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Oral Anticoagulation Reversal Learning Zone

Emergency reversal of vitamin K antagonists: addressing all the factors

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Last updated:12th Mar 2020
Published:12th Feb 2020
This retrospective review compared the administration of four-factor prothrombin complex concentrate (4F-PCC) with a previous departmental protocol of three-factor prothrombin complex concentrate (3F-PCC) and activated factor VII (rVIIA). There are limitations to the study, but the findings suggest that both provide adequate early reversal. 3F-PCC+rVIIA demonstrated a more potent decrease in INR which was associated with a much higher rate of thrombotic complications.

Treating traumatic haemorrhage in the presence of anticoagulation remains a balancing act between achieving haemostasis and avoiding thrombotic events. This study examines traumatic bleeding in patients on warfarin, as it remains the most commonly used oral anticoagulant. Citing a lack of direct comparisons between forms of prothrombin complex concentrate, the authors sought to determine what effect their change of reversal protocol from 3F-PCC+rVIIA to 4FPCC in haemorrhage had engendered. From 2011-2014 they used 3F-PCC+rVIIA, and from early 2014 they used 4F-PCC alone.

All patients taking warfarin who presented with a traumatic injury and required reversal of their warfarin were reviewed. The pharmacy records were tracked and cross-matched to hospital records. Various exclusion criteria meant there were 87 patients identified; 53 treated with 3F-PCC+rVIIA, and 34 treated with 4F-PCC.

The demographics, indications for reversal and injury patterns showed no significant differences between the two groups; intracranial haemorrhage was the most common reason requiring reversal. Pre-treatment INR values were similar, both were effective at bringing INR under 1.5 immediately. The median INR with 3F-PCC+rVIIA was significantly lower (0.75 [range 0.69-1.00]) than for 4F-PCC (1.28 [range 1.13-1.36] p=<0.001). Other adjuncts were also similar in their frequency of use, including vitamin K and plasma.

There was no difference in length of hospital stay between groups. A non-significant increase in mortality was observed: 17% (n=9) of the 3F-PCC+rVIIA treated group died versus 2.9% (n=1) of the group treated with 4F-PCC (p=0.08). New deep vein thrombosis (DVT) was detected in 12 of 53 3F-PCC+rVIIA patients, which was significantly higher than the single DVT detected in the 4F-PCC group (n=34).

The authors acknowledge the potential for selection bias and note that the increase in mortality is likely to be multifactorial; the early days of PCC administration may have resulted in clinicians using it as a ‘last resort’. With time and familiarity, 4F-PCC has become more quickly and widely used. They also suggest that 3F-PCC may have a more potent effect due to its use with activated clotting factors, and its lack of anticoagulant enzymes.

This study suggests that the complication rate from 4F-PCC is better than 3F-PCC+rVIIA, however, it is worth noting that due to an enhanced pro-coagulant effect, there may be a sub-group of patients that would benefit from 3F-PCC+rVIIA.