Harrison's Practice: Gastrointestinal Bleeding

Harrison's Practice

Gastrointestinal Bleeding

Definition

Bleeding from the GI tract may present in 5 ways.
- Hematemesis: vomitus of red blood or "coffee grounds" material
- Melena: black, tarry, foul-smelling stool
- Hematochezia: passage of bright red or maroon blood from the rectum
- Occult GI bleeding: blood in the stool in the absence of overt bleeding
- Symptoms of blood loss or anemia (e.g., lightheadedness or shortness of breath)
Upper GI bleeding
- Source in the upper GI tract (above the ligament of Treitz)
Lower GI bleeding
- Source in the small intestine or colon (below the ligament of Treitz)
Obscure GI bleeding
- Recurrent acute or chronic bleeding for which no known source is identified

Epidemiology

Incidence
- Hospital admissions for upper GI bleeding in the U.S. and Europe: approximately 100 per 100,000 persons annually
- Hospitalization rate for lower GI bleeding is about one-fifth that for upper GI bleeding.

Mechanism

Disruption of the GI mucosa secondary to inflammation, infection, trauma, or cancer
Vascular abnormalities, such as vascular ectasias or varices due to portal hypertension
See Differential Diagnosis for discussion of specific sources of GI bleeding.

Symptoms & Signs

Differentiation of upper GI bleeding from lower GI bleeding
- Hematemesis
  - Vomiting of blood or altered blood ("coffee grounds" appearance) indicates an upper GI source of bleeding (above the ligament of Treitz).
- Melena
  - Altered (black) blood passed by rectum (>100 mL blood for 1 melenic stool)
  - Indicates that blood has been present in the GI tract for at least 14 hours
  - Usually indicates bleeding proximal to ligament of Treitz, but may be as distal as ascending colon
  - The more proximal the bleeding site, the more likely melena will occur.
- Hematochezia
  - Bright red or maroon rectal bleeding
  - Usually represents a lower GI source of bleeding, although an upper GI lesion may bleed so briskly that blood does not remain in the bowel long enough for melena to develop.
  - When hematochezia is the presenting symptom of upper GI bleeding, it is associated with hemodynamic instability and decreasing hemoglobin concentration.
  - Bleeding lesions of the small bowel may present as melena or hematochezia.
  - Hematochezia that presents with abdominal pain may represent ischemic colitis, particularly in elderly persons or those with cardiovascular risk factors.
  - Hematochezia associated with diverticulosis and colonic tumors is typically painless.
- Other clues
  - Hyperactive bowel sounds and an elevated blood urea nitrogen level (due to volume depletion and blood proteins absorbed in the small intestine) suggest upper GI bleeding.
  - Nasogastric tube lavage usually, but not always, yields blood or "coffee grounds" material.
  - Nonbloody nasogastric aspirate may be seen in up to 18% of patients with upper GI bleeding.
    - Usually from a duodenal source
    - Bile-stained appearance does not exclude a bleeding postpyloric lesion because reports of bile in the aspirate are incorrect in about 50% of cases.
  - Mallory–Weiss tears usually occur in patients who have a history of vomiting, retching, or coughing preceding hematemesis, especially in an alcoholic patient.
  - Erosive gastropathy (subepithelial hemorrhages or erosions) is commonly related to NSAID use, alcohol intake, and stress.
  - Diverticular (colonic) bleeding is abrupt in onset, usually painless, sometimes massive, and often from the right colon; minor and occult bleeding is not characteristic.
Physical examination
- Clinically significant bleeding leads to postural changes in heart rate or blood pressure, tachypnea, tachycardia, and recumbent hypotension.
- Hemodynamic changes
  - Orthostatic decrease in blood pressure > 10 mmHg usually indicates > 20% reduction in blood volume.
  - Systolic blood pressure < 100 mmHg usually indicates > 30% reduction in blood volume.

Differential Diagnosis

Upper GI bleeding
- Ulcers (31–59%)
- Varices (7–20%), depending on group
- Mallory–Weiss tears (4–8%)
- Gastroduodenal erosions (2–7%)
- Erosive esophagitis (1–13%); major bleeding is rare
- Cancer (2–7%)
- Vascular ectasias (0–6%)
- No source identified (8–14%)
  - Possible causes: erosive duodenitis, aortoenteric fistulae, Dieulafoy’s lesion, prolapse gastropathy, hemobilia, hemosuccus pancreaticus
- Non-GI sources of bleeding
  - Generally involves swallowing blood from other sources
    - Epistaxis
    - Hemoptysis
- Pseudomelena
  - Ingestion of iron, bismuth, licorice, beets, blueberries, charcoal, or red-tinted foods (e.g., red gelatin)
Lower GI bleeding
- Diverticulosis (33–50%)
- Vascular ectasias (8–20% overall; more common in persons > 65 years of age)
- Tumors (19%)
  - Adenocarcinoma, leiomyoma, lymphoma, benign polyps, carcinoid, metastases, lipoma
- Colitis (18%)
  - Inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
  - Infection
  - Ischemic
  - Radiation-induced
- Hemorrhoids or anal fissures (5%)
- Meckel’s diverticulum
  - Most common cause of significant lower GI bleeding in children
  - With age, decreases in frequency as a cause of bleeding
- Less common causes
  - Vasculitis, small-bowel varices, duplication cysts, intussusception, polypectomy, rectal ulcers, rectal varices, lymphoid nodular hyperplasia, aortocolic fistulae
Chronic, obscure GI bleeding (recurrent iron-deficiency anemia or guaiac-positive stool of unknown source)
- Small-intestinal erosions and ulcers related to NSAID use
- In adults < 40–50 years of age, small-bowel tumors often account for obscure GI bleeding.
- In patients >50–60 years of age, vascular ectasias are usually responsible.

Diagnostic Approach

History and physical examination
- Focused history to identify risk factors (e.g., NSAID or alcohol use) and to evaluate likely source of bleeding
- Physical examination
  - Evaluate hemodynamic stability by measurement of heart rate and blood pressure.
  - Search for signs of an underlying disorder (e.g., liver disease).
  - Rectal examination is usually indicated; consider anoscopy if appropriate.
Laboratory evaluation
- Degree of anemia
Diagnostic procedures
- Upper endoscopy in patients with suspected upper GI bleeding
- Colonoscopy in patients with suspected lower GI bleeding
Other imaging studies, when indicated

Laboratory Tests

Complete blood count
- Hemoglobin concentration and hematocrit
  - May be normal initially in acute GI bleeding
  - Decrease as extravascular fluid enters the vascular space to restore volume
  - Patients with slow, chronic GI bleeding may have very low hemoglobin and hematocrit values despite normal blood pressure and heart rate.
- Mild leukocytosis and thrombocytosis are typical.
- Mean corpuscular volume and red-cell distribution width may be helpful in suggesting chronicity.
  - Expect microcytic anemia with elevated red-cell distribution width in iron-deficiency anemia related to chronic GI blood loss.
Serum chemistry
- Elevated blood urea nitrogen level is common in upper GI bleeding.
Occult blood testing
- Fecal occult blood test should be performed on stool that has passed naturally rather than that obtained from rectal examination to decrease the likelihood of false-positive results related to local trauma.
- Testing of nasogastric aspirates that are not grossly bloody is not useful.
Stool studies
- Fecal leukocytes may be present in conditions characterized by inflammation or infection.
- If infection is suspected, send stool cultures for evaluation of likely causes of infectious colitis.

Imaging

^99mTechnetium-labeled red-cell scintigraphy
- Can detect bleeding rate of 0.1–0.5 mL/min
- Used primarily as a screening test
  - When bleeding is intermittent and of unclear origin
  - To identify the general area of lower GI bleeding
  - To confirm that bleeding is rapid enough for arteriography to be of value
- Allows repeated imaging for up to 24 hours after initial injection of the patient’s radionuclide-labeled cells
- Perform in:
  - Patients with continued obscure GI bleeding who require transfusions or repeated hospitalizations
  - In diagnosis of Meckel’s diverticulum, especially in the evaluation of young patients
- Radionuclide scans should be interpreted with caution because results are highly variable, especially from later images.
Angiography
- Requires bleeding rate > 0.5 mL/min
- Can detect the site of bleeding in active lower GI bleeding (extravasation of contrast into the gut) and permits treatment with intra-arterial infusion of vasopressin or embolization
- Even after bleeding has stopped, angiography may identify lesions with abnormal vasculature, such as vascular ectasias or tumors.
Radiographic examination of small bowel (e.g., enteroclysis)
- If enteroscopy and video-capsule endoscopy are negative or unavailable
- May be considered in patients with iron-deficiency anemia
Upper GI barium radiography
- Accuracy ~80% in identifying an upper GI lesion
- Does not confirm source of bleeding
- Acceptable alternative to endoscopy in resolved or chronic low-grade bleeding
Selective mesenteric arteriography
- When brisk bleeding precludes identification of source at endoscopy
CT and MR enterography are newer imaging techniques currently being investigated.

Diagnostic Procedures

Upper endoscopy
- Test of choice in patients with upper GI bleeding
- Should be performed urgently to identify source of bleeding and allow intervention in patients with hemodynamic instability
  - Hypotension
  - Tachycardia
  - Postural changes in heart rate or blood pressure
- Patients with hematochezia and hemodynamic instability should have upper endoscopy before evaluation of the lower GI tract.
- Interventions can be performed to decrease bleeding, e.g., injection or cauterization of ulcers and ligation or sclerotherapy of bleeding varices.
- In patients with occult GI bleeding who have normal colonoscopy, upper endoscopy is usually recommended if iron-deficiency anemia or upper GI symptoms are present.
Colonoscopy
- Oral lavage solution followed by colonoscopy is the procedure of choice in patients admitted with lower GI bleeding unless:
  - Bleeding is too massive
  - Sigmoidoscopy has disclosed an obvious actively bleeding lesion
- Evaluation of a positive test for fecal occult blood generally should begin with colonoscopy, particularly in patients > 40 years of age.
Sigmoidoscopy
- Patients with presumed lower GI bleeding may undergo early sigmoidoscopy for the detection of obvious, low-lying lesions.
  - Difficult with brisk bleeding
  - Usually not possible to identify the area of bleeding
  - Useful primarily in patients < 40 years of age with minor bleeding
Push enteroscopy
- May identify probable bleeding sites in 20–40% of patients with obscure GI bleeding
Video-capsule endoscopy
- Allows endoscopic examination of the entire small intestine and increases diagnostic yield in obscure GI bleeding
  - Bleeding sites were identified in approximately 30–65% of cases in the initial published reports.
  - Lack of control of the capsule prevents its manipulation and full visualization of the intestine.
  - Tissue cannot be sampled, and therapy cannot be applied.
Double-balloon enteroscopy
- New endoscopic technique
- Allows the endoscopist to potentially examine and provide therapy to much or all of the small intestine.
Intraoperative endoscopy
- Indicated when all tests are unrevealing in patients with severe recurrent or persistent bleeding requiring repeated transfusions

Treatment Approach

Hemodynamic resuscitation and stabilization
Procedural intervention
- Endoscopic hemostatic therapy
- Colonoscopic removal of bleeding polyp or mass
- Surgical resection if necessary
Targeted medical therapy

Specific Treatments

Hemodynamic resuscitation and stabilization

Venous access
- Large-bore needle (14–18 gauge)
- Central venous line for major bleeding and patients with cardiac disease
Monitor vital signs, urine output, and hemoglobin and hematocrit (decrease may lag).
Gastric lavage is of unproven benefit but clears the stomach before endoscopy.
- Iced saline may lyse clots and reactivate bleeding; room-temperature tap water may be preferable.
Intubation may be required to protect the airway.
Support blood pressure with isotonic fluids (normal saline) and blood products as necessary.
Type and cross-match blood (6 units for major bleeding)
- Packed red blood cells
- Whole blood if massive bleeding
- Transfuse as necessary on the basis of clinical signs, with a target hematocrit > 25–30%.
Reverse coagulopathy (if present) with fresh-frozen plasma and vitamin K.
- Consider in cirrhotic patients or those taking anticoagulants.
Intravenous calcium (up to 10–20 mL 10% calcium gluconate IV over 10–15 min) if serum calcium level decreases due to transfusion of citrated blood
Surgical standby when bleeding is massive
Indications for emergency surgery
- Uncontrolled or prolonged bleeding, severe rebleeding, aortoenteric fistula
- For intractable variceal bleeding, consider transjugular intrahepatic portosystemic shunt (TIPS).
- One-third of patients with active bleeding or a nonbleeding visible vessel have further bleeding that requires urgent surgery if they are treated conservatively.

Upper GI bleeding

Peptic ulcers
- Endoscopic therapy with bipolar electrocoagulation, heater probe, or injection therapy (e.g., absolute alcohol, 1:10,000 epinephrine) if indicated
- High-dose, constant IV infusion of proton-pump inhibitor (PPI), to increase intragastric pH to >6 and enhance clot stability
  - Decreases further bleeding, need for surgery, and repeat endoscopy[1]
  - No effect on mortality except possibly in patients with high-risk ulcers (active bleeding, nonbleeding visible vessel)[1]
  - Many clinical trials have used intravenous omeprazole.
  - In the U.S., pantoprazole and lansoprazole are the PPIs that are available in an intravenous formulation.
    - IV pantoprazole: initial dose, 80-mg bolus, followed by 8 mg/h
    - IV lansoprazole: initial dose, 60-mg bolus, followed by 6 mg/h
- Eradication of Helicobacter pylori in patients with bleeding ulcers decreases rates of rebleeding to < 5%.
- If a bleeding ulcer develops in a patient taking NSAIDs, the NSAID therapy should be discontinued if possible.
  - If NSAID therapy must be continued, treatment with a PPI should be continued, and the risk–benefit profile of switching to a cyclooxygenase 2 (COX-2)–specific inhibitor (coxib) should be carefully reviewed.
  - Among nonselective NSAIDs, risk of bleeding seems to be lowest for ibuprofen.
  - Either PPI co-therapy with a nonselective NSAID or use of a coxib alone is associated with an annual rebleeding rate of ~10% in high-risk patients (i.e., a recent bleeding ulcer).
  - Combination of a coxib and PPI provides a further significant decrease in ulcers and recurrent bleeding and should be employed in very high-risk patients.
  - Use of misoprostol (100 μg tid or qid, increasing to 200 μg tid or qid, if necessary) can prevent NSAID GI toxicity.
- Patients with bleeding ulcers unrelated to H. pylori or NSAIDs should continue to receive full-dose antisecretory therapy indefinitely.
- Patients with clean-based ulcers may be discharged on the first hospital day after stabilization if there is no other reason for hospitalization.
- Patients without clean-based ulcers should usually remain in the hospital for 3 days as most episodes of recurrent bleeding occur within this time frame.
Mallory–Weiss tears
- Bleeding usually occurs on the gastric side of the gastroesophageal junction.
- Stops spontaneously in 80–90% of patients
- Endoscopic therapy is indicated for active bleeding.
- Angiographic therapy with intra-arterial infusion of vasopressin or embolization and operative therapy with oversewing of the tear are rarely required.
Esophageal varices
- Endoscopic therapy for acute bleeding and repeated sessions of endoscopic therapy to eradicate esophageal varices significantly reduces rebleeding and mortality.
- Ligation is the endoscopic therapy of choice for esophageal varices compared with sclerotherapy.
  - Less rebleeding
  - Lower mortality rate
  - Fewer local complication
  - Fewer treatment sessions to achieve variceal eradication
- Short-term treatment with octreotide (50-μg bolus and 50-μg/h IV infusion for 2–5 days) may help control acute bleeding.
  - Has replaced vasopressin as the medical therapy of choice for acute variceal bleeding
  - Somatostatin and terlipressin, available outside the U.S., are also effective.
- Antibiotic therapy (e.g., quinolones) is also recommended for patients with cirrhosis presenting with upper GI bleeding, as antibiotics decrease bacterial infections and mortality in this population.
- Long-term treatment with nonselective beta blockers decreases recurrent bleeding from esophageal varices.
  - Commonly given along with long-term endoscopic therapy.
- In patients who have persistent or recurrent bleeding despite endoscopic and medical therapy, more invasive therapy is warranted.
  - TIPS decreases rebleeding more effectively than endoscopic therapy, although hepatic encephalopathy is more common and mortality rates are similar.
  - Most patients with TIPS have shunt stenosis within 1–2 years and require reinstrumentation, although the use of coated stents appears to markedly decrease shunt dysfunction, at least in the first year.
  - TIPS is most appropriate for patients with more severe liver disease and those in whom transplant is anticipated.
  - Patients with milder, well-compensated cirrhosis require fewer re-interventions with decompressive surgery (e.g., distal splenorenal shunt), although the higher initial risks of surgery must also be considered.
- Portal hypertension is also responsible for bleeding from gastric varices, varices in the small and large intestine, and portal hypertensive gastropathy and enterocolopathy.
Hemorrhagic and erosive gastropathy ("gastritis")
- Removal of the offending agent if possible (e.g., NSAIDs, alcohol).
- Multiple trials document the efficacy of intravenous H₂-receptor antagonist therapy, which is more effective than sucralfate but not superior to a PPI immediate-release suspension given via nasogastric tube.

Small-intestinal bleeding

Vascular ectasias
- Treated with endoscopic therapy if possible.
- Surgical therapy can be used for vascular ectasias isolated to a segment of the small intestine when endoscopic therapy is unsuccessful.
- Estrogen/progesterone compounds have been used for vascular ectasias, but a double-blind trial found no benefit in prevention of recurrent bleeding.
- Isolated lesions, such as tumors, diverticula, or duplications, are generally treated with surgical resection.

Colonic bleeding

Bleeding colonic diverticula stop bleeding spontaneously in approximately 80% of patients.
- Intra-arterial vasopressin or embolization by superselective technique should stop bleeding in a majority of patients.
- If bleeding persists or recurs, segmental surgical resection is indicated.
Endoscopic polypectomy, if possible, is used to treat bleeding colonic polyps.
Colonic tumors typically require surgical resection.
Bleeding from right colonic vascular ectasias in elderly persons tends to be chronic and only occasionally is hemodynamically significant.
Surgical therapy is generally required for major, persistent, or recurrent bleeding from the wide variety of colonic sources of GI bleeding that cannot be treated medically or endoscopically.

Monitoring

Patients with acute GI bleeding typically require hospitalization.
Patients with subacute or chronic GI bleeding may undergo outpatient evaluation if they do not have significant comorbid conditions.
Patients who present with active GI bleeding require close monitoring.
Intensive care unit may be indicated for patients with hemodynamic instability, those requiring blood transfusions, and those with continued active bleeding.
After endoscopy
- Patients with lower-risk endoscopic findings (clean-based ulcer) may be discharged on medical therapy.
- Patients with higher-risk endoscopic findings (active bleeding or visible vessel) require continued inpatient monitoring for several days.
After colonoscopy, the level of monitoring may be determined by whether definitive intervention has eliminated source of bleeding.

Complications

Hypovolemic shock and subsequent end-organ damage
Complications related to blood transfusions, such as acquired infections or transfusion reaction
Complications related to procedural interventions, such as perforation and infection

Prognosis

Upper GI bleeding
- Mortality rate of ~5%–10%
  - < 1% in patients < 60 years of age in the absence of major concurrent illness
- Patients rarely die of exsanguination; rather, they die of decompensation from other underlying illnesses.
- Adverse prognostic signs
  - 3 independent clinical predictors of death in patients hospitalized with upper GI bleeding
    - Increasing age
    - Comorbid conditions
    - Hemodynamic compromise (tachycardia or hypotension)
  - Other poor prognostic signs: coagulopathy, immunosuppression, presentation with shock, rebleeding, onset of bleeding in hospital, variceal bleeding, endoscopic stigmata of recent bleeding
- Peptic ulcer
  - Patients with clean-based ulcers have a rate of recurrent bleeding of approximately 5% and a mortality rate of approximately 2%.
  - Patients with actively bleeding ulcers at endoscopy have a rebleeding rate of approximately 50% and a mortality rate of approximately 10%.
- Mallory–Weiss tears
  - Bleeding recurs in 0–7% of patients.
- Esophageal varices
  - Patients with variceal hemorrhage have poorer outcomes than patients with other sources of upper GI bleeding.
- Stress-related gastric mucosal injury
  - Mortality rate is high because of serious underlying illness.
Lower GI bleeding
- Bleeding colonic diverticula
  - Approximately 20–25% of patients have episodes of rebleeding.

Prevention

Prevention of recurrent bleeding is focused on treatment of the underlying cause.
Examples
- Recurrent bleeding ulcer
  - Address 3 main factors in ulcer pathogenesis.
    - Treat Helicobacter pylori infection.
    - Discontinue NSAID therapy.
    - Provide acid suppression with a PPI.
- Esophageal varices
  - Nonselective beta blocker to decrease portal hypertension
  - TIPS for severe disease
- GI cancer
  - Treatment of underlying condition and surgery if appropriate
- Angiodysplasia
  - Rebleeding risk may be as high as 30% after local therapy (endoscopic coagulation).
  - Usual source is another lesion rather than the same lesion.

ICD-9-CM

578.9 Hemorrhage of gastrointestinal tract, unspecified