와파린 복용 중 과도한 INR 상승 시 비출혈 환자에서 비타민 K1 사용의 후향적 평가 = A Retrospective Evaluation of Vitamin K1 Therapy for Managing Supratherapeutic International Normalized Ratio in Non-Bleeding Patients Treated with Warfarin Bi

다국어 초록 (Multilingual Abstract)

Backgrounds : Warfarin, an oral anticoagulant, has narrow therapeutic range. Bleeding risk can rise dramatically in patients with supratherapeutic international normalized ratio (INR).
There are various guidelines for correcting excessive anticoagulation. One of these is the 9th ACCP guideline. It suggests simply holding warfarin in non-bleeding patients with INR value of 4.5 to 10.0.
Therefore, we evaluated the treatment methods for INR control at Seoul National University Hospital (SNUH).
Methods : Patients with INR value of 4.5 to 10.0 without evidence of bleeding who were followed at an anticoagulation clinic in SNUH from September 2012 to August 2014 were included in this study.
They were observed retrospectively based on medical records and anticoagulation clinic sheets.
Patients were divided into two groups: 1) short-term warfarin withdrawal group, and 2) vitamin K1 group. We evaluated the incidence of INR over-correction, bleeding, and thromboembolic events in each group.
Results : Most patients with 4.5 ≤ INR 6.0 were treated by temporarily holding warfarin. Finally, a total of 30 cases with INR value of 6.0 to 10.0 were analyzed, including 13 cases treated by temporarily holding warfarin and 17 cases treated by vitamin K1. INR over-correction was more frequent in the vitamin K1 group (11 cases (64.7%) in the vitamin K1 group vs. 1 case (7.7%) in the temporary warfarin withdrawal group, p=0.002). We found no significant difference in bleeding rate between the two treatment groups (minor bleeding in 1 case (7.7%) in the temporary warfarin withdrawal group and 1 case (5.9%) in the vitamin K1 group, p=0.687). There was no thromboembolic event or major bleeding in either group.
Conclusion : Considering the risk of thromboembolism by INR over-correction, temporary warfarin withdrawal may be more appropriate than using vitamin K1 for non-bleeding patients with supratherapeutic INR without indications of acute reversal of excessive anticoagulation.

참고문헌 (Reference)

1 전혜영, "Warfarin에 의한 과도한 항응고 효과의 치료현황 평가" 한국병원약사회 26 (26): 66-77, 2009

2 DeZee K. D., "Treatment of excessive anticoagulation with phytonadione (vitamin K)" 166 : 391-397, 2006

3 Dentali F., "Treatment of coumarin-associated coagulopathy:a systematic review and proposed treatment algorithms" 4 : 1853-1863, 2006

4 Demirkan K., "Response to warfarin and other oral anticoagulants: effects of disease states" 93 (93): 448-454, 2000

5 Patel R. J., "Randomized, placebocontrolled trial of oral phytonadione for excessive anticoagulation" 20 (20): 1159-1166, 2000

6 Ansell J., "Pharmacology and Management of the vitamin K antagonist, American College of Chest Practice Guidelines" 133 : 160-198, 2008

7 Crowther M.A., "Oral vitamin K Versus Placebo to Correct Excessive Anticoagulation In Patients Receiving Warfarin" 150 : 293-300, 2009

8 Hirsh J., "Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range" 119 : 8S-21S, 2001

9 "International Society on Thrombosis and Haemostasis, Inc."

10 Rose A. J., "Epidemiology of subtherapeutic anticoagulation in the United States" 2 : 591-597, 2009

11 Denas G., "Effectiveness and safety of a management protocol to correct over-anticoagulation with oral vitamin K : a retrospective study of 1043 cases" 27 : 340-347, 2009

12 Palareti G., "Bleeding complications of oral anticoagulant treatment : an inception-cohort, prospective collaborative study(ISCOAT)" 348 : 423-428, 1996

13 Holbrook A., "Antithrombotic therapy and prevention of thrombosis, American College of Chest, Physicians Evidence-Based Clinical Practice Guidelines" 141 (141): e152s-e184s, 2012

14 Fiore LD, "Anaphylactoid reactions to vitamin" 11 : 175-183, 2001

15 "American Hospital Formulary Service (AHFS)"

16 Watson H. G., "A comparison of the efficacy and rate of response to oral and intravenous vitamin K in reversal of overanticoagulation with warfarin" 115 : 145-149, 2001