Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal
Condition: Acute Bleeding on Long-Term Anticoagulation Therapy; Hemorrhage; Significant Bleeding in Patients With a Coagulopathy (Prolonged Thrombin Time); Urgent Reversal of Vitamin K Antagonist (VKA) Anticoagulation
MeSH terms: Hemorrhage
Intervention: 4-factor prothrombin complex concentrate (4FPCC)
Intervention description: 4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.
Intervention MeSH terms: Thrombin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: For adults on long-term warfarin therapy who present to the ED with emergent bleeding, or who are in need of urgent invasive surgical procedures: the exposure of interest will be fixed vs. variable dose 4FPCC, to which eligible patients will be randomly assigned in a 1:1 ratio.
Masking: None (Open Label)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Maximum age: 125 Years
Healthy volunteers: No

Summary:

      The goal of this study is to determine if a fixed dose of 4-factor prothrombin complex
      concentrate (4FPCC) is as effective as the current standard of care. 4FPCC is used to reverse
      the effects of warfarin when a patient has emergent bleeding. The investigators hope that
      this study will help doctors treat patients quicker in the future. In addition, it may be
      cheaper for patients and hospitals. This is the same medication the doctor would use to
      reverse warfarin's effects, but at a lower dose.

      Hypothesis: A fixed dose of 4FPCC will be comparable to FDA-approved variable dosing for
      reversal of warfarin-induced anticoagulation (defined as an international normalized ratio
      [INR] ≤ 1.5) in patients with an INR ≥2 experiencing an emergent bleed or requiring emergent
      surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic anticoagulation with warfarin and initial INR ≥2

          -  Emergent bleeding (i.e. intracranial hemorrhage, gastrointestinal hemorrhage, urgent
             invasive procedures, etc.) or urgent surgery requiring reversal of INR to ≤1.5

        Exclusion Criteria:

          -  Younger than 18 years of age

          -  History of heparin-induced thrombocytopenia (HIT)

          -  Patients without initial or post-administration INR readings

          -  Patients with an initial INR <2

          -  Pregnant patients

          -  Prisoners