Fixed dose PCC?

In the past, vitamin K and FFP were the mainstays of reversing warfarin, but now we have fancy new drugs like four-factor prothrombin complex concentrate (4F-PCCs).  4F-PCCs can rapidly reverse the INR of warfarin induced coagulopathy with less volume and quicker than FFP.  Many of the dosing regimens base the dose on the patient’s presenting INR and body weight, with ranges from 25-50 IU/kg.  A few problems arise with this approach, first the INR is not immediately available.  Second, 4F-PCCs are not cheap; costing up to $7,000 per patient in some cases.  Is there a fixed-dose regimen that we can give to patients on vitamin K antagonists without having to wait for the INR?

Some studies have looked at using 500 IU and 1000 IU fixed dose regimens for reversing the INR.  The 500 IU only corrected the INR in 43% of the patients, whereas the 1000 IU fixed dose study showed better clinical outcomes in 83.5% of the patients, but there is concern that the obesity epidemic in the United States will dilute the IU/kg concentration of the 4F-PCC and not be as efficacious.  Klein et al looked at using a fixed dose of 1500 IU of 4F-PCC for reversal of warfarin in 2015.  It was a relatively small sample of 38 patients on warfarin with the vast majority of them presenting with an intracranial hemorrhage.  Each patient had their INR drawn and then 1500 IU given before the result of the INR returned.  92.3% of the patients had their INR lowered to less than 2.0 after the 1500 IU of 4F-PCC and they reported no thrombotic events within the subsequent 7 days.  The presenting INR median was 3.3 (2.5-4.0) which was reduced to 1.4 (1.2-1.6) after administration of the 4F-PCC.  Additionally, this saved $40,273 dollars when compared to the typical INR and weight based dosing regimen for their patient sample.

We’ll have to figure out whether this fixed dose regimen of 1500 IU is the way to go, or should we base the dose solely on the patient’s weight and not worry about waiting on the INR.  Does waiting the extra 20 minutes for the INR lead to improved clinical outcomes?  And if we are going to start using a standard dose, is there a role for pre-hospital administration of the 4F-PCCs?

Post by: Terrance McGovern DO, MPH (@drtmcg13)

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