Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter?

Thromb Res. 2012 Dec;130(6):833-40. doi: 10.1016/j.thromres.2012.10.001. Epub 2012 Nov 6.


Introduction: Prothrombin complex concentrates are used for rapid reversal of vitamin K antagonists in patients with bleeding or those requiring surgery or invasive procedures. Current guidelines suggest 4-factor products are preferred over 3-factor prothrombin complex concentrates.

Materials and methods: We performed a systematic review comparing the effectiveness of 3-factor to 4-factor prothrombin complex concentrates in normalizing the international normalized ratio to ≤ 1.5 in patients with acquired coagulopathy due to vitamin K antagonist use. Studies reporting administration of prothrombin complex concentrates for emergent reversal of vitamin K antagonists that included results of baseline prothrombin time/international normalized ratio and follow-up testing within 60 minutes of prothrombin complex concentrates administration were included.

Results: A total of 18 studies were included representing 654 patients. The most common indications for prothrombin complex concentrate were intracerebral hemorrhage, urgent surgery or invasive procedure, and gastrointestinal bleeding. Baseline international normalized ratio values ranged from 3.3-5.1 in the 3-factor group and from 2.3 to greater than 20 in the 4-factor group. The international normalized ratio repeated within one hour of prothrombin complex concentrates administration ranged from 1.2-1.9 in the 3-factor group and 1.0-1.9 in the 4-factor group. International normalized ratio decreased to ≤ 1.5 within one hour after prothrombin complex concentrates administration in 6 of 9 studies in the 3-factor group, and 12 of 13 studies in the 4-factor group.

Conclusion: More reliable correction of the international normalized ratio was seen with 4-factor compared to 3-factor prothrombin complex concentrates which may have clinical implications since 4-factor products are unavailable in some countries.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / antagonists & inhibitors*
  • Blood Coagulation Factors / administration & dosage*
  • Drug Interactions
  • Humans
  • International Normalized Ratio
  • Middle Aged
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage
  • Warfarin / antagonists & inhibitors*
  • Young Adult


  • Anticoagulants
  • Blood Coagulation Factors
  • Vitamin K
  • prothrombin complex concentrates
  • Warfarin