White R H, McKittrick T, Takakuwa J, Callahan C, McDonell M, Fihn S
Division of General Medicine, University of California, Davis, Sacramento.
Arch Intern Med. 1996 Jun 10;156(11):1197-201.
The incidence of explicity defined life-threatening bleeding during warfarin sodium therapy is largely unknown, as are the prognosis for and treatment of patients who have such bleeding. In addition, the location of the source of the life-threatening bleeding and the risk factors associated with life-threatening bleeding are not well-defined.
To determine the incidence of explicitly defined life-threatening bleeding during warfarin therapy, to identify the site of bleeding, to determine the risk factors for life-threatening bleeding, and to determine the risk of subsequent bleeding among patients receiving warfarin therapy.
A cross-sectional prevalence study was conducted and data were combined with those obtained during prospective observation of a dynamic cohort of patients followed up in 2 university-affiliated and 3 Veterans Administration anticoagulation clinics.
For this study, 1999 patients were followed up for 3865 patient-years; 32 patients (11 women, 21 men, mean age of 60 years) met criteria for life-threatening bleeding, an incidence of 0.83 events/100 patient-years (95% confidence interval, 0.54-1.12). The most common indication for warfarin was to prevent thromboembolism because the patient had a mechanical heart valve (17/32 patients, 53%). The gastrointestinal tract was the definite or likely site of bleeding in 21 (66%) of the 32 patients. The prothrombin time ratio was longer than 2.0 or the international normalized ratio was longer than 4.5 in 16 (55%) of the 29 patients in whom a coagulation time was measured. Fourteen (44%) of the 32 patients had a history of peptic ulcer disease or gastrointestinal bleeding. Warfarin was restarted in 26 (81%) of the 32 patients. Twenty-five of 26 patients were followed up for a median of 30 months (range, 5-143 months); 14 (56%) of the 25 patients had a subsequent bleeding event, with 8 (57%) of the 14 having 1 or more additional life-threatening bleeding events (1 fatal) after a median of 11.5 months (range, 0.5-22 months).
We conclude that in this cohort: (1) the incidence of life-threatening bleeding was rare, (2) the gastrointestinal tract was the site of bleeding in two thirds of the patients who experienced life-threatening bleeding, (3) most patients who experienced life-threatening bleeding had multiple risk factors for bleeding, including excessive anticoagulation, and (4) the risk of subsequent bleeding was extremely high among the patients who continued to receive warfarin therapy.
华法林钠治疗期间明确界定的危及生命出血的发生率很大程度上未知，此类出血患者的预后及治疗情况同样如此。此外，危及生命出血的出血源位置以及与之相关的危险因素尚不明确。
确定华法林治疗期间明确界定的危及生命出血的发生率，确定出血部位，确定危及生命出血的危险因素，并确定接受华法林治疗患者后续出血的风险。
进行了一项横断面患病率研究，并将数据与在2家大学附属医院和3家退伍军人管理局抗凝门诊对一个动态队列患者进行前瞻性观察期间获得的数据相结合。
在本研究中，1999例患者接受了3865患者年的随访；32例患者（11例女性，21例男性，平均年龄60岁）符合危及生命出血的标准，发生率为0.83事件/100患者年（95%置信区间，0.54 - 1.12）。华法林最常见的适应证是预防血栓栓塞，因为患者有机械心脏瓣膜（17/32例患者，53%）。32例患者中有21例（66%）的胃肠道是明确或可能的出血部位。在测定凝血时间的29例患者中，16例（55%）的凝血酶原时间比值大于2.0或国际标准化比值大于4.5。32例患者中有14例（44%）有消化性溃疡病或胃肠道出血史。32例患者中有26例（81%）重新开始使用华法林。26例患者中有25例接受了中位30个月（范围5 - 143个月）的随访；25例患者中有14例（56%）发生了后续出血事件，14例中有8例（57%）在中位11.5个月（范围0.5 - 22个月）后发生了1次或更多次额外的危及生命出血事件（1例死亡）。
我们得出结论，在这个队列中：（1）危及生命出血的发生率很低，（2）胃肠道是三分之二发生危及生命出血患者的出血部位，（3）大多数发生危及生命出血的患者有多种出血危险因素，包括抗凝过度，（4）继续接受华法林治疗的患者后续出血风险极高。
