From the Guidelines
Warfarin and low molecular weight heparin (LMWH) should be combined in patients with high thrombotic risk, such as those with a prosthetic metal heart valve in mitral position, atrial fibrillation with prosthetic heart valve or mitral stenosis, or less than 3 months after venous thromboembolism, to ensure immediate and continuous anticoagulation while waiting for warfarin to reach its full therapeutic effect. This approach is supported by the British Society of Gastroenterology guidelines, which recommend considering low molecular weight heparin therapy at 48 hours after hemorrhage in patients with high thrombotic risk 1. The combination of warfarin and LMWH is necessary because warfarin has a delayed onset of action, typically 3-5 days, due to its mechanism of inhibiting vitamin K-dependent clotting factor synthesis. LMWH provides immediate anticoagulation by inhibiting factor Xa, bridging the gap until warfarin becomes effective. Key points to consider when combining warfarin and LMWH include:
- Starting with LMWH (e.g., enoxaparin 1 mg/kg twice daily) and warfarin (typically 5 mg daily) simultaneously
- Continuing LMWH for at least 5 days and until the INR is ≥2.0 for two consecutive days
- Discontinuing LMWH and continuing warfarin alone, adjusting the dose to maintain an INR of 2.0-3.0
- Monitoring the patient's INR regularly, typically daily or every other day during initiation, and being aware of potential bleeding risks associated with dual anticoagulation therapy. It is also important to note that the use of LMWH has been shown to be superior to unfractionated heparin in reducing mortality and the risk of major bleeding during initial therapy for deep vein thrombosis (DVT) 1. Additionally, the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes recommends the use of LMWH, such as enoxaparin, in patients with impaired renal function 1.
From the Research
Rationale for Combining Warfarin and Low Molecular Weight Heparin (LMWH)
- The combination of Warfarin and LMWH is often used as a bridging therapy during temporary interruptions of Warfarin treatment, despite a lack of evidence showing its benefit 2.
- Studies have shown that LMWH can be used safely and effectively in place of unfractionated heparin for acute treatment at the onset of atrial fibrillation and during early cardioversion 3.
- In patients with cancer and venous thromboembolism, LMWH may be superior to Warfarin for secondary prophylaxis, with a lower risk of major bleeding and recurrent venous thromboembolism 4.
Indications for Combining Warfarin and LMWH
- Mechanical heart valve prostheses: LMWH bridging is often used in patients with mechanical heart valves who require temporary interruption of Warfarin therapy 2.
- Atrial fibrillation: LMWH can be used as a bridging therapy during cardioversion, especially in patients with a high risk of thromboembolic complications 3.
- Venous thromboembolism: LMWH may be used as a bridging therapy during treatment of venous thromboembolism, especially in patients with cancer 4.
Safety and Efficacy of Combining Warfarin and LMWH
- The safety and efficacy of combining Warfarin and LMWH have been evaluated in several studies, with mixed results 2, 5, 4, 6.
- A study found that LMWH bridging was associated with a higher rate of thrombotic events overall, but the total risk of any complication did not differ significantly between bridging and non-bridging groups 2.
- Another study found that LMWH had a significantly better safety profile than unfractionated heparin in the prevention of thromboembolism in general surgery 5.