Emergent reversal of vitamin K antagonists: addressing all the factors

Am J Surg. 2016 May;211(5):919-25. doi: 10.1016/j.amjsurg.2016.02.007. Epub 2016 Mar 10.

Abstract

Background: Reversal of warfarin-induced coagulopathy after traumatic injury may be done exclusively with prothrombin complex concentrates (PCCs). No direct comparisons between different PCC regimens exist to guide clinical decision-making. Our institution has used 2 distinct PCC strategies for warfarin reversal; a 3-Factor PCC (Profilnine) combined with activated Factor VII (3F-PCC+rVIIa), and a 4-Factor PCC (Kcentra) given without additional factor supplementation.

Methods: Retrospective review of all PCC administrations to trauma patients with acute bleeding who were taking warfarin before injury. Primary endpoints were international normalized ratio (INR) reduction, in-hospital mortality, and diagnosis of deep venous thrombosis (DVT).

Results: Eighty-seven patients were identified from 2011 to 2015. Fifty-three were treated with 3F-PCC+rVIIa and 34 with 4F-PCC. Patient demographics, injury severity, and presenting laboratory data were similar. The 3F-PCC+rVIIa produced a lower median (IQR) INR postreversal compared with 4F-PCC (.75 (.69, 1.00) vs 1.28 (1.13, 1.36), P<.001). Both regimens were able to obtain an INR lower than 1.5 immediately after administration (3F+rVIIA 93.9% vs 4F 97.1%, P =.51). In the 4F-PCC group, there was a significant decrease in the incidence of DVT (2.9% vs 22.6%), P < .01), and a nonsignificant reduction in mortality (2.9% vs 17.0%, P = .08).

Conclusions: Use of 4F-PCC for warfarin reversal after traumatic hemorrhage is associated with a less severe decrease in INR, a significant reduction in DVT rates and a trend toward reduced mortality when compared with similar patients treated with 3F-PCC+rVIIa.

Keywords: Coagulopathy; Prothrombin complex concentrates; Traumatic hemorrhage; Warfarin.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Coagulation Factors / therapeutic use*
  • Chi-Square Distribution
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Combinations
  • Emergencies
  • Factor IX / therapeutic use*
  • Factor VII / therapeutic use*
  • Factor X / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced*
  • Hemorrhage / complications
  • Hemorrhage / drug therapy*
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Prothrombin / therapeutic use*
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / adverse effects*
  • Warfarin / therapeutic use
  • Wounds and Injuries / complications
  • Wounds and Injuries / diagnosis

Substances

  • Blood Coagulation Factors
  • Drug Combinations
  • Vitamin K
  • prothrombin complex concentrates
  • Warfarin
  • Factor VII
  • Prothrombin
  • Factor IX
  • Factor X
  • Profilnine SD