Is a person at high risk of both stroke and bleeding when being bridged with heparin (unfractionated heparin) or low molecular weight heparin (LMWH) during the initiation of warfarin (coumarin) therapy?

Bridging Anticoagulation: Dual Risk of Stroke and Bleeding

Yes, patients being bridged when starting warfarin therapy face significantly elevated bleeding risk (2-3 fold increase) without meaningful reduction in stroke risk, making bridging inappropriate for most patients with nonvalvular atrial fibrillation. 1, 2, 3

The Evidence Against Routine Bridging

The landmark BRIDGE trial definitively demonstrated that bridging therapy increases major bleeding risk threefold (3.2% vs 1.3%; OR=3.60) while providing no thromboembolic protection (0.3% vs 0.4% arterial thromboembolism). 2, 4 This finding has fundamentally changed clinical practice, with the American College of Cardiology now recommending against bridging for patients with nonvalvular atrial fibrillation at low to moderate thromboembolic risk. 2

Bleeding Risk Profile

• Major bleeding occurs in 3.2% of bridged patients compared to 1.3% of non-bridged patients during warfarin initiation. 2, 4
• Multiple studies consistently show a 2-3 fold increase in bleeding complications with heparin bridging across different patient populations. 3
• The FDA warns that hemorrhage can occur at virtually any site in patients receiving heparin, with fatal hemorrhages documented, particularly in patients over 60 years of age. 5
• German registry data revealed major hemorrhage rates of 2.7% with bridging versus 0.5% without bridging (p=0.01), with no reduction in thromboembolism. 1

Stroke Risk During Bridging

• The actual stroke risk during brief warfarin interruption (≤5 days) is remarkably low at 0.7% (95% CI: 0.3%-1.4%) in patients not receiving bridging therapy. 6
• No reduction in ischemic events occurs with bridging therapy compared to no bridging in nonvalvular atrial fibrillation patients. 1
• The RE-LY trial showed bridging of dabigatran with LMWH resulted in higher major hemorrhage (6.5% vs 1.8%, p<0.001) with no difference in thrombosis rates. 1

Who Actually Requires Bridging

Bridging therapy should be reserved exclusively for patients at very high thromboembolic risk, as the bleeding risk outweighs benefits in all other scenarios. 1

High-Risk Patients Requiring Bridging

• Patients with mechanical heart valves (particularly older-generation or mitral position valves) undergoing procedures requiring warfarin interruption. 1, 2
• Recent stroke or TIA within 3 months. 1, 2
• CHADS₂ score of 5 or 6 (or CHA₂DS₂-VASc score ≥7). 1, 2
• History of perioperative stroke. 2, 4
• Rheumatic valve disease. 1

Patients Who Should NOT Be Bridged

• Nonvalvular atrial fibrillation patients with CHA₂DS₂-VASc score <7 or CHADS₂ score <5. 2
• Patients undergoing brief warfarin interruption (≤5 days) for minor procedures. 6
• Patients on DOACs (direct oral anticoagulants) requiring temporary interruption, as the pharmacokinetic properties of these agents obviate bridging need. 3

Critical Pitfalls to Avoid

The most common and dangerous error is bridging average-risk atrial fibrillation patients, which increases bleeding without providing thromboembolic protection. 2, 4

Additional Hazards

• Combining bridging anticoagulation with antiplatelet therapy (aspirin or clopidogrel) increases bleeding risk by more than 50% (HR 1.50-1.84). 4
• The combination of warfarin plus aspirin increases major bleeding to 4.95% per year compared to 1.5% with warfarin alone (p=0.004). 1
• Symptomatic hemorrhagic transformation after cardioembolic stroke occurs significantly more frequently with enoxaparin bridging (10%, p=0.003). 7
• Premature discontinuation of heparin/LMWH before INR reaches therapeutic range (2.0-3.0) on two consecutive measurements leaves patients unprotected. 2, 8

Proper Bridging Protocol (When Indicated)

For the rare high-risk patient requiring bridging, LMWH is preferred over unfractionated heparin due to outpatient administration capability and no monitoring requirements. 1, 8

LMWH Bridging Regimen

• Enoxaparin 1 mg/kg twice daily or 1.5 mg/kg once daily, or dalteparin 200 IU/kg once daily. 8
• Stop warfarin 5 days before procedure. 8
• Start LMWH 3 days before procedure (36-48 hours after last warfarin dose). 1, 9
• Stop LMWH 24 hours before procedure. 1, 8
• Resume warfarin evening of procedure at usual maintenance dose. 8, 9
• Resume LMWH 24 hours postoperatively (or when hemostasis secured). 1, 8, 9
• Continue LMWH until INR reaches 2.0-3.0 on two separate measurements. 1, 8, 9

Special Considerations

• In patients with severe renal insufficiency (CrCl <30 mL/min), unfractionated heparin may be necessary as LMWH accumulates. 1, 8
• For high-bleeding-risk procedures, resume warfarin postoperatively but delay or omit postprocedural LMWH. 9
• The FDA mandates continuing heparin until INR returns to therapeutic levels to ensure continuous anticoagulation. 5