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Oral Anticoagulation Reversal Learning Zone

Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal

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Last updated:12th Mar 2020
Published:12th Feb 2020
Vitamin K antagonists (VKAs), most commonly warfarin, are a widely prescribed class of drug used as a therapeutic or prophylactic treatment against thrombotic diseases. Reversal of VKAs is necessary in an emergency setting as a result of acute haemorrhage or as preparation for surgery or invasive procedures.

This reversal has typically been accomplished via administration of plasma, which itself can cause significant adverse events. Four-factor prothrombin complex concentrate (4F-PCC) is a lyophilised non-activated concentrate of vitamin K-dependent clotting factors (brands include Beriplex, Octaplex and Kcentra) and has been demonstrated to be an effective alternative to plasma. This study compared data from two phase IIIb randomised controlled trials to assess the relative risk of volume overload occurring as a result of plasma versus 4F-PCC administration. Volume overload is an excess of fluid in the intravascular space, and can cause cardiac failure, potentially manifesting as pulmonary oedema, ascites, peripheral oedema or a pleural effusion.

The study examined 388 adult patients who were on VKAs with an international normalised ratio (INR) of ≥2 and presented with either an acute major bleed, or required emergency surgery or an invasive procedure. The patients were randomised to receive either a single initial infusion of plasma or 4F-PCC for the purpose of VKA reversal. The median volume of plasma administered was approximately nine times that of 4F-PCC due to the nature of the infusion. The multivariate analysis of the data demonstrated the significant predictors for overload as either a history of renal disease, prior diagnosis of congestive heart failure or the use of plasma over 4F-PCC.

Given the widespread use of VKAs, the requirement for urgent reversal is a regular occurrence; the findings from this study suggest that 4F-PCC should be considered as a first-line treatment, particularly where there is pre-existing congestive heart failure and/or renal disease.