Anticoagulant Reversal Handbook - Page 10

8 especially in patients with an INR of > 4.0 . 4 The effect of PCC in reversing the warfarin-induced coagulopathy is so reproducible and reliable that our practice is to give the PCC and proceed to surgery , if necessary , without waiting for confirmation that the prolonged INR has been corrected .
Fresh frozen plasma versus PCC Despite the clear guideline advice to use PCC for the immediate correction of the coagulopathy , many centres continue to use fresh frozen plasma ( FFP ). FFP contains all the clotting factors but in a very dilute form . It has to be administered slowly , in large volume , has to be thawed before use , and has to be of the appropriate blood group . In contrast , PCC volume is small , can be given quickly , requires no thawing and is not blood group-specific . 1 In a recent report analysing data from two randomised trials , Refaai and colleagues showed a much higher risk of fluid overload with FFP when compared with PCC . 5 4F-PCCs have been the standard care of treatment of warfarin reversal associated with major bleeding in Europe for almost 20 years , but they were only recently licensed in the USA following the randomised trial of Sarode and colleagues that confirmed the superiority of PCC . 6 The superiority of
PCC over FFP has also been demonstrated in patients on warfarin who require emergency surgery . 7 There are some concerns around the possibility of PCC inducing thrombosis
but , in reality , this risk is small and actually no higher than the risk when using FFP . 8 Another important issue is that not all thrombotic events in PCC-treated patients are secondary to the PCC , because these patients are individuals with a high risk of thrombosis , and which is why they were on warfarin in the first place . Many of these thromboses tend to occur a week or later after PCC administration . Provided the observed bleeding is life- or limb-threatening , we believe that the optimal treatment is with intravenous vitamin K and 4F-PCC . 3 , 9
DOAC reversal The introduction of DOACs into clinical practice is rapidly changing the field and they are often preferred to warfarin due to their oral intake without any monitoring . Furthermore , DOACs have fewer drug interactions than warfarin and their short half-lives allow easier elective perioperative management . One reason for some reluctance to commence a DOAC is the lack of a reversal agent . A
“ The superiority of PCC over FPP has been demonstrated in patients on warfarin who require emergency surgery ”
specific antidote for dabigatran has been licensed but has not been used extensively or reported on . Clinical trials are ongoing with the specific factor Xa reversal agents and none of these are licensed or available for use outside of clinical trials .
While waiting for the widespread availability of the specific antidotes , a number of guidelines on the management of DOAC-related bleeding have been published . 9 , 10 Because DOACs have relatively short half-lives of 12 – 16 hours , pharmacological reversal may not always be necessary . Provision of supportive care while the levels of the anticoagulant are reducing over time will often be sufficient . The measurement of the specific concentration of the anticoagulant , if available , can be helpful , especially in confirming that the level is low . 11 Dabigatran , but not the Xa inhibitors , can www . hospitalpharmacyeurope . com