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Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy
  1. Carmen Sobrino Jiménez1,
  2. José Antonio Romero-Garrido1,
  3. Ángeles García-Martín1,
  4. Manuel Quintana-Díaz2,
  5. Carlos Jiménez-Vicente1,
  6. Luis González-Del Valle1,
  7. Alicia Herrero Ambrosio1,
  8. Juana Benedí-González3
  1. 1 Department of Hospital Pharmacy, Hospital Universitario La Paz, Madrid, Spain
  2. 2 Intensive Care Unit, Hospital Universitario La Paz, Madrid, Spain
  3. 3 Department of Pharmacology, Universidad Complutense de Madrid, Madrid, Spain
  1. Correspondence to Dr Carmen Sobrino Jiménez, Pharmacy, Hospital Universitario La Paz, Madrid 28046, Spain; carmen.sobrino{at}


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.

  • bleeding disorders & coagulopathies
  • accident & emergency medicine
  • anticoagulation
  • surgery
  • adverse effects
  • therapeutic drug monitoring
  • intensive & critical care
  • clinical pharmacy

Data availability statement

Data are available upon reasonable request.

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