Simioni P, Prandoni P, Lensing A W, Scudeller A, Sardella C, Prins M H, Villalta S, Dazzi F, Girolami A
Institute of Medical Semeiotics, University Hospital of Padua, Italy.
N Engl J Med. 1997 Feb 6;336(6):399-403. doi: 10.1056/NEJM199702063360602.
A recently discovered mutation in coagulation factor V (Arg506-->Gln, referred to as factor V Leiden), which results in resistance to activated protein C, is found in approximately one fifth of patients with venous thromboembolism. However, the risk of recurrent thromboembolism in heterozygous carriers of this genetic abnormality is unknown.
We searched for factor V Leiden in 251 unselected patients with a first episode of symptomatic deep-vein thrombosis diagnosed by venography. The patients were followed prospectively for a mean of 3.9 years to determine the frequency of recurrent venous thrombosis and pulmonary embolism.
Factor V Leiden was found in 41 of the patients (16.3 percent; 95 percent confidence interval, 11.8 to 20.9 percent). The cumulative incidence of recurrent venous thromboembolism after follow-up of up to eight years was 39.7 percent (95 percent confidence interval, 22.8 to 56.5 percent) among carriers of the mutation, as compared with 18.3 percent (95 percent confidence interval, 12.3 to 24.3 percent) among patients without the mutation (hazard ratio, 2.4; 95 percent confidence interval, 1.3 to 4.5; P<0.01).
The risk of recurrent thromboembolic events is significantly higher in carriers of factor V Leiden than in patients without this abnormality. Large trials assessing the risk-benefit ratio of long-term anticoagulation in carriers of the mutation who have had a first episode of venous thromboembolism are indicated.
最近在凝血因子V中发现了一种突变（精氨酸506→谷氨酰胺，称为因子V莱顿突变），该突变导致对活化蛋白C产生抗性，在大约五分之一的静脉血栓栓塞患者中可检测到。然而，这种基因异常的杂合子携带者发生复发性血栓栓塞的风险尚不清楚。
我们在251例经静脉造影诊断为首次出现症状性深静脉血栓形成的未选择患者中检测因子V莱顿突变。对这些患者进行了平均3.9年的前瞻性随访，以确定复发性静脉血栓形成和肺栓塞的发生率。
41例患者（16.3%；95%置信区间为11.8%至20.9%）检测到因子V莱顿突变。在长达八年的随访后，突变携带者中复发性静脉血栓栓塞的累积发生率为39.7%（95%置信区间为22.8%至56.5%），而未发生突变的患者中这一比例为18.3%（95%置信区间为12.3%至24.3%）（风险比为2.4；95%置信区间为1.3至4.5；P<0.01）。
因子V莱顿突变携带者发生复发性血栓栓塞事件的风险显著高于无此异常的患者。有必要进行大型试验，以评估首次发生静脉血栓栓塞的突变携带者长期抗凝治疗的风险效益比。
