What is the role of coumarins in deep venous thrombosis (DVT) prophylaxis for patients undergoing orthopedic surgery?

Updated: Jul 25, 2019
  • Author: David A Forsh, MD; Chief Editor: Vinod K Panchbhavi, MD, FACS  more...
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Answer

Answer

Coumarins are a class of oral anticoagulant drugs, which act as antagonists to vitamin K. The mechanism of action is to interfere with the interaction between vitamin K and coagulation factors II, VII, IX, and X. Vitamin K acts as a cofactor at these levels. Coumarins produce their anticoagulant effect by inhibiting the carboxylation necessary for biologic activity.

Warfarin is a mixture of two isomers, the R and S forms, in roughly equal proportions. This agent is absorbed rapidly from the gastrointestinal (GI) tract and bound to plasma proteins. Although it has high bioavailability, warfarin requires 36-72 hours to reach a stable loading dose. The dose response in patients taking warfarin is variable, and it is influenced by various genetic and environmental factors. In addition, numerous drug interactions and disease states may affect its pharmacokinetics. Warfarin, therefore, requires continuous laboratory monitoring.

The effectiveness of warfarin anticoagulation is measured by determining the prothrombin time (PT) or protime against a standard control. The use of the international normalized ratio (INR) has supplanted the PT for hospital use. INR uses a standardized PT, which allows for comparisons between hospitals and laboratories.

For DVT prophylaxis, the optimal INR is between 2 and 3, with a target of 2.5. When used for DVT prophylaxis after THR, warfarin reduces total DVT by 60% and proximal DVT by 70%. Disadvantages of warfarin use include its long onset of action, the necessity to monitor INR values frequently to obtain a stable dosage, the long half-life that may require vitamin K reversal in incidents of hemorrhage, frequent drug and dietary interaction, and variable patient response. Hemorrhagic complications are reported in up to 3-5% of patients on warfarin prophylaxis.

If adjusted-dose warfarin is to be used, it is started the night before surgery and continued postoperatively during the discharge period. INR target levels are not usually reached until postoperative day 3.


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