What are the most common causes of gastrointestinal (GI) bleed in adults, particularly in older adults with a history of bleeding disorders or those taking anticoagulant medications such as warfarin or aspirin?

Most Common Causes of Gastrointestinal Bleeding

Peptic ulcer disease is the most common cause of upper GI bleeding, accounting for approximately 43.6% of cases, with NSAID use now surpassing Helicobacter pylori as the leading identifiable risk factor. 1, 2

Primary Etiologies of Upper GI Bleeding

Peptic Ulcer Disease (43.6% of cases)

• NSAID use is found in 53% of patients with bleeding ulcers, making it the most commonly identified risk factor 1
• H. pylori infection remains a major contributor, though its prevalence has decreased with widespread eradication efforts 3, 2
• The combination of NSAIDs and aspirin increases relative risk of GI bleeding to more than 10-fold compared to either agent alone 1

Gastritis and Duodenitis (27.6% of cases)

• Represents the second most common cause of upper GI bleeding 2
• Often medication-related, particularly from NSAIDs and aspirin 1

Esophageal Variceal Bleeding (8.0% of cases)

• Third most common cause overall 2
• Primarily occurs in patients with portal hypertension from liver disease 4

Other Causes (Combined 10-12%)

• Esophagitis (5.6%) 2
• Malignancy 2
• Dieulafoy's lesions 2
• Mallory-Weiss tears 2

Critical Risk Factors in Older Adults on Anticoagulants

Medication-Related Risk (Highest Impact)

History of previous peptic ulcer or GI bleeding is the single strongest predictor, with odds ratios as high as 13.5 1, 5

Anticoagulant Effects

• Warfarin increases bleeding risk through multiple mechanisms, including inhibition of vitamin K-dependent clotting factors 6
• Reported risk factors for warfarin-associated bleeding include: INR >4.0, age ≥65 years, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, and concomitant drugs 6

NSAID Combinations

• NSAIDs have an odds ratio of 8.6 for GI bleeding in anticoagulated patients 5
• NSAIDs increase risk 3- to 5-fold in non-anticoagulated patients 1
• Even low-dose aspirin (75-325 mg/day) increases GI bleeding risk 2-4 times 1
• When aspirin is combined with other NSAIDs, relative risk exceeds 10-fold 1

Antiplatelet Agents

• Dual antiplatelet therapy increases GI bleeding risk 2- to 3-fold compared to aspirin alone 5
• Clopidogrel alone carries similar bleeding risk to low-dose aspirin 1

Corticosteroids

• Increase bleeding risk approximately 2-fold when combined with anticoagulants 5, 7
• More strongly associated with non-ulcer GI bleeds than peptic ulcers 8

Age-Related Risk

• Advanced age increases risk by approximately 4% per year 1, 7
• Age ≥75 years represents a major independent risk factor 7
• Older adults have higher prevalence of comorbidities and polypharmacy 1

H. pylori Infection

• Remains a consistent and modifiable predictor of GI bleeding in anticoagulated patients 5, 7
• Testing and eradication should be performed in high-risk patients 3

Risk Stratification Algorithm

Very High Risk (Requires PPI Prophylaxis)

• Prior GI bleeding or peptic ulcer AND any anticoagulant or antiplatelet agent 1, 5
• Two or more antithrombotic agents (anticoagulant + antiplatelet, or dual antiplatelet therapy) 1
• Anticoagulation + NSAID use 5

High Risk (Consider PPI Prophylaxis)

• Age >60-65 years + anticoagulant or antiplatelet therapy 1
• Single antiplatelet agent + one additional risk factor (H. pylori, corticosteroids, high alcohol use) 1, 7
• NSAID use with any risk factor (age >65, prior ulcer, high-dose therapy, concurrent aspirin or corticosteroids) 1

Moderate Risk (Selective PPI Use)

• Single antiplatelet or anticoagulant without additional risk factors 1
• NSAID use in younger patients without risk factors 1

Critical Clinical Pitfalls

Failing to Address H. pylori

• This treatable infection remains an independent and modifiable risk factor 5
• Test and treat before initiating long-term anticoagulation or antiplatelet therapy in high-risk patients 3

Assuming Enteric-Coated or Buffered Aspirin is Safer

• The relative risks of upper GI bleeding for plain, enteric-coated, and buffered aspirin at 325 mg daily were 2.6,2.7, and 3.1 respectively—essentially equivalent 1
• No aspirin formulation eliminates bleeding risk 1

Underestimating Lower GI Tract Complications

• Lower GI complications from NSAIDs may account for 20% of total NSAID-associated GI morbidity 1
• Incidence of lower GI bleeding has remained stable (43-45 per 100,000) despite decreasing upper GI bleeding rates 8, 2

Inadequate PPI Prophylaxis in High-Risk Patients

• PPIs should not be de-prescribed in patients at high risk for GI bleeding (age >60 years, severe comorbidity, using second NSAID or aspirin, taking antithrombotic, or taking corticosteroid) 1
• PPIs reduce upper GI bleeding risk by approximately 75-85% in high-risk patients 7