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