Heritable thrombophilia and hypofibrinolysis - Possible causes of retinal vein occlusion

Objective: To determine whether heritable thrombophilia and hypofibrinolysi s were risk factors for retinal vein occlusion. Design: Measures of thrombophilia (increased likelihood of thrombus formati on) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagul ant (including dilute Russell viper venom clotting time), antigenic protein s C and S, and homocysteine. Polymerase chain reaction assays were performe d for 3 thrombophilic gene mutations (factor V Leiden, methylenetetrahydrof olate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduc ed ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activat or inhibitor activity, and polymerase chain reaction analysis of the hypofi brinolytic 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 antibo dy, 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 heter ozygous 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 pol ymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 ( 36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous fo r the 4G polymorphism (P=.03). Patients with vein occlusion were more likel y to have high levels of the major determinant of hypofibrinolysis, plasmin ogen activator inhibitor activity. These levels were high (>22 U/L) in 6 (3 8%) 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 co ntrols (5/40 [13%]; chi(2) = 9; P =.003). The median Lp(a) level in patient s 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 retin al vein occlusion.