Other studies have found that PCCs achieved a significantly more rapid and complete INR reversal and correction than FFP, due to intrinsic properties as well as faster preparation because there is no need for thawing and quicker infusion rates. PCCs also have been shown to have fewer complications related to fluid overload.

The volume of PCC needed to reverse anticoagulation is far less than the volume of FFP that is needed (typically only about 5%), which decreases the risk of fluid overload. Furthermore, infusion of FFP has been known to increase the risk of TRALI, a major cause of mortality associated with transfusion. No incidents of TRALI following administration of PCCs have been reported. While some clinicians continue to use FFP because of the lower cost per unit, larger volumes of FFP are needed for effective anticoagulant reversal, resulting in an overall cost of FFP administration that is similar to that of PCCs.²

Suggested dosing schemes include using a dose of 500 U or 8.8 U/kg may be optimal for emergent warfarin reversal in patients with an INR less than 5, with adjustment of this dose for those with higher INR values.

Recombinant activated factor VII has been proposed as an alternative agent for warfarin reversal. Bolus infusions of this agent in doses ranging from 10 to 90 mcg/kg rapidly reversed warfarin toxicity accompanied by significant bleeding.

While optimal dosing has yet to be established, the short (3-hour) half-life of recombinant activated factor VII may require multiple doses if longer hemostasis is indicated, which could increase the risk of thrombosis.¹

Unfractionated heparin binds to antithrombin III to inhibit multiple steps in the extrinsic and common coagulation pathways. Unfractionated heparin must be given parenterally and its anticoagulation effect can be monitored using the activated partial thromboplastin time, which for most purposes is 1.5 to 2.5 times the “normal” value. Unfractionated heparin administration should be stopped immediately if bleeding develops.

The anticoagulant effect of heparin can last up to 3 hours. Observation is appropriate in less severe cases with serial aPTT levels used to determine when to resume heparin therapy.

Protamine can reverse the anticoagulant effect of heparin in major bleeding complications; 1 mg intravenous protamine will neutralize 100 units of heparin administered in the previous 4 hours.

However, great care should be given with protamine administration, as 0.2% of patients receiving protamine develop anaphylaxis, which has a mortality rate of 30%.3 The risk of severe adverse reactions to protamine can be minimized by administering this reversal agent slowly.