Key result
Fixed-dose 4F-PCC achieves target INR in ~70% of urgent VKA reversals.
Why the study?
Clinical data evaluating the efficacy and safety of a fixed-dose four-factor prothrombin complex concentrate strategy for vitamin K antagonist reversal were limited.
Does a fixed-dose strategy of 4F-PCC effectively correct INR in adult patients requiring VKA reversal?
Cohort (n=145)
No
Does a fixed-dose strategy of 4F-PCC effectively correct INR in adult patients requiring VKA reversal?
p-value: p=<0.0001
A fixed-dose strategy of 4F-PCC (initial 1000 IU) effectively corrects INR and restores hemostasis in patients requiring VKA reversal, with a low rate of thromboembolic complications.
May support fixed-dose 4F-PCC for urgent VKA reversal; extends low-certainty observational evidence but leaves open need for RCTs.
OBJECTIVES: Early reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25-50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy. METHODS: This was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients. RESULTS: A total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p<0.0001). In one case, a thromboembolic complication was possibly related to 4F-PCC. The aPTT ratio target was reached in 113 (77.9%) patients (p<0.0001), and 79 of the 106 (74.5%) patients reversed for bleeding achieved haemostatic effectiveness. CONCLUSIONS: After 4F-PCC, the majority of patients achieved the target INR, meaning 4F-PCC is a useful modality for rapid INR reduction. The safety profile may be considered acceptable. Fixed-dose 4F-PCC was able to restore haemostasis rapidly while minimising the risk of adverse events and optimising available resources.
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Jiménez et al. (2020) conducted a cohort in Vitamin K antagonist reversal (n=145). Four-factor prothrombin complex concentrate (4F-PCC) was evaluated on INR correction (INR ≤1.5 in the first INR draw after 4F-PCC administration) (p=<0.0001). A fixed-dose strategy of four-factor prothrombin complex concentrate successfully achieved the target INR of ≤1.5 in 70.3% of patients requiring urgent vitamin K antagonist reversal.
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