Initiation of a fixed-dose four-factor prothrombin complex concentrate protocol

J Thromb Thrombolysis. 2020 Jul;50(1):217-220. doi: 10.1007/s11239-019-01984-w.


Patients who require urgent warfarin reversal often receive four-factor prothrombin complex concentrate (4F-PCC), which is traditionally dosed according to weight and initial INR. Our institution implemented a fixed-dose 4F-PCC strategy, using an initial dose of 1500 units. We evaluated the frequency with which the initial fixed dose 4F-PCC was inadequate, as defined by need for supplemental dosing. As part of the protocol, if the initial fixed-dose 4F-PCC is administered and does not achieve INR goal, then the remainder of the standard weight- and INR-based dosing can be given. During the study period, 63 patients on warfarin received 4F-PCC using the fixed-dose protocol. Based on the INR following 4F-PCC administration, 11 patients (17%) were eligible to receive a supplemental dose based on failure to achieve their specified INR goal. Two of the 11 patients eligible for supplemental 4F-PCC dosing received the second dose, both with initial supratherapeutic INRs > 3.5. We found that most patients given an initial fixed-dose 4F-PCC achieved their INR goals, and of those who did not, most did not receive supplemental dosing, suggesting that clinical providers felt that adequate hemostasis had been achieved. In addition, fixed-dose 4F-PCC was able to be given rapidly, with few dosing errors, suggesting that this is a reasonable option for 4F-PCC delivery.

Keywords: Fixed-dose; Four-factor prothrombin complex concentrate; Protocol; Supplemental dosing.

MeSH terms

  • Aged, 80 and over
  • Blood Coagulation Factors / administration & dosage*
  • Body Weight
  • Clinical Protocols
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations*
  • Drug Monitoring / methods
  • Drug-Related Side Effects and Adverse Reactions* / etiology
  • Drug-Related Side Effects and Adverse Reactions* / therapy
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Outcome and Process Assessment, Health Care
  • Retrospective Studies
  • Warfarin / adverse effects*


  • Blood Coagulation Factors
  • prothrombin complex concentrates
  • Warfarin