Should anticoagulation be held in a patient with Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) who develops a Gastrointestinal (GI) bleed?

Management of Anticoagulation in DVT/PE Patients with GI Bleeding

Anticoagulation should generally be resumed within 90 days after surviving a major GI bleed in patients with DVT and PE, rather than permanently discontinuing it, provided the patient is not at high risk for recurrent bleeding and requires long-term anticoagulation. 1

Immediate Management During Active GI Bleeding

Temporary Cessation of Anticoagulation

• Anticoagulation should be held during active, hemodynamically significant GI bleeding until hemostasis is achieved 2, 3
• For life-threatening bleeding on heparin (UFH or LMWH), protamine administration should be considered in addition to cessation of heparin therapy, though protamine is most effective for UFH rather than LMWH 1
• For patients on warfarin with life-threatening GI bleeding, 4-factor prothrombin complex concentrate (4F-PCC) is preferred over fresh frozen plasma 2, 3
• For patients on DOACs with GI bleeding, reversal agents (idarucizumab for dabigatran, andexanet alfa for rivaroxaban/apixaban) are generally not recommended unless bleeding is truly life-threatening 2, 3

Critical Distinction: Major vs Minor Bleeding

• Minor GI bleeding that does not cause hemodynamic compromise does not necessarily require anticoagulation cessation 1, 4
• The decision hinges on hemodynamic stability: if stable, continuation may be appropriate with close monitoring 4

Resumption of Anticoagulation After GI Bleeding

Evidence Supporting Resumption

The most compelling evidence comes from the 2018 ASH guidelines showing that resuming anticoagulation after major bleeding (including GI bleeding) is associated with:

• 62% reduction in all-cause mortality (RR 0.62,95% CI 0.43-0.89) - translating to 165 fewer deaths per 1000 patients 1
• 55% reduction in thromboembolism risk (RR 0.45,95% CI 0.25-0.83) - translating to 58 fewer events per 1000 patients 1
• Possible reduction in PE (RR 0.35) and VTE recurrence (RR 0.58), though with wider confidence intervals 1

Timing of Resumption

• Anticoagulation should be resumed within 90 days after the major bleeding episode 1
• The specific timing within this 90-day window depends on:
  • Source of bleeding identified and treated 1, 2
  • Hemodynamic stability achieved 4
  • Bleeding risk reassessed as not prohibitively high 1

Patient Selection for Resumption

This recommendation specifically applies to patients who:

• Require long-term or indefinite anticoagulation (moderate to high risk for recurrent VTE) 1
• Are not at high risk for recurrent bleeding 1
• Are willing to continue anticoagulation therapy 1

Risk Stratification for Decision-Making

High-Risk Patients Requiring Extended Anticoagulation

These patients have the strongest indication for resumption:

• Unprovoked proximal DVT or PE 1
• Second unprovoked VTE 1
• Active cancer-associated thrombosis 1
• DVT/PE provoked by chronic persistent risk factors (e.g., inflammatory bowel disease, autoimmune disease) 1

Lower-Risk Patients Where Discontinuation May Be Considered

• First isolated distal (calf) DVT that was unprovoked 1, 5
• VTE provoked by transient, reversible risk factors (surgery, trauma) that have resolved 1, 5
• Patients with prohibitively high bleeding risk 1

Practical Algorithm for Management

Step 1: During Active GI Bleeding

• Hold anticoagulation if hemodynamically unstable or bleeding is severe 2, 3
• Administer reversal agents only for life-threatening bleeding: 4F-PCC for warfarin, specific reversal agents for DOACs only in extremis 2, 3
• Achieve endoscopic hemostasis 2
• Identify and treat underlying GI pathology 4

Step 2: Assess VTE Recurrence Risk

• High recurrence risk (annual risk >5%): unprovoked VTE, cancer-associated VTE, recurrent VTE, chronic risk factors 1, 5
• Low recurrence risk (annual risk <1%): surgery-provoked VTE, isolated distal DVT 1, 5

Step 3: Assess Bleeding Recurrence Risk

• High bleeding risk factors include: advanced age >70 years, previous bleeding history, concomitant antiplatelet agents or NSAIDs, uncontrolled hypertension 4
• Modifiable factors: verify INR therapeutic range (2.0-3.0) if using warfarin, avoid over-anticoagulation 4

Step 4: Decision Point

• If high VTE recurrence risk + low-to-moderate bleeding risk: Resume anticoagulation within 90 days 1
• If high VTE recurrence risk + high bleeding risk: Consider resumption with close monitoring or reduced-intensity anticoagulation 1
• If low VTE recurrence risk: May discontinue after completing 3-6 months primary treatment 1, 5

Choice of Anticoagulant Upon Resumption

Preferred Agents

• DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) are generally preferred over warfarin due to safety profile and convenience 4
• For standard-dose vs reduced-dose DOACs after primary treatment: either option is acceptable (rivaroxaban 10 mg daily or apixaban 2.5 mg twice daily for reduced dosing) 1

Special Populations

• Cancer-associated thrombosis: LMWH or DOACs (apixaban, rivaroxaban, edoxaban) are preferred, with caution for GI or urothelial cancers where LMWH may be safer 1, 6
• Patients with breakthrough VTE on warfarin: Consider switching to LMWH 1

Common Pitfalls to Avoid

• Do not permanently discontinue anticoagulation based solely on a single GI bleeding episode - the mortality benefit of resumption outweighs bleeding risk in most patients requiring long-term anticoagulation 1
• Do not routinely use reversal agents for non-life-threatening GI bleeding - cessation alone is usually sufficient 1, 2
• Do not resume anticoagulation without identifying and addressing the GI bleeding source 4, 2
• Do not forget to reassess the indication for anticoagulation periodically (at least annually) once resumed 1
• Avoid concomitant antiplatelet agents (especially aspirin for primary prevention) unless absolutely necessary - significantly increases bleeding risk 1, 4

Monitoring After Resumption

• Verify therapeutic anticoagulation levels: INR 2.0-3.0 for warfarin 1, 4
• Monitor renal function approximately every 3 months for DOAC dosing adjustments 1
• Reassess bleeding and thrombosis risk at periodic intervals (annually minimum) 1
• Surveillance for new bleeding risk factors that may modify the decision to continue 4