遗传性血栓形成风险因素与静脉血栓栓塞：在外周深静脉血栓形成和肺栓塞中的不同作用。

Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism.

作者信息

Margaglione M, Brancaccio V, De Lucia D, Martinelli I, Ciampa A, Grandone E, Di Minno G

机构信息

Unita' di Aterosclerosi e Trombos, Istituto di Ricovera e Cura a Carattere Scientifico "Casa Sollievo della Sofferenza," S. Giovanni Rotondo, Italy.

出版信息

Chest. 2000 Nov;118(5):1405-11. doi: 10.1378/chest.118.5.1405.

DOI:10.1378/chest.118.5.1405

PMID:11083693

Abstract

STUDY OBJECTIVES

To investigate whether the FII A(20210) mutation is associated with isolated pulmonary embolism (PE).

DESIGN

Case-control study.

SETTING

Five thrombosis centers in southern Italy.

PATIENTS

Six hundred forty-seven consecutive referred patients with objectively documented venous thrombosis and 1,329 control subjects.

MEASUREMENTS AND RESULTS

Medical histories were collected. The G-to-A transition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to-A transition at nucleotide position 20210 within the prothrombin gene locus (FII A(20210)), levels of anticoagulant factors, and levels of antiphospholipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with additional PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% and 16.6%, respectively) and FII A(20210) mutation (14.2% and 12.6%, respectively), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, respectively). In both groups, the frequencies of FV Leiden and/or FII A(20210) mutation were higher than those observed among 1,329 apparently healthy control subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients with isolated PE (n = 126), prevalences of FV Leiden (7.1%) and FII A(20210) mutation (8.7%) were similar to those of control subjects. Inherited thrombophilic abnormalities were less frequent among patients with PE only (15.6%) than among those with DVT only (37.0%; p < 0.001) or whose conditions were complicated by PE (28. 0%; p = 0.020). Adjusting for age and sex, FV Leiden mutation, FII A(20210) mutation, or both mutations were associated with DVT with PE (FV Leiden mutation: odds ratio [OR], 3.0; 95% confidence interval [CI], 1.6 to 5.5; FII A(20210) mutation: OR, 2.6; 95% CI, 1. 3 to 5.2; and both mutations: OR, 82.1; 95% CI, 7.5 to 901.2) or without PE (FV Leiden mutation: OR, 6.1; 95% CI, 4.0 to 9.3; FII A(20210) mutation: OR, 2.8; 95% CI, 1.7 to 4.8; and both mutations: OR, 167.5; 95% CI, 21.6 to 1,297.7), but not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FII A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 22.1; 95% CI, 1. 3 to 370.2).

CONCLUSIONS

FII A(20210) mutation is associated with DVT in the lower extremities alone or when complicated by PE, but it is not associated with isolated PE.

摘要

研究目的

探讨FII A(20210)突变是否与孤立性肺栓塞（PE）相关。

设计

病例对照研究。

地点

意大利南部的五个血栓形成中心。

患者

647例连续转诊的有客观记录的静脉血栓形成患者和1329名对照受试者。

测量与结果

收集病史。采用标准技术测定凝血因子V基因（FV Leiden）第1691位核苷酸处的G-to-A转换以及凝血酶原基因位点（FII A(20210)）第20210位核苷酸处的G-to-A转换、抗凝因子水平和抗磷脂抗体水平。下肢深静脉血栓形成（DVT）患者（n = 346）或合并PE患者（n = 175）的FV Leiden突变（分别为24.3%和16.6%）和FII A(20210)突变（分别为14.2%和12.6%）患病率相似，天然抗凝剂缺乏情况也相似（分别为4.9%和2.3%）。在两组中，FV Leiden和/或FII A(20210)突变的频率均高于1329名明显健康对照受试者中的观察频率（分别为4.8%和4.4%；p < 0.0001）。在孤立性PE患者（n = 126）中，FV Leiden（7.1%）和FII A(20210)突变（8.7%）的患病率与对照受试者相似。仅患有PE的患者中遗传性血栓形成异常的发生率（15.6%）低于仅患有DVT的患者（37.0%；p < 0.001）或合并PE的患者（28.0%；p = 0.020）。校正年龄和性别后，FV Leiden突变、FII A(20210)突变或两者同时存在与合并PE的DVT相关（FV Leiden突变：比值比[OR]，3.0；95%置信区间[CI]，1.6至5.5；FII A(20210)突变：OR，2.6；95% CI，1.3至5.2；两者同时存在：OR，82.1；95% CI，7.5至901.2）或不合并PE的DVT相关（FV Leiden突变：OR，6.1；95% CI，4.0至9.3；FII A(20210)突变：OR，2.8；95% CI，1.7至4.8；两者同时存在：OR，167.5；95% CI，21.6至1297.7），但与孤立性PE无关（FV Leiden突变：OR，1.2；95% CI，0.5至2.8；FII A(20210)突变：OR，1.2；95% CI，0.5至3.1；两者同时存在：OR，22.1；95% CI，1.3至370.2）。