Low-Dose Vitamin K When Starting Warfarin
Low-Dose Vitamin K When Starting Warfarin
Study Objective. To determine the effect of very low-dose subcutaneous vitamin K (SCVK) compared with withholding warfarin for above-target international normalized ratio (INR) values after joint surgery.
Design. Historical controlled study.
Setting. University hospital.
Subjects. One hundred thirty-nine patients beginning warfarin after total joint surgery.
Intervention. For a high INR, warfarin was either withheld or SCVK 100, 300, or 400 µg was administered, depending on INR value.
Measurements and Main Results. The primary outcome was change in INR from the day of intervention (day 1) to the next day (day 2). Adjusting for day 1 INR, the mean day 2 INR was 2.10 (95% confidence interval [CI] 1.86-2.33) after SCVK, compared with 2.73 (95% CI 2.50-2.96) in controls. This corresponded to declines of -0.72 and -0.08, respectively (p=0.001).
Conclusion. In orthopedic patients starting warfarin therapy, very low-dose SCVK was more effective than withholding warfarin in reducing high INRs. Investigations in other populations and assessment of the effect of low-dose SCVK on postoperative bleeding are indicated.
Warfarin is an important agent for primary and secondary prevention of thromboembolic disease; however, concerns about drug-induced bleeding may limit prescriptions of the drug. One of several risk factors for hemorrhage is the intensity of anticoagulation. Several methods have been suggested for managing patients with a high international normalized ratio (INR), such as withholding warfarin until the INR is reduced, administering fresh-frozen plasma, or giving vitamin K.
Vitamin K is an essential cofactor for hepatic production of coagulation factors II, VII, IX, and X. Biologic activity of these clotting factors requires vitamin K-dependent conversion of glutamic acid residues to
-carboxyglutamic acid on the N-terminal region of the proteins. Warfarin exerts its anticoagulant activity by inhibiting vitamin K epoxide reductase and vitamin K reductase, important enzymes of the vitamin K metabolic cycle. Inhibition of these enzymes causes a decrease in
-carboxylation of coagulation factors, resulting in limited ability for vitamin K-dependent coagulation proteins to bind calcium and form a clot. Administering vitamin K reverses warfarin's anticoagulant effect because conversion to the activated form of vitamin K may occur by a warfarin-resistant enzyme pathway.
Studies evaluated the effectiveness of vitamin K to reduce warfarin-induced anticoagulation in patients with an elevated INR. The vitamin was administered intravenously and subcutaneously, with evidence also supporting the oral route. The optimum dose and most effective route of administration for this indication are not known.
Warfarin often is administered to prevent venous thromboembolism (VTE) after hip or knee replacement surgery. In this setting, during which dietary consumption of vitamin K is low, vitamin K deficiency may cause a rapid rise in INR at the start of warfarin therapy. For these patients, an elevated INR is undesirable because of the increased risk of postoperative bleeding complications or wound hematoma. Complete reversal of anticoagulation is also undesirable due to the high risk of VTE after orthopedic surgery. We hypothesized that very low-dose vitamin K would be effective in these patients by reducing the risk of bleeding while balancing the need for effective anticoagulation.
Published studies on this subject are not available. The objective of this study was to determine if very low-dose subcutaneous vitamin K (SCVK) was effective in reversing INRs above target range during start of warfarin therapy in postoperative patients with no active signs or symptoms of bleeding.
Study Objective. To determine the effect of very low-dose subcutaneous vitamin K (SCVK) compared with withholding warfarin for above-target international normalized ratio (INR) values after joint surgery.
Design. Historical controlled study.
Setting. University hospital.
Subjects. One hundred thirty-nine patients beginning warfarin after total joint surgery.
Intervention. For a high INR, warfarin was either withheld or SCVK 100, 300, or 400 µg was administered, depending on INR value.
Measurements and Main Results. The primary outcome was change in INR from the day of intervention (day 1) to the next day (day 2). Adjusting for day 1 INR, the mean day 2 INR was 2.10 (95% confidence interval [CI] 1.86-2.33) after SCVK, compared with 2.73 (95% CI 2.50-2.96) in controls. This corresponded to declines of -0.72 and -0.08, respectively (p=0.001).
Conclusion. In orthopedic patients starting warfarin therapy, very low-dose SCVK was more effective than withholding warfarin in reducing high INRs. Investigations in other populations and assessment of the effect of low-dose SCVK on postoperative bleeding are indicated.
Warfarin is an important agent for primary and secondary prevention of thromboembolic disease; however, concerns about drug-induced bleeding may limit prescriptions of the drug. One of several risk factors for hemorrhage is the intensity of anticoagulation. Several methods have been suggested for managing patients with a high international normalized ratio (INR), such as withholding warfarin until the INR is reduced, administering fresh-frozen plasma, or giving vitamin K.
Vitamin K is an essential cofactor for hepatic production of coagulation factors II, VII, IX, and X. Biologic activity of these clotting factors requires vitamin K-dependent conversion of glutamic acid residues to
-carboxyglutamic acid on the N-terminal region of the proteins. Warfarin exerts its anticoagulant activity by inhibiting vitamin K epoxide reductase and vitamin K reductase, important enzymes of the vitamin K metabolic cycle. Inhibition of these enzymes causes a decrease in
-carboxylation of coagulation factors, resulting in limited ability for vitamin K-dependent coagulation proteins to bind calcium and form a clot. Administering vitamin K reverses warfarin's anticoagulant effect because conversion to the activated form of vitamin K may occur by a warfarin-resistant enzyme pathway.
Studies evaluated the effectiveness of vitamin K to reduce warfarin-induced anticoagulation in patients with an elevated INR. The vitamin was administered intravenously and subcutaneously, with evidence also supporting the oral route. The optimum dose and most effective route of administration for this indication are not known.
Warfarin often is administered to prevent venous thromboembolism (VTE) after hip or knee replacement surgery. In this setting, during which dietary consumption of vitamin K is low, vitamin K deficiency may cause a rapid rise in INR at the start of warfarin therapy. For these patients, an elevated INR is undesirable because of the increased risk of postoperative bleeding complications or wound hematoma. Complete reversal of anticoagulation is also undesirable due to the high risk of VTE after orthopedic surgery. We hypothesized that very low-dose vitamin K would be effective in these patients by reducing the risk of bleeding while balancing the need for effective anticoagulation.
Published studies on this subject are not available. The objective of this study was to determine if very low-dose subcutaneous vitamin K (SCVK) was effective in reversing INRs above target range during start of warfarin therapy in postoperative patients with no active signs or symptoms of bleeding.
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