What is the differential diagnosis for melena (dark black tarry stools) in a patient taking apixaban (Eliquis)?

Differential Diagnosis for Melena in a Patient Taking Apixaban (Eliquis)

In a patient on apixaban presenting with melena, peptic ulcer disease is the most likely diagnosis (accounting for 35-50% of upper GI bleeding cases), followed by gastroduodenal erosions (8-15%), and esophagitis (5-15%), with the anticoagulant significantly amplifying bleeding risk from any underlying lesion. 1, 2

Primary Upper Gastrointestinal Sources (Most Common)

The vast majority of melena originates from upper GI sources proximal to the ligament of Treitz:

• Peptic ulcer disease represents the leading cause at 35-50% of cases, typically associated with Helicobacter pylori infection or chronic NSAID use 1, 2
• Gastroduodenal erosions account for 8-15% of cases, commonly linked to NSAID use, stress, or metabolic conditions 2
• Esophagitis causes 5-15% of melena presentations and is more frequently associated with melena than frank hematemesis 2
• Mallory-Weiss tears represent approximately 15% of cases, characteristically occurring after forceful vomiting or retching 2, 3
• Esophageal varices cause 5-10% of upper GI bleeding overall, though these typically present with massive hematemesis rather than melena in patients with known cirrhosis 2

Anticoagulant-Specific Considerations

Apixaban significantly increases the risk of GI bleeding from any underlying lesion, with DOACs specifically associated with increased gastrointestinal and genitourinary tract bleeding risk. 4, 5

Key anticoagulant-related factors:

• Apixaban has the most favorable GI safety profile among DOACs, with lower bleeding risk than rivaroxaban (HR 0.33) or dabigatran (HR 0.39) 5
• However, all DOACs increase baseline bleeding risk and should be used cautiously in patients with GI tract lesions or pathology 4
• Median time to GI bleeding on apixaban is less than 90 days after initiation 5
• Risk increases dramatically in patients ≥75 years old, though apixaban maintains the most favorable profile even in the very elderly 5

Less Common but Critical Upper GI Sources

Several rarer etiologies must be considered, particularly in patients without typical risk factors:

• Dieulafoy lesion accounts for 1-2% of acute bleeding, consisting of a tortuous submucosal artery penetrating the mucosa, commonly at the posterior gastric wall 2
• Cameron's erosions in large hiatal hernias are commonly overlooked causes of melena 1
• Gastric antral vascular ectasia occurs particularly in patients with chronic kidney disease or cirrhosis 1
• Aortoenteric fistula is rare but catastrophic, especially in patients with prior abdominal aortic aneurysm repair 1, 2
• Hemobilia and hemosuccus pancreaticus together account for approximately 1 in 500 cases of upper GI bleeding 1, 2
• Upper GI malignancy and vascular malformations each represent approximately 1% of cases 2

Lower Gastrointestinal Sources (When Upper Endoscopy is Negative)

Approximately 10-15% of patients presenting with melena have a lower GI origin of bleeding, making colonoscopy necessary when upper endoscopy is unrevealing. 1

Lower GI sources to consider:

• Diverticulosis is the most common lower GI source in older adults, accounting for 20-41% of lower GI bleeding cases 1
• Angiodysplasia contributes to 3-40% of lower GI bleeding and up to 80% of obscure bleeding, especially in patients over 40 years 1
• Ischemic colitis represents 10-21% of lower GI bleeding episodes, occurring more frequently in elderly patients with cardiovascular disease 1
• Colorectal cancer or polyps account for 6-27% of cases, with prevalence increasing in older populations 1
• Small bowel sources including angiodysplasia (up to 80% of obscure bleeding in patients >40 years) and small bowel tumors (most common cause in patients <50 years) 1

Rare Anticoagulant-Specific Complication

• Intramural hematoma causing intussusception has been reported with apixaban, though extremely rare, presenting as small bowel obstruction 6

Age-Related Risk Stratification

Patients over 65 years have markedly higher mortality from melena (up to 30% in those >90 years) and require more aggressive management. 1

Critical risk factors predicting severe bleeding and mortality:

• Hemodynamic instability (heart rate >100 bpm, systolic BP <100 mmHg) confers approximately 80% risk of ongoing bleeding or death 1
• Presence of serious comorbidities (cardiovascular disease, renal insufficiency, liver disease, malignancy) is the strongest predictor of death 1
• Virtually all fatalities occur in patients with significant medical comorbidities 1

Diagnostic Approach

Esophagogastroduodenoscopy (EGD) is the initial procedure of choice, ideally performed within 24 hours in hemodynamically stable patients, as it provides both diagnostic and therapeutic capabilities. 1

Diagnostic algorithm:

1. Confirm true melena (black, tarry, sticky consistency with characteristic odor) versus simple black stools from dietary causes or medications 1, 7
2. Assess hemodynamic stability and resuscitate before endoscopy—performing endoscopy before adequate resuscitation is a critical error that increases mortality 1
3. Perform EGD with attention to blind areas (high lesser curve, under incisura angularis, posterior duodenal bulb) using cap-fitted endoscopy 1
4. If EGD is negative, proceed to colonoscopy as 10-15% of melena originates from lower GI sources 1
5. If both negative, consider capsule endoscopy—the presence of melena doubles the odds (OR 1.97) of finding a bleeding site in the proximal small intestine 8
6. Deep enteroscopy should begin with an antegrade approach in patients with melena and negative initial workup 8

Management Priorities

• Correct coagulopathy as the first step in stable patients with underlying anticoagulation 4
• Transfuse to maintain hemoglobin >7 g/dL (or >9 g/dL with massive bleeding or cardiovascular comorbidities) 4, 1
• High-dose proton pump inhibitor therapy following successful endoscopic therapy for ulcer bleeding 1
• Address underlying causes: H. pylori eradication, acid suppression, and counsel regarding NSAID use 1