遗传性血栓形成倾向与纤维蛋白溶解功能减退。视网膜静脉阻塞的可能病因。

Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion.

作者信息

Glueck C J, Bell H, Vadlamani L, Gupta A, Fontaine R N, Wang P, Stroop D, Gruppo R

机构信息

Cholesterol Center, Jewish Hospital, Cincinnati, Ohio, USA.

出版信息

Arch Ophthalmol. 1999 Jan;117(1):43-9. doi: 10.1001/archopht.117.1.43.

DOI:10.1001/archopht.117.1.43

PMID:9930159

Abstract

OBJECTIVE

To determine whether heritable thrombophilia and hypofibrinolysis were risk factors for retinal vein occlusion.

DESIGN

Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain reaction assays were performed for 3 thrombophilic gene mutations (factor V Leiden, methylenetetra-hydrofolate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activator inhibitor activity, and polymerase chain reaction analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation measures were performed in 17 patients with retinal vein occlusions with comparison with serologic coagulation measures and polymerase chain reaction assays in 40 and 234 healthy normal volunteers as controls, respectively.

RESULTS

Of 14 patients with retinal vein occlusion with measures of dilute Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6 (43%) had abnormal results (> 38.8 seconds) compared with 1 (3%) of 30 controls (P = .002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233 controls (P = .02). Of 17 patients with vein occlusion, 2 (12%) had normal alleles (5G/5G) for the plasminogen activator inhibitor gene promoter; the other 15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism (P = .03). Patients with vein occlusion were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity. These levels were high (> 22 U/L) in 6 (38%) of 16 patients with vein occlusion compared with 1 (2%) of 40 controls (chi 2 = 12.8; P = .001). Patients with vein occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic Lp(a) (> 35 mg/dL) than controls (5/40 [13%]; chi 2 = 9; P = .003). The median Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62 mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype (P = .05).

CONCLUSION

Thrombophilia and hypofibrinolysis are possible causes of retinal vein occlusion.

摘要

目的

确定遗传性血栓形成倾向和纤维蛋白溶解功能减退是否为视网膜静脉阻塞的危险因素。

设计

血栓形成倾向（血栓形成可能性增加）的检测指标包括抗心磷脂抗体（IgG和IgM）、狼疮抗凝物（包括稀释蝰蛇毒凝血时间）、抗原性蛋白C和S以及同型半胱氨酸。对3种血栓形成倾向相关基因突变（因子V莱顿突变、亚甲基四氢叶酸还原酶和凝血酶原基因突变）进行聚合酶链反应检测。纤维蛋白溶解功能减退（溶解血栓能力降低）的检测指标包括脂蛋白Lp(a)、纤溶酶原激活物抑制剂活性以及对PAI1基因纤溶酶原激活物抑制剂4G/5G多态性的聚合酶链反应分析。对17例视网膜静脉阻塞患者进行这些凝血指标检测，并分别与40例和234例健康正常志愿者的血清学凝血指标检测及聚合酶链反应检测结果进行比较，后者作为对照。

结果

在14例接受稀释蝰蛇毒凝血时间检测的视网膜静脉阻塞患者中，6例（43%）存在血栓形成倾向抗磷脂抗体检测结果异常（>38.8秒），而30例对照中仅有1例（3%）异常（P = 0.002）。在17例静脉阻塞患者中，3例（18%）为血栓形成倾向因子V莱顿G1691A突变杂合子，而233例对照中有7例（3%）为杂合子（P = 0.02）。在17例静脉阻塞患者中，2例（12%）纤溶酶原激活物抑制剂基因启动子具有正常等位基因（5G/5G）；其他15例（88%）为与纤维蛋白溶解功能减退相关的4G多态性杂合子或纯合子。在234例对照中，85例（36.3%）具有5G/5G等位基因；149例（63.7%）为4G多态性杂合子或纯合子（P = 0.03）。静脉阻塞患者更易出现纤维蛋白溶解功能减退的主要决定因素——纤溶酶原激活物抑制剂活性升高。16例静脉阻塞患者中有6例（38%）该指标水平较高（>22 U/L），而40例对照中仅有1例（2%）升高（χ2 = 12.8；P = 0.001）。静脉阻塞患者比对照更易出现纤维蛋白溶解功能减退的Lp(a)水平升高（>35 mg/dL）（8/16 [50%]比5/40 [13%]；χ2 = 9；P = 0.003）。具有4G/4G基因型的静脉阻塞患者Lp(a)水平中位数为62 mg/dL，而具有4G/4G基因型的对照患者为5.3 mg/dL（P = 0.05）。