Gastroenterology Hepatology

GI Bleeding

How can I be sure that a patient has gastrointestinal bleeding?

Gastrointestinal (GI) bleeding can range from trivial bleeding to massive and life-threatening blood loss. Although it can be easy to diagnose by clinical history, it can also present a diagnostic challenge in the absence of clear blood loss in the stool. Because of this, GI bleeding is often classified into overt GI bleeding with visible blood in emesis or stool, or as occult GI bleeding wherein there is no visible blood but laboratory evidence of either iron deficiency anemia or blood in the stool.

The term obscure GI bleeding refers to bleeding that persists or recurs with no identifiable origin after endoscopic evaluation. It can entail both overt and occult bleeding.

Diagnosis often requires endoscopic evaluation, either by upper endoscopy, colonoscopy, enteroscopy or capsule endoscopy.

What are the causes of GI Bleeding?

Causes of GI bleeding can be divided into two categories based on the location in relationship to the ligament of Treitz: upper GI bleeding (UGIB) originates proximal to the ligament of Treitz, whereas lower GI bleeding (LGIB) occurs distal to it.

Causes of Upper GIB

Esophagitis: inflammation of the esophagus rarely leads to severe bleeding. Causes of esophagitis include gastric reflux, pill-induced, radiation, and infections such as cytomegalovirus and herpes simplex virus.

Variceal bleeding: this occurs in the setting of portal hypertension and can originate from esophageal or gastric varices. This is most often seen in the setting of cirrhosis and can result in massive GI bleeding.

Mallory-Weiss tear: mucosal disruption occurring at the gastroesophageal junction which is classically a result of frequent retching and vomiting. This usually heals within a few days, although ongoing vomiting can lead to esophageal rupture (Boerhaave's syndrome).

Peptic ulcer disease: Peptic ulcer disease (PUD) occurs when ulcerations develop in the mucosa of the stomach or duodenum. It is the most common cause of acute UGIB and accounts for approximately 50% of cases. Risk factors include the use of non-steroidal anti-inflammatory medications including aspirin, Helicobacter pylori infection, and acid hypersecretion, such as in Zollinger-Ellison syndrome. Risk factors for ulcer hemorrhage include older age (age 65 and over), use of NSAIDs (dose-dependent), and a prior history of peptic ulcer bleed. Studies have shown that the endoscopic appearance of ulcers is strongly associated with rebleeding, need for surgery, and mortality.

Erosive and hemorrhagic gastropathy: gastric erosions are defined as 3-5 mm breaks in the mucosa that do not penetrate into the muscularis mucosa.

Stress ulcers: these occur in the setting of severe illness and physiologic stress and are thought to be related to splanchnic vasoconstriction that occurs during stress, leading to gastric hypoperfusion. The rates of stress ulcer bleeding are much lower than in the past, given ongoing improved ICU care and prophylaxis.

Portal hypertensive gastropathy: this entity occurs in the setting of portal hypertension and is characterized by congestion of the gastric mucosa from dilated arterioles and venules. The endoscopic appearance is often described as a "mosaic" or "snake-skin" pattern. This often leads to chronic occult blood loss and iron deficiency anemia.

Dieulafoy's lesion: an aberrant vessel protruding through the mucosa without an associated ulceration or mucosal abnormality. It can lead to intermittent, painless bleeding and is often difficult to identify endoscopically. With proper identification, endoscopic therapy is ultimately effective.

Vascular lesions: these include arteriovenous malformations, as well as diffuse linear vascular ectasia known as gastric antral vascular ectasia (or "watermelon stomach"), and Cameron's lesions.

Malignancy: both benign and malignant tumors in the upper GI tract can lead to bleeding.

Aortoenteric fistulas: a rare cause of GI bleeding that can be life-threatening. This occurs as a late complication after aortic graft surgery. It typically involves the distal duodenum and is difficult to diagnose.

Causes of Lower GIB

Diverticular bleeding: this occurs when diverticula form at sites of weakness in the wall of the colon, where arteries that penetrate the muscularis layer reach the mucosa. It is the most common cause of major LGIB in the United States, related to the high prevalence of diverticulosis in the population. Repeat endoscopy, angiography, and/or surgery may be needed with recurrent bleeding.

Anorectal disease: this includes hemorrhoids and anal fissures and is the most common cause of LGIB in ambulatory outpatient adults. GI bleeding from anorectal disease is classically described as bright red blood on the toilet tissue and around the stools, but not mixed in. It is often self limiting but can lead to severe hematochezia. Medical therapies include fiber supplementation, stool softeners, rectal suppositories, and sitz baths. Surgery and endoscopic therapy can be considered in those with severe bleeding and those who fail medical therapy.

Ischemic colitis: this occurs in the setting of "low flow state" and commonly involves the splenic flexure, descending colon, and sigmoid colon. This occurs most frequently in the elderly, with risk factors including cardiac disease, sepsis, recent major surgery, diabetes, chronic renal failure, and certain medications. Colonoscopy is a sensitive and specific diagnostic modality and is often needed for accurate diagnosis. Most cases are self-limited and improve with supportive medical treatment, although some cases can require surgery. Right-sided ischemic colitis is associated with a higher mortality.

Infectious colitis: multiple pathogens can cause bloody diarrhea, namely Shigella species, Campylobacter jejuni, invasive Escerichia coli or E. coli 0157:H7, and rarely Clostridium difficile, in addition to cytomegalovirus in immunocompromised individuals.

Radiation-induced proctopathy and colopathy: this entity can occur immediately after or several years after undergoing radiation therapy.

Malignancy: colonic tumors can present with overt bleeding if the malignancy ulcerates into underlying vessels. Endoscopic therapy can produce temporary hemostasis, although surgical resection is often the best long-term option.

Colonic angiodysplasia: this most often occurs in the right colon and usually involves multiple angiodysplasia. Bleeding is usually intermittent, mild, and self-limited. Treatment includes endoscopic management.

Inflammatory bowel disease: usually presents with small-to-moderate degrees of bleeding, with blood usually mixed within the stools.

Meckel's diverticulum: this is the most frequent congenital anomaly of the intestinal tract, with an incidence between 0.3-3.0% on autopsy reports. This resultant ileal diverticulum is a less common cause of bleeding, but can present with painless bleeding that may be melenic or bright red. Diagnosis can be made with a radiolabeled technetium scanning. Surgical excision is the treatment of choice.

Intussusception: this occurs when bowel "telescopes" on itself. It occurs uncommonly in adults. When it does, it is usually the result of a polyp or malignancy. Patients classically describe bloody stools mixed with mucus as "currant jelly." Treatment is usually surgical.

How can I confirm the diagnosis?

Overt GI bleeding is most often diagnosed clinically based on history and digital rectal examination. Occult GI bleeding is often suspected based on evidence of iron deficiency anemia or by fecal occult blood tests, including guaiac (hemoccult) test and immunochemical tests assessing antibodies against human hemoglobin.

Endoscopic evaluation is most often used to establish a specific diagnosis.

What other conditions should I look for in patients with suspected GI bleeding?

In cases without obvious GI bleeding, it is important to consider other causes of anemia, including menorrhagia, gross hematuria, retroperitoneal bleeding, hematoma formation, and hemolysis.

What is the right therapy for the patient with GI bleeding?

The right therapy for a patient with GI bleeding depends on the specific etiology. It often requires a combination of medical management and endoscopic interventions, although angiography and surgery may be needed.

What is the most effective initial therapy?

Initial management for patients with overt GI bleeding should aim to ensure adequate resuscitation, reverse coagulopathy, and initiate pharmacologic therapy if necessary. This can be followed by endoscopic evaluation for diagnosis and more definitive therapy.

Initial resuscitation focuses on restoring intravascular volume. Hospitalized patients should have two large-bore (18-gauge or larger) intravenous (IV) lines in place at all times. Patients should be typed and crossed in case blood products are needed, although O-negative units can be given without delay if necessary. IV fluid resuscitation should include isotonic fluids, either normal saline or lactated Ringer's solution. Packed red blood cells may be required in severe GI hemorrhage, with a goal of maintaining a hemoglobin above 7 g/dL in most hospitalized patients, with higher goals in the setting of coronary artery disease. A goal of approximately 8 g/dL is recommended in patients with suspected variceal bleeding, although overtransfusion should be avoided.

In the setting of acute GI bleeding with ongoing blood loss, coagulopathy should be reversed. For patients on chronic warfarin therapy, consider giving fresh frozen plasma and vitamin K. For those on heparin, protamine can be used for reversal. Novel oral anticoagulant agents such as dabigatran, apixaban, and rivaroxaban require special considerations regarding their half-lives and the timing of the last dose ingested. Ensure adequate renal perfusion to aid in clearance of these medications, as renal hypoperfusion can significantly prolong their half-life. Reversal agents, such as idarucizumab (Praxbind, an agent that binds dabigatran), are being increasingly studied and evaluated by the FDA

Multiple medications require important considerations in the setting of acute GI bleeding.Proton pump inhibitors (PPIs) inhibit the proton pump of the parietal cell (H+/K+-ATPase), allowing for an increase in the intragastric pH which in turn improves the coagulation process. The current standard of care for patients with suspected acute upper GI bleeding is to administer IV PPI therapy, either as intermittent boluses or as an infusion for the first 48-72 hours. High-dose oral PPI therapy (double-dose BID) can be given if IV PPI therapy is unavailable or if clinically active bleeding has stopped. IV histamine-2 receptor antagonists have not been shown to reduce surgery requirements or mortality rates in actively bleeding patients, and their use is not recommended.

For variceal bleeding, additional medications that should be given include vasoconstrictor therapy (e.g. octreotide) and antibiotic prophylaxis. Several vasoconstrictor agents produce splanchnic vasoconstriction and decrease portal blood inflow, including octreotide, vasopressin, somatostatin, and terlipressin. Because of its favorable side effect profile, octreotide is considered the agent of choice in the United States, with a recommended dose of 50 mcg IV bolus followed by a continuous infusion of 50 mcg/hour for 3-5 days. In addition, antibiotic prophylaxis is recommended for all patients with variceal hemorrhage; it has been shown to prevent the development of both spontaneous bacterial peritonitis and all-cause infection. Standard regimens include ciprofloxacin, norfloxacin or ceftriaxone, and should be given for 3-7 days duration.

Giving prokinetic agents, including erythromycin and metoclopramide, immediately before EGD has been shown to significantly reduce the need for repeat endoscopy and is considered cost-effective. These agents promote gastric emptying and can improve visualization.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

After initial resuscitation and management, endoscopic evaluation is often required as a next step in evaluation for both occult and overt GI bleeding.

Diagnostic and possible therapeutic modalities include the following

Esophagogastroduodenoscopy (EGD): This diagnostic and therapeutic modality allows direct visualization of the mucosa of the upper GI tract and is the preferred initial method for evaluating patients with UGIB. For acute GI bleeding, this should be performed within 24 hours of presentation and after the patient is clinically stable. Common therapies used in the management of UGIB include injection therapy (with dilute epinephrine, saline, or sclerosants), ablative therapy (with either thermocoagulation, electrocoagulation, or argon plasma coagulation), and mechanical therapy (with hemoclips and band ligation). In occult GI bleeding, EGD serves primarily as a diagnostic modality but can allow for therapeutic interventions such as in the setting of arteriovascular malformations.

Colonoscopy: this diagnostic and therapeutic modality allows direct visualization of the mucosa of the colon and is the most frequently used diagnostic tool for evaluating patients with LGIB. For this to be performed in an optimal fashion, patients must be adequately resuscitated and hemodynamically stable (in the setting of acute bleeding) and must undergo adequate bowel preparation to ensure that they are free of stool and debris. In the hospitalized patient with acute GI bleeding, current data suggests that urgent colonoscopy does not improve outcomes or lower hospital costs compared with routine elective colonoscopy. In the severe hematochezia, urgent endoscopic evaluation can be considered, with either rapid colon preparation (often requiring nasogastric tube placement) or tap water enemas which would allow for evaluation of the rectosigmoid colon and anal canal. The endoscopist can classify a lesion as a presumptive cause of bleeding if stigmata of recent hemorrhage is evident, including a non-bleeding visible vessel, an adherent clot, or fresh blood in the location.

Capsule endoscopy: this diagnostic modality entails the patient ingesting a small camera that enables visualization of the entire small bowel. The ingested camera then sends images to a recorder worn on the patient's belt as the camera is advanced by normal intestinal peristalsis. While it is virtually noninvasive, complications can include retention and bowel obstruction, both of which could necessitate further endoscopic or surgical need. This modality has become standard in recent years, especially in obscure GI bleeding.

Tagged red blood cell scan: this diagnostic imaging modality can be used as a bedside evaluation of active GI bleeding. While this procedure has a very low risk, the bleeding rate must exceed a rate of 0.1 mL/minute to detect GI bleeding. This test is positive in less than 50% of patients. It is particularly useful as a screening test before angiography, as patients with negative tagged RBC scans are unlikely to have a positive angiogram.

Angiography: this diagnostic and therapeutic modality, commonly performed by interventional radiologists, allows for accurate diagnosis and therapy in a rapidly bleeding patient. Bleeding rates generally must exceed 0.5 mL/minute. If the bleeding source is identified, selective embolization can be used to stop the bleed using either vasoactive drugs or embolic material such as tissue adhesives, occlusion devices, or embolic material. This modality is generally reserved for patients with suspected massive small bowel bleeding, with massive ongoing lower GI bleeding when a colonoscopy is not feasible, and with upper GI bleeding in which endoscopy either fails or is unable to localize the bleed.

Enteroscopy: this diagnostic and therapeutic modality allows direct visual examination of portions of the small bowel using a longer endoscope. Multiple different modalities and enteroscopes exist and are largely dependent on the local availability of each institution. A push enteroscopy involves use of a longer endoscope that is advanced into the small bowel, allowing for visualization of up to 50 cm of small bowel beyond the ligament of Treitz. Deep enteroscopy can be performed using single-balloon enteroscopy (SBE) and double-balloon enteroscopy (DBE), two techniques that use a modified enteroscope with one or two balloons attached at the distal end; the balloon system then serves as an anchor that can grip the intestinal wall and allow further advancement. Alternatively, spiral enteroscopy is used at some centers. Both SBE and DBE can be performed antegrade (oral insertion) or retrograde (anal insertion) to allow for evaluation of the entire small bowel.

Diagnostic and therapeutic algorithms for evaluating patients with GI bleeding

The decision to evaluate and manage patients with GI bleeding depends on the rate of bleeding, as well as the likelihood that the bleed is an upper vs lower GI etiology. For acute and overt GI bleeding felt secondary to an upper GI etiology, management should include initial resuscitation, reversal of coagulopathy, and initiation of pharmacologic agents. This should be followed by an EGD once the patient is clinically stable. For patients presenting with a suspected lower GI bleed, evaluation should consider the possibility of an upper GI source, with a reasonable diagnostic approach as documented in Figure 1. Patients with obscure GI bleeding despite EGD and colonoscopy should undergo considerations for a repeat EGD and/or colonoscopy versus evaluation with capsule endoscopy or, if bleeding fast enough, with a tagged RBC scan +/- angiography.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

In acute GI bleeding, surgery serves as a salvage therapy for the small group of patients in whom bleeding cannot be controlled by endoscopic therapy or angiotherapy. When required, surgery should not be postponed excessively in those patients with hemodynamic instability. The choice of operation is dependent upon the underlying cause of bleeding, the surgeon's experience, and the overall condition of the patient.

In cases of persistent chronic blood loss from numerous angiodysplasia of the intestine, endoscopic ablation may not be feasible. These patients may require plans for aggressive iron repletion, and may be considered for pharmacologic therapies including estrogen and octreotide.

How should I monitor the patient with GI bleeding?

Follow up for patients admitted with GI bleeding must be individualized to the patient and depend on a variety of factors, including the risk of rebleeding and the need for ongoing medical management.

After an initial bleed from a peptic ulcer is treated endoscopically, medical management with PPIs is recommended for 6-8 weeks. Patients who test positive for H. Pylori should receive eradication therapy with considerations for retesting after completion of antibiotics. Patients requiring long-term aspirin or NSAIDs should receive PPI maintenance therapy indefinitely to reduce ulcer recurrence.

Careful considerations regarding the cardiovascular and GI risks and benefits must be discussed in patients who need secondary cardiovascular prophylaxis; these patients commonly need to resume low-dose aspirin therapy. A follow up endoscopy should be performed in patients with gastric ulcers to assess healing, as a significant number of these lesions are related to an underlying malignancy.

Patients with variceal bleeding must be monitored in the hospital until completion of a continuous IV octreotide infusion as above. They will need to undergo ongoing endoscopic surveillance and management as per national guidelines.

Patients with ongoing occult GI blood loss should have considerations regarding serial hemoglobins and iron studies with considerations for adequate iron repletion.

What's the evidence?

Dallal, HJ, Palmer, KR. "ABC of the upper gastrointestinal tract: Upper gastrointestinal haemorrhage". BMJ. vol. 323. 2001. pp. 115-7.

(Provides a nice overview of management and etiologies of upper GI tract bleeding.)

Lau, JY, SUng, JJ, Lee, KK. "Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers". N Engl J Med. vol. 343. 2000. pp. 310-6.

(Provides evidence of benefits of high-dose infusion of a PPI reducing the risk of recurrent bleeding.)

Jensen, DM, Kovacs, TO, Jutabha, R. "Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots". Gastroenterology. vol. 123. 2002. pp. 407-13.

(Provides evidence regarding management of bleeds with adherent clot. Favors endoscopic intervention.)

Garcia-Tsao, G, Bosch, J. "Management of varices and variceal hemorrhage in cirrhosis". N Engl J Med. vol. 362. 2010. pp. 823-82.

(Provides a review of the management of variceal hemorrhage.)

Ahmed, A, Bruno, JM, Boynton, R. "Nasogastric aspirates frequently lead to erroneous results and delay therapy in patients with suspected UGI bleeding". Gastrointest Endosc. vol. 59. 2004. pp. 163.

(Provides some evidence and important reservations regarding the routine use of NG lavage in evaluating acute GI bleeding.)

Laine, L, Shah, A. "Randomized trial of urgent vs elective colonoscopy in patients hospitalized with lower GI bleeding". Am J Gastroenterol. vol. 105. 2010. pp. 2636-41.

(Provides an RCT of patients with serious hematochezia. Showed no improvement in performing an urgent colonoscopy rather than elective, providing logic for initial EGD followed by routine colonoscopy.)

Concha, R, Amaro, R, Barkin, JS. "Obscure gastrointestinal bleeding: diagnostic and therapeutic approach". J Clin Gastroenterol. vol. 41. 2007. pp. 242-51.

(Provides a review of management of obscure GI bleeding.)

Sami, SS, Al-Araji, SA, Ragunath, K. "Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis, and management". Aliment Pharmacol Ther. vol. 39. 2014. pp. 15-34.

(Provides a review of management of angiodyplasias of the GI tract.)

Laine, L, Jensen, DM. "Management of patients with ulcer bleeding". Am J Gastroenterol. vol. 107. 2012. pp. 345-60.

(ACG Practice guideline that provides a list of approximately 30 recommendations for pre- and post-endoscopic management of patients with ulcer bleeding, including follow-up for prevention of recurrence.)

Xin, L, Liao, Z, Jiang, YP. "Indications, detectability, positive findings, total enteroscopy, and complications of diagnostic double-balloon endoscopy: a systematic review of data over the first decade of use". Gastrointest Endosc. vol. 74. 2011. pp. 563-570.

(Provides a recent review on double-balloon enteroscopy.)

Sreedharan, A, Martin, J, Leontiadis, GI. "Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding". Cochrane Database Syst Rev. 2010. pp. 7.

(Provides a review of the use of PPI therapy prior to endoscopy for UGIB. Although no clear evidence of any improvement in mortality, rebleeding, or surgery was found, there is evidence that it may reduce the proportion of patients requiring endoscopic therapy.)

"The role of endoscopy in the patient with lower GI bleeding". Gastrointest Endosc. vol. 79. 2014. pp. 875-85.

(Guidelines by the ASGE regarding the role of endoscopy and diagnostic and therapeutic strategies in GI bleeding.)

"The role of endoscopy in the management of obscure GI bleeding". Gastrointest Endosc. vol. 72. 2010. pp. 471-9.

(Guidelines by the ASGE regarding the role of endoscopy and diagnostic and therapeutic strategies in GI bleeding.)

"The role of endoscopy in the management of variceal hemorrhage". Gastrointest Endosc. vol. 80. 2014. pp. 221-7.

(Guidelines by the ASGE regarding the role of endoscopy and diagnostic and therapeutic strategies in GI bleeding.)

"The role of endoscopy in acute non-variceal upper-GI hemorrhage". Gastrointest Endosc. vol. 60. 2004. pp. 497-504.

(Guidelines by the ASGE regarding the role of endoscopy and diagnostic and therapeutic strategies in GI bleeding.)
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