1.
Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial
Crowther MA, Ageno W, Garcia D, Wang L, Witt DM, Clark NP, Blostein MD, Kahn SR, Vesely SK, Schulman S, et al
Annals of Internal Medicine. 2009;150((5):):293-300.
-
-
Free full text
-
Abstract
BACKGROUND Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain. OBJECTIVE To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy. DESIGN Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment. SETTING 14 anticoagulant therapy clinics in Canada, the United States, and Italy. PATIENTS Nonbleeding patients with INR values of 4.5 to 10.0. INTERVENTION Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed). MEASUREMENTS Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes). RESULTS 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001). LIMITATION Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed. CONCLUSION Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0. FUNDING Canadian Institutes of Health Research and Italian Ministry of Universities and Research.
2.
Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials
Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W
Thrombosis Research. 2009;123((5):):687-96.
Abstract
BACKGROUND Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. METHODS MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P<0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I(2)=0%, P=0.531). CONCLUSIONS We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.