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Monday, August 29, 2016

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

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