In this episode, I’ll discuss why warfarin needs overlap with another anticoagulant when treating VTE.
The CHEST guidelines state:
It is now standard practice to start anticoagulant treatment after VTE with a heparin (unfractionated or low molecular weight) together with a VKA, overlap the two drugs for at least 5 days, and stop the heparin only after the INR exceeds 2.0 for > 2 consecutive days.
Understanding the reasoning for this recommendation can help if you need to convince a provider of the need for such overlap.
Warfarin inhibits the vitamin K dependent coagulation and anticoagulation factors These coagulation factors are II, VII, IX, X and the anticoagulation factors are Protein C and Protein S.
The half-lives of these factors in ascending order are as follows:
VII = 6 hours
Protein C = 8 hours
IX = 24 hours
Protein S = 30 hours
X = 48 hours
II = 60 hours
The most important factors to inhibit for warfarin’s clinical efficacy are also the ones with the longest half-life (II and X) although the INR will rise more quickly when therapy starts in response to inhibition of the less important factors with shorter half-lives.
This translates to the warfarin’s clinical efficacy not appearing for a minimum of 3 days while the INR may increase faster than that.
The recommended period of overlap is intended to provide for full anticoagulation from heparin or LMWH while the clinical effects of warfarin start to develop.
However, there is an additional effect of starting warfarin that is important to consider in patients with an active clot, and that is warfarin’s inhibition of the anticoagulation factors protein C and S.
Proteins C and S are responsible for inhibiting activated factors VIII and V. Because protein C and S have short half-lives, their levels drop rapidly when warfarin is started but before factors II and X are reduced. This results in a temporary procoagulant period when warfarin is started. Providing overlap with another anticoagulant protects from this procoagulant effect.
It is important to remember this overlap strategy is only clinically relevant if there is already an ongoing thromboembolism such as a DVT or PE. When there is not an existing thromboembolic event, such as in atrial fibrillation, the initial procoagulant period is ignored and warfarin is started without overlap.
Members of my Hospital Pharmacy Academy have access to practical training from a pharmacist’s point of view on Inpatient Warfarin Initiation. This is in addition to hundreds of other trainings and resources to help in your practice. To get immediate access, go to pharmacyjoe.com/academy.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.