- Vitamin K antagonists (VKAs) are widely used for the primary and secondary prevention of venous and arterial thromboembolic events.
- VKAs, such as warfarin, interfere with the y-carboxylation of the calcium-active binding sites for vitamin K-dependent proteins (including coagulation factors II, VII, IX and X), resulting in the reduction of clotting factors II, VII, IX, X as well as pro-coagulation proteins C and S.
- The most common adverse reaction of warfarin is hemorrhage, accounting for approximately 29,000 emergency department visits per year.
- There are up to 10,000 cases of warfarin-associated intracranial hemorrhage (ICH) in the US annually.
- Patients on warfarin who experience head injury have a 40% higher risk of incurring ICH and a 2-fold higher risk of 30-day in-hospital mortality.
VKA-related bleeding
- Warfarin reversal strategies include: fresh frozen plasma (FFP), vitamin K, prothrombin complex concentrates (PCC): (3 Factor PCC, non-activated 4 Factor PCC and activated 4F Factor PCC)
- The prothrombin time (PT) test or International Normalized Ratio (INR), which is a standardized expression of the PT, is most commonly used to monitor VKA therapy.
- The most common target INR is 2.0–3.0 for patients on warfarin; the INR range can vary depending on the indication when on VKA therapy.
- In two pivotal clinical trials, the INR reduction target for VKA reversal was ≤1.3 at 0.5 hours after end of infusion
Multiple treatment guidelines recommend the use of 4F-PCC for urgent warfarin reversal in acute major bleeding and need for urgent surgery/invasive procedure including:
- American College of Chest Physicians (ACCP) 2012 and 2018
- American Society of Hematology (ASH) 2018
- American College of Surgeons (ACS) 2018
- American College of Cardiology Consensus Paper
- American College of Emergency Physicians (ACEP)/Annals of Emergency Medicine 2019
- Neurocritical Care Society/Society of Critical Care Medicine 2015
- American Society of Gastrointestinal Endoscopy ASGE 2016
- Thrombosis Canada Direct Oral Anticoagulants (DOACs): Management of Bleeding
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