What is the role of medications in the treatment of warfarin and superwarfarin toxicity?

Updated: Jan 19, 2018
  • Author: Kent R Olson, MD, FACEP; Chief Editor: David Vearrier, MD, MPH  more...
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Answer

For prothrombin complex concentrate (PCC), as a general guideline, a dosage of 50-100 units/kg IV at 12-hour intervals is recommended. The lower range is recommended for joint or mucous membrane bleeding. For soft tissue bleeding, 100 units/kg every 12 hours is recommended. For severe hemorrhage (eg, central nervous system [CNS] bleeding), 100 units/kg every 12 hours is recommended, although a more frequent dosing interval (ie, 6 h) may be indicated until clear clinical improvement is achieved.

Recombinant factor VIIa (rFVIIa; NovoSeven) has been shown to correct the international normalized ratio (INR) within hours. [22, 23, 24] Intravenous bolus doses in clinical trials for rFVIIa anticoagulation reversal have varied widley, from 5-320 mcg/kg. Mean doses ranged from 16.3-87.35 mcg/kg.

The potential benefits of rFVIIa or PCC over fresh frozen plasma (FFP) include faster administration (because rFVIIa and PCC do not have to be thawed), smaller infusion volumes, and decreased risk of transfusion-associated adverse reactions. Studies have shown improvement only of secondary endpoints, such as intracranial hematoma size, total volume of blood products, and time to operative intervention. [23, 24, 25, 26]  However, no mortality benefit has yet been demonstrated for rFVIIa or PCC over FFP.

FFP may be administered instead of PCC or rFVIIa if those therapies are unavailable. An FFP volume of 15 mL/kg (approximately 4 units in a 70 kg adult) is typically sufficient to reverse coagulopathy. Packed red blood cells may be transfused as needed for blood loss. 

Vitamin K 1 is the only effective antidote for long-term management, but it takes several hours to reverse anticoagulation. Oral vitamin K 1 has excellent bioavailability, is rapidly absorbed, and is recommended in the absence of serious or life-threatening hemorrhage. [27] Intramuscular or subcutaneous administration may cause hematoma in anticoagulated patients and offers no benefits over oral administration. Intravenous vitamin K 1 has been reported to cause an anaphylactoid reaction but is the preferred route of administration for serious or life-threatening hemorrhage.


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