Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione

Arch Intern Med. 1999 Dec 13-27;159(22):2721-4. doi: 10.1001/archinte.159.22.2721.


Background: Excessive anticoagulation increases the risk of hemorrhagic complications associated with oral anticoagulant therapy. Oral or parenteral phytonadione is used to reverse excessive anticoagulation. Intravenous (IV) phytonadione, while effective, is associated with a small risk of serious anaphylactic reactions. Subcutaneous (SC) administration is safer, but there is little information on its relative efficacy in small doses.

Methods: Twenty-two patients with asymptomatic prolongation of prothrombin time were prospectively randomized and treated with 1 mg of phytonadione IV or 1 mg SC. Prothrombin time was measured at baseline and at 8 and 24 hours after phytonadione administration and expressed as international normalized ratio (INR).

Results: Mean INR at baseline was 8.0 and 8.5 in the IV and SC groups, respectively (P = .70). At 8 hours, mean INR was 4.6 in the IV group and 8.0 in the SC group (P = .006), and at 24 hours, mean INR was 3.1 in the IV group and 5.0 in the SC group (P = .009). Mean decrease in INR 8 hours after administration of phytonadione was 3.4 in the IV group and 0.4 in the SC group (P = .02), and mean decrease in INR after 24 hours was 4.9 in the IV group and 3.4 in the SC group (P = .18).

Conclusions: For patients who are excessively anticoagulated with warfarin, small doses of SC phytonadione may not correct the INR as rapidly or as effectively as when administered IV. Higher doses must be considered for more rapid and complete reversal of anticoagulation by the SC route.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Anticoagulants / antagonists & inhibitors*
  • Anticoagulants / therapeutic use
  • Antifibrinolytic Agents / administration & dosage*
  • Antifibrinolytic Agents / therapeutic use
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Prospective Studies
  • Prothrombin Time
  • Single-Blind Method
  • Time Factors
  • Vitamin K 1 / administration & dosage*
  • Vitamin K 1 / therapeutic use
  • Warfarin / antagonists & inhibitors*
  • Warfarin / therapeutic use


  • Anticoagulants
  • Antifibrinolytic Agents
  • Warfarin
  • Vitamin K 1