Bridging Therapy : Rationale

Bridging Theraphy & Rationale

• Bridge therapy  refers to temporary use of intravenous unfractionated heparin or LMWH for a patient on long-term anticoagulation.

• Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of thromboembolism with the risk of bleeding.

• In many cases, warfarin is initiated in hospitals due to presence of active clot. In this situation, warfarin is usually started in conjunction with heparin. This is because: 

1.   The anticoagulant effect of warfarin does not occur for approximately 2-3 days.

2.   Initial period of the treatment with warfarin may be associated with a procoagulant state; heparin provides some protection from the risk related to this.

What is Procoagulant State?

• The anticoagulant effect of warfarin results from the inhibition of the cyclic interconversion of vitamin K in the liver.

• Warfarin, similar in structure to vitamin K, interferes with the cyclic restoration of reduced levels of vitamin K. Hence, warfarin indirectly reduces the synthesis of these clotting factors.

• Warfarin also has simultaneous procoagulant effect, caused by blocking protein C and S.

• Since protein C and S are anticoagulants, a rapid depletion of these proteins leads to a transient hypercoagulable state in first one to two days of warfarin therapy.

Onset of Anticoagulant Effect of Warfarin

• An anticoagulation effect generally occurs within 24 hours after warfarin administration. However the full anticoagulant effect of warfarin does not occur until two to three days of drug administration

• Anticoagulant effects of warfarin are delayed for several days after dosing changes and therapy initiation. This is because of the variable half-lives of previously formed circulating clotting factors.

• During the first few days of warfarin therapy, prolongation of the PT/INR mainly reflects depression of factor VII, which has the shortest half-life (four to six hours); however, other vitamin K-dependent factors (eg, factors II [prothrombin], IX, and X) have longer half-lives and are not fully depleted for two to three days.

• Thus, for patients with a very high thromboembolic risk, it may be necessary to overlap ("bridge") warfarin with another anticoagulant such as unfractionated or low molecular weight heparin during initiation of warfarin therapy.

Reference: 

1. http://www.aafp.org/afp/2013/0415/p556.html
2. http://www.bpac.org.nz/resources/campaign/inr/inr_poem.asp?page=3
3. https://www.drugs.com/pro/warfarin.html