과도한 항응고 효과에 대한 치료현황 평가 및 이후 치료범위 INR로의 전환을 위한 예후인자 분석 = Evaluation of the excessive anticoagulation therapy and analysis of the clinical predictors for the return of the international normalized ratio (INR) within the therapeutic range

다국어 초록 (Multilingual Abstract)

Warfarin, a widely used oral anticoagulant, has a narrow therapeutic index; the side effect is typically monitored according to the international normalized ratio (INR). While the American College of Chest Physicians (ACCP) has proposed the guidelines for the management of excessive use of warfarin as anticoagulation, few data were published for the patient-specific factors that influence the return of the INR within the therapeutic range after the adjusted warfarin doses. Therefore, the aim of this study is to assess the treatment of excessive anticoagulation and prognostic factors that influence the return of the INR within the therapeutic range after the adjusted warfarin doses. Patients who were on warfarin therapy and were presented with an INR greater than 5.0 from Jan 1, 2007 and May 31, 2010 at Seoul National University Bundang Hospital (SNUBH), were included and observed retrospectively by reviewing electronic medical records (EMRs), such as causes of excessive anticoagulation, treatments, adjusted warfarin maintenance doses, and return of the INR within the therapeutic range after the adjusted warfarin doses. A total of 164 cases in 142 patients were analyzed. Common causes of elevated INR were excessive warfarin dose (17.8 %) and drug interaction (15.5 %). A total of 80.1 % was treated by adjusting warfarin dose, such as hold or reduction, and 67.1 % were treated appropriately according to the ACCP guidelines. Seventy-six cases found to have INR value within the therapeutic range [INR 1.7~3.3] by the adjustment and restarted warfarin therapy with adjusted dosage. However, 69 cases had INR values that were not with the range by the adjustment.
Nineteen cases were excluded by warfarin discontinuation, death or follow up loss. The variables, which were associated with INR values returned within the therapeutic range by warfarin dosage adjustment, were age (P = 0.004), maintenance doses of warfarin (P = 0.004), and reduced % of adjusted dosage of warfarin (P < 0.001). By means of a multiple logistic regression model suggested that prognostic factors are associated with maintenance dosage (odds ratio, 0.47 [Cl, 0.31 to 0.93]), and reduced % of dosage (odds ratio, 1.06 [Cl, 1.01 to 1.12]). Therefore, these observations suggested that patients who take lower weekly maintenance doses of warfarin have to monitor their INR carefully, and, if anticoagulation is excessive, appropriately reduce the doses of warfarin. Furthermore, prospective, randomized trials might help the safety and efficacy management of excessive anticoagulation.

참고문헌 (Reference)

1 이병구, "인공심장판막 치환환자의 Warfarin 용량결정" 대한흉부외과학회 38 (38): 761-772, 2005

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

3 Patriquin C, "Treatment of warfarin-associated coagulopathy with vitamin K" 4 (4): 657-665, 2011

4 Hylek E.M, "Risk factors for intracranial hemorrhage in outpatients taking warfarin" 120 (120): 897-902, 1994

5 Pengo V, "Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation" 4 (4): 739-741, 1993

6 Beyth R.J, "Prospective evaluation of an index for predicting the risk of major bleeding in outpatient treated with warfarin" 2 : 91-99, 1998

7 Kuijer P.M, "Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism" 5 : 457-460, 1999

8 Ansell J, "Pharmacology and management of the vitamin K antagonists, American College of Chest Physicians Evidenced-Based Clinical Practice Guidelines (8th Edition)" 133 : 160-198, 2008

9 Crowther M.A, "Low-dose oral vitamin K reliably reverses overanticoagulation due to warfarin" 79 (79): 1116-1118, 1998

10 Pening-van Beest F.J, "Lifestyle and diet as risk factors for over anticoagulation" 55 : 411-417, 2002

11 Ryan P.J, "Computer control of anticoagulant dose for therapeutic management" 299 (299): 1207-1209, 1989

12 Whitling A.M, "Comparing different routes and doses of phytonidone for reversing excessive anticoagulation" 158 (158): 2136-2140, 1998

13 Hylek E.M, "Clinical Predictors of Prolonged Delay in Return of the International Normalized Ratio to within the Therapeutic Range after Excessive Anticoagulation with warfarin" 135 (135): 393-400, 2001

14 Penning-van Beest F.J, "Characteristics of anticoagulant therapy and comorbidity related to overanticoagulation" 86 (86): 569-574, 2001

15 Aspinall S.L, "Bleeding risk index in an anticoagulation clinic, Assessment by indication and implications for care" 20 (20): 1008-1013, 2005

16 Van der Meer F.J, "Bleeding complications in oral anticoagulant therapy, An analysis of risk factors" 153 : 1557-1562, 1993

17 Landefeld C.S, "Anticoagulantrelated bleeding, Clinical epidemiology, prediction, and prevention" 95 : 315-328, 1993

18 Emily B.D, "Adherence to guidelines for the management of excessive warfarin anticoagulation" 27 : 379-384, 2009

19 Hylek E.M, "Acetaminophen and other risk factors for excessive warfarin anticoagulation" 279 (279): 657-662, 1998

20 Libby E.N, "A survey of oral vitamin K use by anticoagulation clinics" 162 (162): 1893-1896, 2002

21 Fan J, "A retrospective evaluation of vitamin K1 therapy to reverse the anticoagulant effect of warfarin" 23 (23): 1245-1250, 2003