Gastrointestinal Bleeding With Normal Endoscopy: Where Else to Look?

Dr Neeraj Manikath ,claude.ai

Abstract

Gastrointestinal bleeding with normal upper and lower endoscopy, termed obscure gastrointestinal bleeding (OGIB), presents a significant diagnostic challenge in critical care and gastroenterology. This review examines the systematic approach to identifying bleeding sources beyond the reach of conventional endoscopy, with particular emphasis on small bowel arteriovenous malformations, Dieulafoy lesions, aortoenteric fistulae, and angiodysplasia. We discuss the evolving role of capsule endoscopy and CT angiography in diagnostic algorithms, providing evidence-based recommendations for postgraduate trainees in critical care medicine.

Keywords: Obscure gastrointestinal bleeding, capsule endoscopy, CT angiography, small bowel bleeding, arteriovenous malformation

Introduction

Obscure gastrointestinal bleeding (OGIB) accounts for 5-10% of all gastrointestinal bleeding cases and represents one of the most challenging diagnostic scenarios in acute medicine. Defined as bleeding from the gastrointestinal tract that persists or recurs without an obvious source identified on upper endoscopy, colonoscopy, and radiological evaluation of the small bowel, OGIB can be further classified as obscure-overt (visible bleeding) or obscure-occult (iron deficiency anemia or positive fecal occult blood test without visible bleeding).

The small bowel, comprising approximately 75% of the gastrointestinal tract length and 90% of its surface area, remains the most common site of bleeding in OGIB cases. Recent advances in diagnostic modalities, particularly capsule endoscopy and multidetector CT angiography, have revolutionized our approach to these complex cases.

Clinical Presentation and Initial Assessment

Pearl 1: The "Rule of Thirds"

In patients with OGIB, the bleeding source distribution follows a predictable pattern: approximately one-third originate from the small bowel, one-third from missed lesions in the upper or lower GI tract, and one-third remain unidentified despite extensive investigation.

Oyster 1: The Timing Trap

A common misconception is that acute bleeding always requires emergency intervention. However, in hemodynamically stable patients with OGIB, rushing to invasive procedures without proper planning often leads to missed diagnoses and repeated procedures.

The initial assessment should focus on:

Hemodynamic stability and transfusion requirements
Medication history (anticoagulants, NSAIDs, antiplatelet agents)
Comorbidities (cirrhosis, chronic kidney disease, connective tissue disorders)
Physical examination for stigmata of inherited bleeding disorders

Hack 1: The Aspirin Challenge

In patients with recurrent OGIB and no obvious bleeding source, consider a supervised aspirin challenge (75-100mg daily) in stable patients. This can unmask occult small bowel lesions by precipitating bleeding, making subsequent imaging more diagnostic.

Specific Bleeding Sources

Small Bowel Arteriovenous Malformations (AVMs)

Small bowel AVMs represent the most common cause of small bowel bleeding in patients over 40 years of age. These lesions are characterized by abnormal communications between arteries and veins, bypassing the normal capillary bed.

Pathophysiology

AVMs develop secondary to chronic mucosal ischemia, leading to the formation of arteriovenous communications. The degenerative process is accelerated by conditions causing chronic hypoxemia or reduced cardiac output.

Clinical Features

Intermittent bleeding with iron deficiency anemia
More common in elderly patients
Associated with aortic stenosis (Heyde's syndrome)
May present with massive bleeding

Diagnostic Approach

Capsule endoscopy demonstrates a sensitivity of 83-89% for detecting small bowel AVMs, significantly superior to push enteroscopy (28-35%) or CT angiography (47-52%).

Pearl 2: Heyde's Syndrome Recognition

The triad of aortic stenosis, acquired von Willebrand disease, and gastrointestinal bleeding should prompt investigation for small bowel AVMs, even in the absence of obvious bleeding.

Dieulafoy Lesions

Dieulafoy lesions are dilated aberrant submucosal arteries that protrude through a mucosal defect without associated ulceration. While classically described in the stomach, these lesions can occur throughout the gastrointestinal tract.

Characteristics

Arterial caliber 1-3mm (normal submucosal vessels: 0.1-0.2mm)
Minimal mucosal abnormality
Tendency for massive bleeding due to arterial nature
Male predominance (2:1 ratio)

Small Bowel Dieulafoy Lesions

These represent 1-2% of all Dieulafoy lesions but are particularly challenging to diagnose due to:

Intermittent bleeding pattern
Minimal endoscopic findings between bleeding episodes
Location in the proximal jejunum (most common)

Oyster 2: The Invisible Culprit

Dieulafoy lesions can appear as minimal mucosal irregularities or even normal mucosa between bleeding episodes. Active bleeding or recent hemorrhage may be the only clue to their presence.

Aortoenteric Fistulae

Aortoenteric fistulae represent a surgical emergency with high mortality rates if not promptly recognized and treated. These abnormal communications between the aorta and intestinal tract are classified as primary (rare) or secondary (following aortic surgery).

Primary Aortoenteric Fistulae

Incidence: 0.04-0.07% of all gastrointestinal bleeding
Usually involve the third or fourth portion of the duodenum
Associated with aortic aneurysms, atherosclerosis, or infection

Secondary Aortoenteric Fistulae

Occur in 0.5-2% of patients following aortic reconstruction
Median time to presentation: 3-5 years post-surgery
Most commonly involve aortic grafts

Clinical Presentation

The classic triad includes:

Gastrointestinal bleeding
Abdominal pain
Palpable abdominal mass

Hack 2: The Herald Bleed

Up to 75% of patients with aortoenteric fistulae experience a "herald bleed" - a self-limited bleeding episode that precedes massive hemorrhage by hours to days. This represents a critical window for intervention.

Diagnostic Approach

CT angiography with IV contrast: sensitivity 94%, specificity 85%
Upper endoscopy may show blood in the duodenum without an obvious source
Angiography is often negative due to intermittent bleeding

Angiodysplasia

Angiodysplasia represents acquired vascular malformations that increase in prevalence with age. These lesions account for 30-40% of small bowel bleeding sources in patients over 60 years.

Pathophysiology

Chronic, low-grade obstruction of submucosal veins leads to dilatation and arteriovenous communication formation. The process is exacerbated by:

Chronic kidney disease
von Willebrand disease
Hereditary hemorrhagic telangiectasia

Distribution

Cecum and ascending colon: 70%
Small bowel: 15%
Stomach and duodenum: 15%

Pearl 3: The Chronic Kidney Disease Connection

Patients with chronic kidney disease have a 20-30 fold increased risk of angiodysplasia-related bleeding, attributed to platelet dysfunction and increased angiogenesis.

Advanced Diagnostic Modalities

Capsule Endoscopy

Capsule endoscopy has revolutionized the diagnosis of small bowel bleeding, providing non-invasive visualization of the entire small bowel mucosa.

Technical Considerations

Diagnostic yield: 60-70% in OGIB patients
Optimal timing: within 48-72 hours of bleeding episode
Contraindications: known or suspected bowel obstruction, pacemaker or implantable cardioverter-defibrillator (device-dependent)

Limitations

Cannot provide therapeutic intervention
Risk of capsule retention: 1-2% in patients without known strictures
Requires adequate bowel preparation

Hack 3: The Bleeding Predictor Score

Patients with age >65 years, hemoglobin <10 g/dL, and ongoing bleeding have a >90% likelihood of finding a bleeding source on capsule endoscopy.

CT Angiography

Multidetector CT angiography has emerged as a valuable diagnostic tool, particularly in the acute setting.

Technical Requirements

Minimum bleeding rate: 0.3-0.5 mL/min for detection
Optimal timing: during active bleeding
Protocol: non-contrast, arterial phase, portal venous phase, and delayed phase imaging

Advantages

Rapid acquisition
Widely available
Can guide subsequent therapeutic intervention
Provides anatomical localization

Diagnostic Yield

Active bleeding: sensitivity 85-95%, specificity 95-99%
Vascular malformations: sensitivity 70-85%, specificity 80-95%

Oyster 3: The Timing Dilemma

CT angiography is most effective during active bleeding, but many patients stop bleeding by the time imaging is performed. Consider provocative agents (anticoagulation, thrombolytics) in select cases under controlled conditions.

Diagnostic Algorithm

Initial Assessment

Confirm absence of upper and lower GI sources
Review medications and comorbidities
Assess bleeding severity and hemodynamic status

Acute Bleeding (Hemodynamically Unstable)

Immediate CT angiography if bleeding rate >0.5 mL/min
Urgent angiography with embolization if positive
Surgical consultation if angiography unsuccessful

Chronic/Intermittent Bleeding

Capsule endoscopy as first-line investigation
CT angiography if capsule negative and high clinical suspicion
Device-assisted enteroscopy if lesion identified on capsule endoscopy

Management Strategies

Medical Management

Iron supplementation for chronic blood loss
Correction of coagulopathy
Treatment of underlying conditions (heart failure, chronic kidney disease)

Endoscopic Therapy

Argon plasma coagulation for angiodysplasia
Injection therapy for Dieulafoy lesions
Clip placement for accessible lesions

Angiographic Intervention

Selective embolization for active bleeding
Vasopressin infusion (rarely used)
Covered stent placement for aortoenteric fistulae (bridge to surgery)

Surgical Management

Reserved for failed endoscopic/angiographic therapy
Aortoenteric fistulae require emergency surgical repair
Segmental resection for localized lesions

Emerging Technologies

Artificial Intelligence in Capsule Endoscopy

Machine learning algorithms are being developed to improve detection rates and reduce reading time for capsule endoscopy studies, with early results showing promise in identifying bleeding sources.

Coil-Assisted Capsule Endoscopy

Magnetic steering systems allow for controlled navigation of capsule endoscopes, potentially improving visualization of specific areas of interest.

Clinical Pearls and Oysters Summary

Additional Pearls

Pearl 4: In patients with hereditary hemorrhagic telangiectasia, pulmonary arteriovenous malformations may coexist with GI bleeding. Always screen for these potentially life-threatening lesions.
Pearl 5: Octreotide can be used as bridging therapy in patients with recurrent bleeding from small bowel angiodysplasia while awaiting definitive treatment.

Additional Oysters

Oyster 4: Normal capsule endoscopy does not exclude small bowel bleeding sources. Up to 25% of patients with negative capsule studies have positive findings on repeat examination.
Oyster 5: Anticoagulation reversal in patients with mechanical heart valves and GI bleeding requires careful risk-benefit analysis and multidisciplinary consultation.

Conclusion

The management of gastrointestinal bleeding with normal endoscopy requires a systematic approach combining clinical acumen with appropriate utilization of advanced diagnostic modalities. Capsule endoscopy remains the gold standard for small bowel evaluation, while CT angiography provides valuable information in the acute setting. Recognition of specific bleeding sources and their characteristic presentations is crucial for optimal patient outcomes.

Future developments in artificial intelligence and interventional techniques promise to further improve diagnostic yields and therapeutic options for these challenging cases. The key to success lies in early recognition, appropriate investigation sequencing, and timely intervention when indicated.

References

Gerson LB, Fidler JL, Cave DR, et al. ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding. Am J Gastroenterol. 2015;110(9):1265-1287.
Pennazio M, Spada C, Eliakim R, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2015;47(4):352-376.
Leung WK, Ho SS, Suen BY, et al. Capsule endoscopy or angiography in patients with acute overt obscure gastrointestinal bleeding: a prospective randomized study with long-term follow-up. Am J Gastroenterol. 2012;107(9):1370-1376.
García-Compean D, Jiménez-Rodríguez AR, Gonzalez-González JA, et al. Dieulafoy lesions of the small bowel: case series and literature review. World J Gastrointest Endosc. 2019;11(2):83-89.
Saers SJF, Scheltinga MRM. Primary aortoenteric fistula. Br J Surg. 2005;92(2):143-152.
Holleran G, Hall B, Hussey M, et al. Small bowel angiodysplasia and novel disease associations: a cohort study. Scand J Gastroenterol. 2013;48(4):433-438.
Yung DE, Rondonotti E, Giannakou A, et al. Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy. United European Gastroenterol J. 2017;5(7):974-981.
Blomberg J, Leinonen P, Lepistö A, et al. CT angiography in the diagnosis of acute lower gastrointestinal bleeding. Eur J Radiol. 2014;83(11):2074-2081.
Akyuz F, Pinarbasi B, Ermis F, et al. Is capsule endoscopy effective in patients presenting with small bowel bleeding? A systematic review. World J Gastroenterol. 2015;21(12):3669-3677.
Höög CM, Bark LÅ, Arkani J, et al. Capsule retentions and incomplete capsule endoscopy examinations: an analysis of 2300 examinations. Gastroenterol Res Pract. 2012;2012:518718.
Gralnek IM, Ching JY, Maza I, et al. Capsule endoscopy in acute upper gastrointestinal hemorrhage: a prospective cohort study. Endoscopy. 2013;45(1):12-19.
Junquera F, Feu F, Papo M, et al. A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Gastroenterology. 2001;121(5):1073-1079.
Blackstone MO. Endoscopic interpretation: normal and pathologic appearances of the gastrointestinal tract. New York: Raven Press; 1984.
Raju GS, Gerson L, Das A, et al. American Gastroenterological Association (AGA) Institute medical position statement on obscure gastrointestinal bleeding. Gastroenterology. 2007;133(5):1694-1696.
Triester SL, Leighton JA, Leontiadis GI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol. 2005;100(11):2407-2418.

Friday, July 11, 2025