Hylek E M, Heiman H, Skates S J, Sheehan M A, Singer D E
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
JAMA. 1998 Mar 4;279(9):657-62. doi: 10.1001/jama.279.9.657.
Warfarin is highly effective in preventing thromboembolism, but increases the risk of hemorrhage, particularly at an international normalized ratio (INR) greater than 4.0. Identifying causes of excessive anticoagulation in clinical practice could help target patients at risk for elevated INRs.
To determine causes of INRs greater than 6.0 in a clinical practice setting.
Case-control study.
Outpatient anticoagulant therapy unit.
Outpatients followed up prospectively from April 1995 to March 1996 who had been taking warfarin for more than 1 month, had a target INR of 2.0 to 3.0, and were able to be interviewed within 24 hours of their reported INR. Case patients had INRs greater than 6.0; controls were randomly selected from patients having INRs between 1.7 and 3.3.
Factors associated with INRs greater than 6.0, including medication use, recent diet, illness, alcohol consumption, and actual warfarin use.
A total of 93 cases and 196 controls were interviewed; they did not differ in age, indication for warfarin, length of therapy, warfarin dose, number of prescription medications, or previous INR or long-term INR variability. Acetaminophen ingestion was independently associated in a dose-dependent manner with having an INR greater than 6.0 (P for trend <.001). For the highest-dose category of acetaminophen intake, 9100 mg/wk or more, the odds of having an INR greater than 6.0 were increased 10-fold (95% confidence interval [CI], 2.6-37.9). Other factors independently associated with an INR greater than 6.0 were new medication known to potentiate warfarin (odds ratio [OR], 8.5; 95% CI, 2.9-24.7), advanced malignancy (OR, 16.4; 95% CI, 2.4-111.0), recent diarrheal illness (OR, 3.5; 95% CI,1.4-8.6), decreased oral intake (OR, 3.6; 95% CI, 1.3-9.7), and taking more warfarin than prescribed (OR, 8.1; 95% CI, 2.2-30.0). Higher vitamin K intake (OR, 0.7; 95% CI, 0.5-0.9) and habitual alcohol consumption of from 1 drink every other day to 2 drinks a day (OR, 0.2; 95% CI, 0.1-0.7) were associated with decreased risk.
These data suggest that acetaminophen is an underrecognized cause of overanticoagulation in the outpatient setting. Several other clinically important risk factors were identified. Increased monitoring of INR values when such risk factors are present or modification of the risk factors themselves should reduce the frequency of dangerously high levels of anticoagulation.
华法林在预防血栓栓塞方面非常有效，但会增加出血风险，尤其是国际标准化比值（INR）大于4.0时。在临床实践中识别过度抗凝的原因有助于确定INR升高风险的患者。
确定临床实践中INR大于6.0的原因。
病例对照研究。
门诊抗凝治疗单元。
1995年4月至1996年3月期间接受前瞻性随访的门诊患者，他们服用华法林超过1个月，目标INR为2.0至3.0，并且在报告INR后24小时内能够接受访谈。病例组患者INR大于6.0；对照组从INR在1.7至3.3之间的患者中随机选择。
与INR大于6.0相关的因素，包括药物使用、近期饮食、疾病、酒精摄入和实际华法林使用情况。
共访谈了93例病例和196例对照；他们在年龄、华法林适应证、治疗时长、华法林剂量、处方药数量、既往INR或长期INR变异性方面无差异。对乙酰氨基酚摄入以剂量依赖方式独立与INR大于6.0相关（趋势P值<.001）。对于对乙酰氨基酚摄入最高剂量类别，即每周9100毫克或更多，INR大于6.0的几率增加了10倍（95%置信区间[CI]，2.6 - 37.9）。其他与INR大于6.0独立相关的因素包括已知会增强华法林作用的新药（比值比[OR]，8.5；95%CI，2.9 - 24.7）、晚期恶性肿瘤（OR，16.4；95%CI，2.4 - 111.0）、近期腹泻病（OR，3.5；95%CI，1.4 - 8.6）、口服摄入量减少（OR，3.6；95%CI，1.3 - 9.7）以及服用华法林超过规定剂量（OR，8.1；95%CI，2.2 - 30.0）。较高的维生素K摄入量（OR，0.7；95%CI，0.5 - 0.9）和每隔一天饮用1杯至每天饮用2杯的习惯性酒精摄入（OR，0.2；95%CI，0.1 - 0.7）与风险降低相关。
这些数据表明，对乙酰氨基酚是门诊环境中未被充分认识的过度抗凝原因。还确定了其他几个临床重要的风险因素。当存在此类风险因素时增加对INR值的监测或对风险因素本身进行调整应能降低危险的高抗凝水平的发生频率。
