How to manage an upper gastrointestinal (GI) bleed in a patient with hemophilia?

Management of Upper GI Bleeding in Hemophilia

Immediately initiate factor replacement therapy (Factor VIII or IX concentrate) to achieve hemostatic levels (50-100% activity) and maintain for at least 2-7 days, combined with standard upper GI bleeding management including high-dose IV PPI therapy and urgent endoscopy within 24 hours after hemodynamic stabilization. 1

Immediate Hemostatic Management

Factor Replacement Therapy (First Priority)

• Administer Factor VIII or IX concentrate immediately to achieve 50-100% factor activity levels before any diagnostic or therapeutic procedures 1
• For hemophilia A: Target Factor VIII levels of 50-100 IU/dL (0.50-1.0 U/mL) for severe bleeding 1
• For hemophilia B: Target Factor IX levels of 50-100 IU/dL 1
• Maintain factor replacement for minimum 2 days, though 7-14 days may be required for severe bleeding - evidence suggests short-term (2-day) replacement may be sufficient when combined with effective endoscopic hemostasis 2

Bypassing Agents (If Inhibitors Present)

• If Factor VIII inhibitors are present, use recombinant Factor VIIa (rFVIIa) 90 mcg/kg IV every 2-3 hours until hemostasis is achieved 1
• Alternative: Activated prothrombin complex concentrates (aPCC) 50-100 IU/kg every 8-12 hours (maximum 200 IU/kg/day) 1
• GI bleeding is specifically highlighted as requiring anti-hemorrhagic treatment in acquired hemophilia, with mortality from GI bleeding occurring within the first week in fatal cases 1

Resuscitation and Stabilization

Fluid and Blood Product Management

• Initiate crystalloid resuscitation immediately with goal of heart rate reduction, blood pressure increase, and urine output >30 mL/hour 3
• Transfuse red blood cells when hemoglobin <80 g/L in patients without cardiovascular disease; use higher threshold if cardiovascular disease present 3, 4
• Avoid over-transfusion as restrictive strategy (Hgb <80 g/L) improves outcomes 3

Critical Monitoring

• Monitor hemoglobin/hematocrit frequently as this is more reliable than imaging for assessing ongoing bleeding 1
• Measure factor levels before and during treatment to ensure adequate hemostatic levels 5, 2
• Assess for hemodynamic instability (heart rate >100 bpm, systolic BP <100 mmHg) which indicates high-risk bleeding 4

Pharmacologic Management

Proton Pump Inhibitor Therapy

• Start high-dose IV PPI immediately upon presentation before endoscopy 3, 4
• After successful endoscopic therapy: Administer pantoprazole 80 mg IV bolus followed by 8 mg/hour continuous infusion for 72 hours 3, 4
• Continue oral PPI twice daily through day 14, then once daily for duration based on underlying cause 3, 4

Antifibrinolytic Agents - CRITICAL CAVEAT

• Tranexamic acid is CONTRAINDICATED when used in conjunction with aPCC per FDA prescribing information 6
• Use of antifibrinolytics with bypassing therapy remains controversial 1
• If used, tranexamic acid dosing: 10 mg/kg IV 3-4 times daily for 2-8 days, infused no faster than 1 mL/minute 6

Endoscopic Management

Timing and Preparation

• Perform endoscopy within 24 hours after hemodynamic stabilization in all hospitalized patients 3, 4
• Consider urgent endoscopy within 12 hours for high-risk patients with persistent hemodynamic instability after initial resuscitation 3, 4
• Ensure Factor VIII/IX levels are corrected to 40-50% (0.40-0.50 U/mL) before endoscopy to prevent procedure-related bleeding 5, 2

Endoscopic Therapy

• Use combination therapy: Epinephrine injection PLUS thermal coagulation or mechanical clips for high-risk stigmata (active bleeding, visible vessel, adherent clot) 3, 4
• Never use epinephrine injection alone - it provides suboptimal efficacy and must be combined with second modality 3, 4
• Injection therapy with alcohol has shown 100% initial hemostasis and 82.6% permanent hemostasis in hemophiliacs with only 17.4% rebleeding rate 2

Common Etiologies in Hemophilia

• Duodenal ulcer is the most common cause (22-43%) of GI bleeding in hemophiliacs 7, 5, 2
• Other causes include gastritis (14%), esophagitis, Mallory-Weiss tears, and intramural hematomas 7, 5, 2
• Intramural hematoma is a rare but life-threatening manifestation with 12.2% overall mortality (23.3% in children) requiring prompt factor replacement 7

Management of Rebleeding

Second-Line Interventions

• If rebleeding occurs, attempt repeat endoscopic therapy first 3, 4
• If first-line bypassing agent fails, switch to alternative agent (rFVIIa to aPCC or vice versa) 1
• Consider transcatheter arterial embolization if endoscopic hemostasis fails, before proceeding to surgery 8

Surgical Considerations

• Delay surgery until inhibitor eradication if possible 1
• Surgery required in only 6.5% of hemophiliacs with GI bleeding when endoscopic injection therapy used 2
• Provide prophylactic bypassing agents before any invasive procedures 1

Prevention of Iatrogenic Bleeding

Procedural Precautions

• Even minor procedures like peripheral venous access may cause significant bleeding - use extreme caution 1
• Avoid central venous access unless absolutely necessary and cover with bypassing agent if required 1
• Nasogastric tube placement should be performed cautiously only after factor correction 1

Post-Acute Management

Prophylaxis Against Recurrence

• Consider prophylactic factor replacement therapy to prevent recurrent bleeding episodes, particularly after intramural hematomas 7
• Test all patients for H. pylori and provide eradication therapy if positive to reduce ulcer recurrence 3, 4
• Continue PPI therapy indefinitely if patient requires antiplatelet or anticoagulant therapy 3, 4

Risk Factors Requiring Vigilance

• Severity of hemophilia and history of retroperitoneal hemorrhage are significant risk factors for GI bleeding 5
• Factor replacement requirements correlate with bleeding severity, not etiology 5
• Mortality without treatment approaches 41%, reduced to 20% with immunosuppressive therapy in acquired hemophilia 1