 1:10,000 dilution) is usually used, causing vasoconstriction and physical compression of the vessel. Addition of a sclerosant (for example, ethanolamine) seems to confer no additional advantage. In bleeding rectal varices, a cyanoacrylate glue is injected to repair the lesion.

carefully monitored owing to the danger of full-thickness tissue entrapment and the subsequently increased risk of perforation.

Mechanical devices Metallic clips can be used to definitively and securely close bleeding lesions. Both reusable and single-use clipping devices are available. The reusable device, manufactured by Olympus (Olympus America Inc., Center Valley, PA), is less costly and available in different sizes, but requires a skilled assistant for loading and handling; after several uses, the rotation capability of the device becomes erratic. Singleuse pre-loaded clipping devices, such as the QuickClip2 (Boston Scientific, Natick, MA) are easy and quick to use. Ligation with rubber bands is used for bleeding hemorrhoids and bleeding rectal varices and, in certain circumstances, for treatment of focal lesions that are <2 cm in diameter in nonfibrotic tissue, The technology and equipment used for the treatment of esophageal varices must be used in this setting. The amount of tissue suctioned into the cap before application of the rubber band must be

Interventional angiography Transcatheter embolization is an effective method of controlling gastrointestinal hemorrhage. Embolization proximal to the mesenteric border of the colon was initially carried out via large catheters (5 French), which led to a significant rate of bowel infarction (1333%).4 However, the availability of microcatheters (2.7 French) and embolization methods such as microcoils, gelfoam, and polyvinyl alcohol particles renewed enthusiasm for this technique. Success rates range from 70% to 90% without major ischemic complications;4 recurrent hemorrhage occurs in less than 15% of cases.61 The location and etiology of bleeding have important therapeutic implications for angiotherapy. Bleeding from the right colon and cecum might be less amenable to embolization than bleeding in the left colon. Angiodysplasias are more difficult to treat using embolization compared to diverticular bleeding, and have a greater tendency (740%) to rebleed. 62,63 Angiography and embolization should be reserved for those patients who have massive bleeding with hemodynamic instability that precludes urgent colonoscopy, or for whom colonoscopy has failed to identify a bleeding source. Intra-arterial infusion of vasopressin or its longer acting analog, terlipressin, is successful in controlling gastrointestinal hemorrhage, but rebleeding occurs in up to 50% of patients after cessation of the infusion.64 Vasopressin and terlipressin also cause significant adverse effects, including abdominal pain, and are contraindicated in patients with coronary heart disease. This technique is now used only in exceptional cases.

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Surgery Most patients with LGIB will not require surgery, although this is the therapy of choice in patients with bleeding related to neoplasia. Surgery should also be considered in patients for whom a bleeding source has clearly been identified and conservative therapies have failed. In fulminant bleeding or in patients with recurrent bleeding without localization of the bleeding source, surgery is the last resort. Blind segmental colectomy is associated with unacceptably high rates of morbidity (rebleeding rate as high as 75%) and mortality (up to 50% of patients who have undergone surgery) and should therefore be avoided at all costs. Whenever possible, intraoperative endoscopy should be carried out in such patients to clearly localize the bleeding source. Directed segmental resection is the treatment of choice because of its low morbidity, mortality (about 4%) and rebleeding rate (about 6%).65 Pharmacotherapy Hormonal therapy of angiodysplasia using estrogen and progestagen has not been successful. Somatostatin and its analog, octreotide, have been reported to reduce blood loss from intestinal angiodysplasias.66,67 Octreotide was also successful in a patient with bleeding from portal colopathy.68 In angiodysplasias, antagonists of vascular endothelial growth factor, such as thalidomide, seem to show reasonable efficacy. One study showed that thalidomide prevented rebleeding in patients with angiodysplasias and in patients with severe bleeding related to Crohns disease.69 However, the use of thalidomide is associated with severe adverse effects and teratogenicity.
unnecessary ICU admissions and the frequency of urgent interventions. Kollef and colleagues74,75 have identified several risk factors for predicting adverse outcomes of both acute upper GI bleeding and LGIB: ongoing bleeding, low systolic blood pressure, elevated prothrombin time, erratic mental status, and the presence of an unstable comorbid disease. Although high-risk and low-risk patients were defined using these criteria, this BLEED classification has not been widely adopted clinically. Strate et al.76 identified several predictors for severe course and bleeding recurrence in acute LGIB. These predictors include a heart rate of 100/min, systolic pressure 115 mmHg, syncope, nontender abdominal examination, bleeding per rectum during the first 4 h of evaluation, a history of aspirin use and the presence of more than two active comorbidities. Using these criteria, patients were stratified into three risk groups: low (no risk factor), moderate (13 risk factors), and high (>3 risk factors). The magnitude of the risk score was significantly correlated with major clinical outcomes including surgery, death, blood transfusions, and length of hospitalization.77 The same group27 has published another study using multivariate analysis to identify variables in acute LGIB that are associated with mortality. These variables include age (patients above 70 years versus patients aged below 50 years), the occurrence of intestinal ischemia, two or more comorbidities, bleeding while hospitalized for a separate process, a coagulation defect (or chronic anticoagulant usage), hypovolemia, transfusion of packed red cells and sex (male). Among these variables, advanced age, intestinal ischemia and comorbid illness were the strongest predictors of mortality, whereas the presence of colorectal polyps and hemorrhoids was associated with a lower risk of mortality. The all-cause in-hospital mortality rate of LGIB reported in this study was 3.9%. Das and colleagues78 used a model based on an artificial neural network to predict clinical outcome in LGIB and compared it to a multiple logistic regression model and the BLEED classification. 75 Using a commercial neural network computer program and 19 clinical measures as input variables, they could predict mortality, recurrent bleeding and need for intervention with a high degree of accuracy. Patients at low risk of adverse outcomes, in particular, could be accurately identified by this method. Moreover, the positive predictive value for death was low. The predictive accuracy of the artificial neural network was similar to the multiple logistic regression model and was superior to the BLEED classification.75

Clinical outcome and recurrence

Patients with chronic LGIB presenting as chronic iron deficiency anemia or positive occult blood in stool require colonoscopy because examination of the entire colon has been demonstrated to significantly reduce the rate of mortality from colon cancer. For acute LGIB, two studies demonstrated that early colonoscopy is significantly associated with a shorter hospital stay.70,71 By contrast, another study found that early colonoscopy is not superior to a standard care algorithm.72 One benefit of urgent colonoscopy is endoscopic risk stratification. Jensen et al.12 and Grisolano et al.73 have shown that evidence of active bleeding, visible vessels and adherent clots are associated with a severe course of diverticular bleeding and a high rate of rebleeding, but this result was contradicted by another study.13 In general, diverticular bleeding is characterized by a high rate of spontaneous cessation of bleeding and a considerable risk of rebleeding in the long term.6 A reliably predictive model that can accurately forecast the outcome of an episode of acute LGIB in terms of risk of recurrent bleeding, need for therapeutic intervention, and more importantly, the risk of mortality, would be extremely useful for triage of patients in order to assure appropriate and cost-effective levels of care. This approach would consequently improve medical resource utilization by reducing

Conclusion

Although not as common as, and less fatal than, upper gastrointestinal bleeding, LGIB occurs increasingly with advancing age and is associated with substantial morbidity and mortality. Advances especially in endoscopic and angiographic intervention approaches have improved therapy for LGIB and, subsequently, patient outcome, although the benefits are limited by the increasing age of

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the patients and their frequent comorbidities. There are several risk scores to stratify patients with acute LGIB to appropriate levels of care and intervention. These scores can be helpful in clinical decision-making, but none comes close to being an ideal risk score. Good prospective clinical studies are still rare and often include only a few patients. Treatment decisions are therefore usually based on personal expertise and preference. Some publications indicate that urgent endoscopy will have a similar role in LGIB as it currently does for upper gastrointestinal bleeding, but further studies are needed to clarify this issue.
Review criteria
A MEDLINE search was performed for English-language papers published between 1966 and June 2009 using the terms gastrointestinal hemorrhage, gastrointestinal bleeding, occult gastrointestinal bleeding, and colonoscopy. Reference lists from relevant publications were also analyzed to identify additional applicable publications not found by the database searches. If deemed appropriate, abstracts from the Digestive Disease Week (DDW) conferences from the past 4 years were also used.

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