title: Associations of thrombophilia, hypofibrinolysis, and retinal vein occlusion.
abstract: We prospectively assessed whether thrombophilia and hypofibrinolysis, amplified by thrombophilic hormone replacement therapy (HRT), were associated with retinal vein occlusion (RVO). We studied 44 cases (18 men, 26 women), > or = 3 months after RVO, 42 with central RVO, 2 with branch RVO, in the consecutive order of their referral by 2 community-based ophthalmologists. PCR and serologic coagulation assays were compared to 83 and 40 healthy adult normal controls, respectively. The 4G allele frequency of the plasminogen activator inhibitor-1 (PAI-1) gene, associated with hypofibrinolysis, was 56 of 88 (64%) in cases vs 79 of 166 (48%) in controls, X(2) = 5.95, p = .015. The PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx), was higher in cases than controls (age-race-sex- adjusted mean 12.2 U/mL vs 6.3, p = .013). By stepwise logistic regression, the PAI-1 gene 4G allele was associated with RVO, odds ratio 1.94, 95% CI 1.12-3.34, p = .018. Thrombophilic resistance to activated protein C (RAPC) was present in 6 of 32 (19%) of cases vs 0 of 40 (0%) controls, Fisher's p [p(f)] = .006. Thrombophilic high factor VIII (> 150%) was present in 3 of 30 (10%) cases vs 0 of 40 (0%) controls, p = .041, p(f) = .07. Comparing 23 RVO cases < or = age 55 and controls < or = age 55 (n = 44 for PCR, n = 40 for serologic measures), RAPC was present in 17% of cases vs 0% controls (p(f) = .026), high Factor VIII in 17% vs 0% (p(f) = .026), heterozygosity for the G1691A Factor V Leiden mutation in 13% vs 2% (p(f) = 0.11), and the 4G allele frequency of the PAI-1 gene 74% vs 39% (p = .0001). PAI-Fx was higher in cases than controls (age-race-sex adjusted mean 12.7 U/mL vs 6.7, p = .016). The case-control odds ratio for the PAI-1 4G allele was 5.54, 95% CI = 1.86-16.7, p = .002. Of the 26 women, 9 (35%) took HRT; 4 of the 9 had PAI-1 gene 4G4G homozygosity, 2 had thrombophilic high anticardiolipin antibody (IgG), 1 was heterozygous for the G1691A Factor V Leiden mutation, and 2 were heterozygous for the thrombophilic PL A1/A2 mutation of the platelet glycoprotein IIb/IIIa gene. Associations between heritable coagulation disorders and RVO, most marked in cases < or = age 55, and often amplified in women by thrombophilic HRT, are, speculatively, causal.
authors.affiliation: Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA. glueckch@healthall.com
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Howard
authors.initials: H
authors.lastname: Bell
authors.forename: Venkat
authors.initials: V
authors.lastname: Rangaraj
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000473:pathology; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000235:genetics / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D011486:Protein C