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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. 1Department of Hospital Pharmacy, Hospital Universitario La Paz, Madrid, Spain
  2. 2Intensive Care Unit, Hospital Universitario La Paz, Madrid, Spain
  3. 3Department 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}salud.madrid.org

Abstract

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
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