Clinical Conundrum:
Do direct oral anticoagulants (DOACs) require overlapping or “bridging” with low molecular weight heparin (example: enoxaparin) or unfractionated heparin upon initiation of therapy?
Background:
Warfarin has a half-life of 36-48 hours and requires 5-6 days of therapy before a patient achieves a therapeutic INR (2-3). In the first few days of therapy, decreases in protein C and S (natural anticoagulants) results in a prothrombotic state.
Subcutaneous administration of LMWH provides peak anti-FXa activity within 3-5 hours and a half-life of 5-7 hours.
Typically, IV heparin protocols do not provide immediate therapeutic effects. It has been found in studies that it can take up to 15 hours for to reach a patient's first therapeutic lab level.
DOACs have a rapid onset of action, with peak plasma levels occurring within 2-4 hours depending on the agent selected and a half-life of 8-12 hours.
Answer:
Warfarin must be overlapped with LMWH or UFH for 3- 5 days and at times up to 7 days to provide sufficient anticoagulation upon therapy initiation based on pharmacokinetic parameters.
DOACs do not need to be overlapped with LMWH upon therapy initiation due to the rapid onset of action.
Similarly, due to the short half-life, DOACs do not need to be “bridged” peri-procedurally with LMWH or UFH when therapy is interupted.
Written by: Hanan Khadra, Doctor of Pharmacy Candidate, Class of 2021
Reviewed by: Joanne Routsolias, ED/Toxicology Specialty PharmD
References:
Kahlon P, Nabi S, Arshad A, Jabbar A, Haythem A. Warfarin Dosing and Time Required to Reach Therapeutic International Normalized Ratio in Patients with Hypercoagulable Conditions. Hiperkoagülabilite Durumları Olan Hastalarda Terapötik Uluslararası Düzeltme Oranına Ulaşmak için Gerekli Warfarin Doz ve Süresi. Turk J Haematol. 2016;33(4):299-303. doi:10.4274/tjh.2015.0271
Clinical Pharmacology powered by ClinicalKey [online database]. https://www-clinicalkey-com.proxy.cc.uic.edu/pharmacology/monograph/221?sec=monphar. Accessed October 24, 2020.
Almarshad F, Alaklabi A, Bakhsh E, Pathan A, Almegren M. Use of direct oral anticoagulants in daily practice. Am J Blood Res. 2018;8(4):57-72. Published 2018 Dec 10.
Hosch LM, Breedlove EY, Scono LE, Knoderer CA. Evaluation of an Unfractionated Heparin Pharmacy Dosing Protocol for the Treatment of Venous Thromboembolism in Nonobese, Obese, and Severely Obese Patients. Ann Pharmacother. 2017 Sep;51(9):768-773. doi: 10.1177/1060028017709819. Epub 2017 May 16. PMID: 28511582.