Medication Summary
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. [27, 28, 29] Intravenous bolus doses in clinical trials for rFVIIa anticoagulation reversal have varied widely, 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. However, no mortality benefit has yet been demonstrated for rFVIIa or PCC over FFP; studies have shown improvement only of secondary endpoints, such as intracranial hematoma size, total volume of blood products, and time to operative intervention. [28, 29, 30, 31]
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 K1 is the only effective antidote for long-term management, but it takes several hours to reverse anticoagulation. Oral vitamin K1 has excellent bioavailability, is rapidly absorbed, and is recommended in the absence of serious or life-threatening hemorrhage. [32] Intramuscular or subcutaneous administration may cause hematoma in anticoagulated patients and offers no benefits over oral administration. Intravenous vitamin K1 has been reported to cause an anaphylactoid reaction but is the preferred route of administration for serious or life-threatening hemorrhage.
Antidotes, Other
Class Summary
Activated charcoal is empirically used to minimize systemic absorption of the toxin.
Vitamin K1 is used in the management of poisoning and overdose, in the prevention of toxic effects, and in metabolic disorders in which toxic substances accrue.
Activated charcoal (Actidose-Aqua, Char-Caps, Kerr Insta-Char)
Activated charcoal is the emergency treatment used for poisoning caused by drugs and chemicals. A network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Activated charcoal does not dissolve in water.
Administer activated charcoal to patients who present 1-2 hours postingestion or to patients in whom co-ingestants may delay gastric emptying or gut motility; minimal benefit is expected if more than 4 hours have passed since the ingestion.
Phytonadione (MEPHYTON)
Phytonadione (Vitamin K1) can overcome competitive block produced by warfarin and other, related anticoagulants. (Note that vitamin K3 [menadione] is not effective for this purpose.) The clinical effect is delayed for several hours while liver synthesis of clotting factors is initiated and plasma levels of clotting factors II, VII, IX, and X are gradually restored.
Vitamin K1 is not to be administered prophylactically; use only if evidence of anticoagulation exists. The required dose varies with the clinical situation, including the amount of anticoagulant ingested and whether it is a short-acting or long-acting anticoagulant.
Blood Components
Class Summary
Fresh frozen plasma (FFP) has been the mainstay for urgent anticoagulation reversal in patients taking vitamin K antagonists (eg, warfarin). FFP requires blood group typing and thawing before use. Unlike plasma, human prothrombin complex concentrate does not require blood group typing or thawing and is administered in a significantly lower volume than plasma. Prothrombin does have a slightly higher risk for thromboembolic (TE) events compared with plasma, particularly in patients with a history of TE events.
Fresh frozen plasma
Each unit provides all plasma proteins and clotting factors to support adequate hemostasis to treat bleeding.
Prothrombin complex concentrate, human (Kcentra)
Contains Factors II, VII, IX, X, Protein C and S. It is indicated for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist therapy in adults with acute major bleeding.
