Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA.
Thromb J. 2011 Oct 10;9:14. doi: 10.1186/1477-9560-9-14.
Patients who receive highly variable doses of warfarin may be at risk for poor anticoagulation control and adverse events. However, we lack a system to identify patients with the highest dose variability. Our objectives were to develop a scoring system to identify patients with high dose variability, and to validate this new measure by demonstrating that patients so identified have poor anticoagulation control and higher rates of adverse events (criterion validity).
We used a database of over 4, 000 patients who received oral anticoagulation in community practice between 2000-2002. We reviewed the charts of 168 patients with large warfarin dose variation and agreed on 18 risk factor definitions for high dose variability. We identified 109 patients with the highest dose variability (cases), as measured by coefficient of variation (CoV, SD/mean). We matched each case to two controls with low dose variability. Then, we examined all 327 charts, blinded to case/control status, to identify the presence or absence of the 18 risk factors for dose variability. We performed a multivariable analysis to identify independent predictors of high CoV. We also compared anticoagulation control, as measured by percent time in therapeutic range (TTR), and rates of adverse events between groups.
CoV corresponded with other measures of anticoagulation control. TTR was 53% among cases and 79% among controls (p < 0.001). CoV also predicted adverse events. Six cases experienced a major hemorrhage versus 1 control (p < 0.001) and 3 cases had a thromboembolic event versus 0 control patients (p = 0.04). Independent predictors of high dose variability included hospitalization (OR = 21.3), decreased oral intake (OR = 12.2), use of systemic steroids (OR = 6.1), acetaminophen (OR = 4.0) and antibiotics (OR = 2.7; p < 0.05 for all).
CoV can be used to identify patients at risk for poor anticoagulation control and adverse events. This new measure has the potential to identify patients at high risk before they suffer adverse events.
接受华法林剂量高度变化的患者可能存在抗凝控制不良和不良事件的风险。然而，我们缺乏识别剂量变化最大患者的系统。我们的目标是开发一种评分系统来识别剂量变化最大的患者，并通过证明如此识别的患者抗凝控制不良和不良事件发生率更高来验证这种新的方法（标准效度）。
我们使用了一个包含 2000-2002 年在社区实践中接受口服抗凝治疗的 4000 多名患者的数据库。我们审查了 168 名华法林剂量变化较大患者的病历，并就 18 个高剂量变化风险因素的定义达成一致。我们确定了 109 名剂量变化最大的患者（病例），以变异系数（SD/均值）衡量。我们将每个病例与两个剂量变化较小的对照进行匹配。然后，我们在不了解病例/对照状态的情况下，对所有 327 份病历进行检查，以确定是否存在或不存在 18 个剂量变化风险因素。我们进行了多变量分析，以确定高变异系数的独立预测因素。我们还比较了两组患者的抗凝控制情况，以治疗范围内的时间百分比（TTR）衡量，以及不良事件的发生率。
变异系数与其他抗凝控制措施相对应。病例组的 TTR 为 53%，对照组为 79%（p <0.001）。变异系数也预测了不良事件。6 例发生大出血，而对照仅 1 例（p <0.001），3 例发生血栓栓塞事件，而对照无（p = 0.04）。高剂量变化的独立预测因素包括住院（OR = 21.3）、口服摄入减少（OR = 12.2）、使用全身皮质类固醇（OR = 6.1）、对乙酰氨基酚（OR = 4.0）和抗生素（OR = 2.7；所有 p<0.05）。
变异系数可用于识别抗凝控制不良和不良事件风险较高的患者。这种新的方法有可能在患者发生不良事件之前识别出高危患者。
