Fihn S D, Callahan C M, Martin D C, McDonell M B, Henikoff J G, White R H
Northwest Veterans Affairs Health Services Research and Development Field Program (152), Veterans Affairs Puget Sound Healthcare System, Seattle, WA 98108, USA.
Ann Intern Med. 1996 Jun 1;124(11):970-9. doi: 10.7326/0003-4819-124-11-199606010-00004.
To determine whether increasing age is associated with an increased risk for bleeding during warfarin treatment.
Combined retrospective and prospective cohort studies.
6 anticoagulation clinics.
2376 patients receiving warfarin for various indications.
Bleeding events categorized as minor (resulting in no costs or consequences), serious (requiring testing or treatment), life-threatening, or fatal.
812 first bleeding events (4 fatal, 33 life-threatening, 222 serious, and 553 minor) occurred during 3702 patient-years. Age was inversely related to the mean warfarin dose and dose-adjusted prothrombin time ratio. The unadjusted incidence of minor bleeding complications did not vary according to age group: 18.0 per 100 patient-years for patients younger than 50 years of age, 21.5 for patients 50 to 59 years of age, 24.0 for patients 60 to 69 years of age; 23.5 for patients 70 to 79 years of age, and 16.3 for patient 80 years of age and older. The unadjusted incidence of serious bleeding complications also did not vary according to age group: 9.3 per 100 patient-years for patients younger than 50 years of age, 7.1 for patients 50 to 59 years of age, 6.6 for patients 60 to 69 years of age, 5.1 for patients 70 to 79 years of age, and 4.4 for patients 80 years of age and older. The unadjusted incidence of life-threatening or fatal complications combined was significantly higher among the oldest patients: 0.75 per 100 patient-years for patients younger than 50 years of age, 0.97 for patients 50 to 59 years of age, 1.10 for patients 60 to 69 years of age, 0.68 for patients 70 to 79 years of age, and 3.38 for patients 80 years of age and older. Patients 80 years of age and older had a relative risk of 4.5 (95% CI, 1.3 to 15.6) compared with patients younger than 50 years of age. After adjustment for the intensity of anticoagulation therapy and the deviation in the prothrombin time ratio using Cox and Poisson regression, age was not generally associated with the occurrence of bleeding; relative risk estimates ranged from 0.99 to 1.03 per year of age (lower-bound 95% CI, 0.97 to 1.01; upper-bound 95% CI, 1.00 to 1.09). The single exception was life-threatening and fatal complications in patients 80 years of age or older (relative risk, 4.6 [CI, 1.2 to 18.1]).
Age did not appear to be an important determinant of risk for bleeding in patients receiving warfarin, with the possible exception of age 80 years or older. The intensity of anticoagulation therapy and the deviation in the prothrombin time ratio were much stronger predictors of risk for bleeding.
确定年龄增长是否与华法林治疗期间出血风险增加相关。
回顾性和前瞻性队列研究相结合。
6家抗凝门诊。
2376例因各种适应证接受华法林治疗的患者。
出血事件分为轻微（无费用或后果）、严重（需要检查或治疗）、危及生命或致命。
在3702患者年期间发生了812例首次出血事件（4例致命、33例危及生命、222例严重和553例轻微）。年龄与平均华法林剂量和剂量调整后的凝血酶原时间比值呈负相关。轻微出血并发症的未调整发病率在各年龄组中无差异：年龄小于50岁的患者为每100患者年18.0例，50至59岁的患者为21.5例，60至69岁的患者为24.0例，70至79岁的患者为23.5例，80岁及以上的患者为16.3例。严重出血并发症的未调整发病率在各年龄组中也无差异：年龄小于50岁的患者为每100患者年9.3例，50至59岁的患者为7.1例，60至69岁的患者为6.6例，70至79岁的患者为5.1例，80岁及以上的患者为4.4例。危及生命或致命并发症合并的未调整发病率在年龄最大的患者中显著更高：年龄小于50岁的患者为每100患者年0.75例，50至59岁的患者为0.97例，60至69岁的患者为1.10例，70至79岁的患者为0.68例，80岁及以上的患者为3.38例。与年龄小于50岁的患者相比，80岁及以上的患者相对风险为4.5（95%可信区间，1.3至15.6）。在使用Cox和泊松回归对抗凝治疗强度和凝血酶原时间比值偏差进行调整后，年龄一般与出血发生无关；每年年龄的相对风险估计范围为0.99至1.03（下限95%可信区间，0.97至1.01；上限95%可信区间，1.00至1.09）。唯一的例外是80岁及以上患者的危及生命和致命并发症（相对风险，4.6[可信区间，1.2至18.1]）。
年龄似乎不是接受华法林治疗患者出血风险的重要决定因素，80岁及以上可能除外。抗凝治疗强度和凝血酶原时间比值偏差是出血风险更强的预测因素。
